WebMD Public Information from the National Cancer Institute Last Updated: October 07, 2011

General Information About Vaginal Cancer

Vaginal cancer is a disease in which malignant (cancer) cells form in the vagina. The vagina is the canal leading from the cervix (the opening of uterus) to the outside of the body. At birth, a baby passes out of the body through the vagina (also called the birth canal). Anatomy of the female reproductive system. The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium. Vaginal cancer is not common. When found in early stages, it can often be cured. There are two main types of vaginal cancer:

Squamous cell carcinoma: Cancer that forms in squamous cells, the thin, flat cells lining the vagina. Squamous cell vaginal cancer spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer. It is found most often in women aged 60 or older. Adenocarcinoma: Cancer that begins in glandular (secretory) cells. Glandular cells in the lining of the vagina make and release fluids such as mucus. Adenocarcinoma is more likely than squamous cell cancer to spread to the lungs and lymph nodes. It is found most often in women aged 30 or younger.

Age and exposure to the drug DES (diethylstilbestrol) before birth affect a woman's risk of developing vaginal cancer. Anything that increases your risk of getting a disease is called a risk factor. Risk factors for vaginal cancer include the following:

Being aged 60 or older. Being exposed to DES while in the mother's womb. In the 1950s, the drug DES was given to some pregnant women to prevent miscarriage (premature birth of a fetus that cannot survive). Women who were exposed to DES before birth have an increased risk of developing vaginal cancer. Some of these women develop a rare form of cancer called clear cell adenocarcinoma. Having human papilloma virus (HPV) infection. Having a history of abnormal cells in the cervix or cervical cancer.

Possible signs of vaginal cancer include pain or abnormal vaginal bleeding. Vaginal cancer often does not cause early symptoms and may be found during a routine Pap test. When symptoms occur they may be caused by vaginal cancer or by other conditions. A doctor should be consulted if any of the following problems occur:

Bleeding or discharge not related to menstrual periods.

Pain during sexual intercourse. Pain in the pelvic area. A lump in the vagina.

Tests that examine the vagina and other organs in the pelvis are used to detect (find) and diagnose vaginal cancer. The following tests and procedures may be used:

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken. Pelvic exam: An exam of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. The doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and places the other hand over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. A speculum is also inserted into the vagina and the doctor or nurse looks at the vagina and cervix for signs of disease. A Pap test or Pap smear of the cervix is usually done. The doctor or nurse also inserts a lubricated, gloved finger into the rectum to feel for lumps or abnormal areas.

Pelvic exam. A doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and presses on the lower abdomen with the other hand. This is done to feel the size, shape, and position of the uterus and ovaries. The vagina, cervix, fallopian tubes, and rectum are also checked. Pap smear: A procedure to collect cells from the surface of the cervix and vagina. A piece of cotton, a brush, or a small wooden stick is used to gently scrape cells from the cervix and vagina. The cells are viewed under a microscope to find out if they are abnormal. This procedure is also called a Pap test. Pap smear. A speculum is inserted into the vagina to widen it. Then, a brush is inserted into the vagina to collect cells from the cervix. The cells are checked under a microscope for signs of disease. Biopsy: The removal of cells or tissues from the vagina and cervix so they can be viewed under a microscope by a pathologist to check for signs of cancer. If a Pap smear shows abnormal cells in the vagina, a biopsy may be done during a colposcopy. Colposcopy: A procedure in which a colposcope (a lighted, magnifying instrument) is used to check the vagina and cervix for abnormal areas. Tissue samples may be taken using a curette (spoon-shaped instrument) and checked under a microscope for signs of disease. Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery) depends on the following:

The stage of the cancer (whether it is in the vagina only or has spread to other areas). The size of the tumor. The grade of tumor cells (how different they are from normal cells). Where the cancer is within the vagina. Whether there are symptoms. The patient's age and general health. Whether the cancer has just been diagnosed or has recurred (come back).

Treatment options depend on the following:

The stage, size, and location of the cancer. Whether the tumor cells are squamous cell or adenocarcinoma. Whether the patient has a uterus or has had a hysterectomy. Whether the patient has had past radiation treatment to the pelvis.

Vaginal Cancer

Author: Tarek Bardawil, MD, MBA; Chief Editor: Warner K Huh, MD

Updated: May 3, 2012 , MEDSCAPE

Overview
Malignant diseases of the vagina are either primary vaginal cancers or metastatic cancers from adjacent or distant organs. Primary vaginal cancers are defined as arising solely from the vagina, with no involvement of the external cervical os proximally or the vulva distally. The importance of this definition lies in the different clinical approaches to the treatment of upper and lower vaginal cancer. According to the International Federation of Gynecology and Obstetrics (FIGO), a vaginal lesion involving the external os of the cervix should be considered cervical cancer and treated as such; a tumor involving both the vulva and the vagina should be considered vulvar cancer. About 80% of vaginal cancers are metastatic, primarily from the cervix or endometrium. Metastatic cancer from the vulva, ovaries, choriocarcinoma, rectosigmoid, and bladder are less common. These cancers usually invade the vagina directly. Cancers from distant sites that metastasize to the vagina through the blood or lymphatic system also occur, including colon cancer, renal cell carcinoma, melanoma, and breast cancer. Although primary vaginal carcinoma is a rare gynecologic malignancy, its impact on women's health should not be underestimated, especially when considering the demographic increase in elderly women. As more women survive past age 60 years, physicians need to consider the likelihood that more women will present with vaginal cancer.

Because the 5-year survival rate of treated early stage vaginal cancer is significantly higher than that of vaginal cancer in the advanced stages, early detection is key to improving treatment outcomes. To improve outcomes of primary vaginal carcinoma, select referral oncology centers should see additional cases per month in order to plan appropriate randomized, prospective studies. This would increase the experience of any of these centers in treating primary vaginal carcinoma.
History of pelvic exenteration

In 1946, Alexander Brunschwig published the first cases of pelvic exenteration. In his first series, 5 of 22 surgical patients died from the operation itself. The original procedure consisted of connecting the ureters to the colostomy. In 1950, Bricker modified the procedure by isolating a loop of ileum, closing one end, anastomosing the ureters to it, and bringing the patent end out as a stoma.[1] Since then, several other modifications have improved the outcome of this procedure. Today, with vaginal reconstruction and continent vesicostomy, the procedure is accepted as a surgical treatment in selected cases.
Occurrence of vaginal cancer

Primary vaginal carcinoma is rare, constituting only 1-2% of all malignant gynecologic tumors. It ranks fifth in frequency behind cancer of the uterus, cervix, ovary, and vulva. The age-adjusted incidence in the United States is 0.6 per 100,000 population. The strict criteria used in defining vaginal carcinoma contribute to this low incidence.
HPV vaccine

In June 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the first vaccine developed to prevent cervical cancer and other diseases caused by HPV type 6, 11, 16, and 18. The vaccine is almost 100% effective in preventing precancerous lesions of the cervix, vulva and vagina, and genital warts caused by the HPV 6, 11, 16, and 18. The FDA has approved Gardasil for girls and women ages 9-26.
Patient education

For patient education information, see the Cancer Center and the Women's Health Center, as well as Vaginal Bleeding, Colposcopy, Cervical Cancer, and Bladder Control Problems.
Relevant Anatomy

The vagina is located in the true pelvis, which also contains the rest of the internal genital tract, the rectosigmoid, the bladder, the proximal urethra, and the pelvic portions of the ureters. The pelvic organs are partially covered by the peritoneum. The endopelvic fascia covers these organs and forms their supporting ligaments in conjunction with the pelvic vasculature and musculature. The pelvic cavity is divided into anterior and posterior compartments by the transversely positioned broad ligament. The uterus is centered within the broad ligament and is attached to the round ligaments, which run anterolaterally within the broad ligament from the uterus to the pelvic wall.

Anterior and posterior cul-de-sacs

The anterior cul-de-sac, also known as the vesicouterine pouch, is located between the uterus and the bladder. It has small, lateral recesses known as the paravesical fossae. This pouch ends where the cervix and the bladder connect and does not extend down to the vagina. The posterior cul-de-sac, known as the rectouterine pouch of Douglas, is located between the uterus (posteriorly) and the rectum (anteriorly). It is continuous with the pararectal fossae and contrary to the anterior pouch. It extends about 1-2cm down to the vagina, separating the cervix from the rectum.
Vaginal structure

The vagina itself is a muscular tube that extends from the cervix to the hymenal ring, penetrating the levator ani and the urogenital diaphragm. These latter structures provide vaginal support inferiorly. From the outermost to the innermost layers, the vagina is composed of an endopelvic fasciawhich contains an abundant plexus of vessels, lymphatics, and nervesas well as outer longitudinal and inner circular smooth muscle layers, submucosa, and mucosa.
Rectal and bladder pillars

The vagina is attached to the rectum posteriorly by the rectal pillars, while the bladder pillars provide anterior vaginal attachment to the bladder. During vaginal inspection with a speculum, the anterior and posterior sulci provide the anatomic landmark of the site of attachment of these pillars. These are most easily observed in nulliparous women. The rectal and bladder pillars are paired, parallel, longitudinal, fibrovascular bundles containing extensive vascular and lymphatic networks between the vagina and the rectum and bladder, respectively. They both run the entire length of the vagina. The bladder pillars also contain the paravaginal tissues (paracolpium). As it joins the lower end of the cervix, the upper end of the bladder pillar forms the vesicouterine ligament. This ligament forms a tunnel through which the ureters run inferomedially to reach the inferolateral portion of the bladder. The tunnel divides the vesicouterine ligament into anterior and posterior leaves. This anatomic structure is important during radical hysterectomy when careful dissection of the ligament is needed to mobilize the ureters. The rectal pillars receive the middle rectal arteries from the cardinal ligament.
Cardinal ligaments

The cardinal ligaments are wedge-shaped fibrovascular bundles containing the uterine, vaginal, inferior vesical, and middle rectal arteries and veins, as well as the lymphatic system. On each side, they run from the lateral aspect of the cervix to the lateral pelvic sidewall, traversing the pelvic plane at a 30 angle from the transverse pelvic diameter and dividing the paravesical and paravaginal spaces from the pararectal spaces. On the pelvic wall, they insert on the endopelvic fascia and the hypogastric vasculature. The anterior part of the cardinal ligament is more vascular, while the posterior part is more fibrous and contains the autonomic system of the bladder and rectum.

An important landmark is the uterine artery that crosses the anterior-most portion of the cardinal ligament. The ureter enters the upper portion of the ligament beneath this artery (water under the bridge) and 1-2cm lateral to the isthmus of the uterus. The uterine veins cross below the ureters.
Uterosacral ligaments

The uterosacral ligaments run from the posterolateral aspect of the cervix to the anterolateral part of the rectum. They are in close contact to the rectal pillars and straddle the posterior culde-sac.
Paravesical, pararectal, rectovaginal, and vesicovaginal spaces

Several avascular tissue planes are developed during pelvic surgery. The paravesical space is bordered by the symphysis pubis anteriorly, the cardinal ligaments posteriorly, the obliterated umbilical artery along the bladder medially, and the obturator internus laterally. The pararectal space is bordered by the cardinal ligament anteriorly, the sacrum posteriorly, the rectum medially, and the hypogastric artery laterally. The rectovaginal space is bounded by the vagina anteriorly and the rectum posteriorly, while the rectal pillars form its lateral walls. The vesicovaginal space is limited laterally by the bladder pillars, anteriorly by the bladder, and posteriorly by the vagina. To develop this space, the peritoneal reflection of the anterior cul-de-sac is entered.
Levator ani

The levator ani forms the major support of the pelvic structures and is the major component of the pelvic diaphragm. It is penetrated anteriorly by the rectum, vagina, and urethra. It forms the floor of all the planes discussed above.
Vaginal blood supply

The upper part of the vagina receives its blood supply from the uterine and the internal pudendal arteries, from which the vaginal artery arises. The inferior rectal artery and other branches arising from the internal pudendal artery supply the lower vagina. The vaginal venous plexus mainly drains into the pelvic wall through the parametrial veins, and to a lesser degree to the vesical and rectal plexuses.
Vaginal lymphatic system

Crossover of the vaginal lymphatic system is extensive. The middle to upper vagina communicates superiorly with the cervical lymphatics and drains into the pelvic obturator node, the internal and external iliac chains, and then the para-aortic nodes. The distal third of the vagina drains to the inguinal and then the pelvic nodes. The posterior wall lymphatics communicate with the rectal lymphatics and drain to the inferior gluteal, sacral, and rectal nodes.

Surgical considerations

The vagina stays in close proximity to the bladder and urethra anteriorly, which increases the risk of accidental injury to these structures during surgery. The sigmoid, on the other hand, reflects away from the posterior vaginal wall at its midpoint, facilitating an approach to the vagina posteriorly through the posterior cul-de-sac and a developed rectovaginal plane.

Risk Factors
The etiology of vaginal cancer has not been identified. Note that vaginal cancer is not histologically homogeneous; several types of lesions exist, each with its own characteristics, age predilection, aggressiveness, and prognosis (see Table 1, below). This suggests that a single etiologic factor is unlikely. Although some histologic types of vaginal cancer have been associated with exposure to certain agents, so far no clear cause-and-effect relationship has been found between any of those agents and vaginal carcinoma. Table 1. Most Common Forms of Primary Carcinoma of the Vagina (Open Table in a new window)
Cases of Vaginal Carcinoma Peak Age 60y

Histologic Type

Spread

Characteristics

Squamous cell carcinoma 85-87%

Local, blood, lymphatic Local

Most common in upper third of vagina

Verrucous carcinoma

Rare

60y

Variant of squamous cell, cauliflowerlike, aggressive, radiotherapy contraindicated Associated with in utero exposure to diethylstilbestrol (DES), tubulocystic pattern most favorable prognosis, late recurrence common White women, lower anterior vaginal wall, size more prognostically significant than invasion, poor prognosis Most common vaginal cancer among children, grapelike mass, strap cells

Clear cell adenocarcinoma 9%

19y

Local, blood, lymphatic

Melanoma

0.5-2%

60y

Local, blood, lymphatic

Sarcoma botryoides (embryonal rhabdomyosarcoma) Endodermal sinus tumor

Rare

3y

Local, blood, lymphatic

Very rare

10mo Local

Aggressive, alpha-fetoprotein (AFP) as

(yolk sac tumor) Leiomyosarcoma < 2% Wide Local, range blood, lymphatic

marker Grade is most important prognostic factor, can be secondary to pelvic irradiation

HPV and other infectious agents

The identification of HPV deoxyribonucleic acid (DNA) in squamous cell cancer cells by in situ hybridization (21%) and southern blot hybridization (56%) strongly suggests a possible role for HPV in the pathogenesis of squamous cell vaginal carcinoma.[2, 3] HPV subtypes 16 and 18 have the highest oncogenic potential and are most commonly linked to dysplastic changes in the female genital tract. Because HPV is sexually transmitted, this association raises the question as to whether women who engage in high-risk sexual behaviors, such as sex with multiple partners, are at risk for developing vaginal cancer. Another association that strengthens the link between HPV infection and vaginal cancer is the presence of a premalignant lesion in the vagina, known as vaginal intraepithelial neoplasia (VAIN). Aho and coworkers reported that 5-9% of patients treated for VAIN progressed to invasive carcinoma.[4] This suggested that VAIN may be a precursor to vaginal cancer even though the incidence of VAIN in the United States is 0.2-0.3 per 100,000 women[5] , which is less than the incidence of diagnosed vaginal cancer. This is because of the fact that women with VAIN are usually asymptomatic and that screening for VAIN is not recommended for the general population. Still, the true malignant potential of VAIN needs to be clarified. Other infectious agents that appear to be associated with vaginal cancer are herpes simplex virus (HSV) and Trichomonas vaginalis. In 2000, Lee and colleagues reported a case of rapidly progressive vaginal squamous cell carcinoma in a young woman with a 2-year history of human immunodeficiency virus (HIV) infection.[6] They suggested that young women infected with both HIV and HPV are at increased risk for a more aggressive and less responsive vaginal cancer.
History of carcinoma

A history of cervical intraepithelial neoplasia (CIN), invasive cervical carcinoma, or invasive vulvar carcinoma has also been associated with vaginal carcinoma. Several studies indicate that up to 30% of patients with primary vaginal carcinoma have a history of in situ or invasive carcinoma that was treated at least 5 years before diagnosis.
Diethylstilbestrol

Diethylstilbestrol (DES), a drug previously used in the first trimester to prevent pregnancy loss, has a strong association with clear cell adenocarcinoma of the vagina. Herbst and colleagues first observed this association in 1971,[7] which led to the discontinuation of DES that same year. By 1987, the Registry for Hormonal Transplacental Carcinogenesis, established by Herbst and Scully, identified 524 women with clear cell adenocarcinoma, but only 60% had a history

of DES exposure. Disease in the other 40% of patients with no history of DES exposure could be explained by recall bias or exposure to other unidentified factors. Women with in utero exposure to DES are at higher risk of developing adenocarcinoma than the general population. The estimated risk in these women is 1 in 1000.
Prior hysterectomy

Although 59% of women with vaginal cancer had a prior hysterectomy, in a 1986 report, Herman and colleagues demonstrated that when age and prior cervical cancer are controlled for, risk of vaginal cancer is not increased following hysterectomy for benign disease.[8] Note that hysterectomy by itself is not a risk factor; rather, women who underwent hysterectomy were poorly monitored.
Age

In a 2004 publication, Hellman et al reviewed 341 cases of primary carcinoma of the vagina from 1956-1996 and suggested that the etiology of vaginal cancer may be age related.[9] In younger women, the disease occurred in the upper part of the vagina and seemed to be related to cervical dysplasia and HPV infection, while in older patients, the tumors were exophytic. There was significant correlation with late menarche, suggesting hormonal factors and trauma to the vagina as probable etiologies.
Additional factors

Long-term pessary use and chronic irritation of vaginal mucosa in women with procidentia have been associated with vaginal cancer. Other predisposing factors include cigarette smoking, immunosuppressive therapy, chemotherapy, and radiation therapy. Approximately 10% of women diagnosed with primary vaginal carcinoma have a previous history of irradiation to the pelvis. Pukkala and colleagues reported an association between low socioeconomic class in Finland and an increased incidence of cervical, endometrial, and vaginal cancer.

Pathogenesis
The presence of different stages of histologic differentiation in vaginal cancerVAIN, carcinoma in situ, possible microinvasive carcinoma, and invasive cancersuggests a continuum of transformation from less malignant to more invasive; this is similar to the continuum described for cervical cancer.
HPV and history of carcinoma

On the other hand, the significant association of vaginal cancer with a history of cervical or vulvar cancer suggests that the entire genital tract is at risk for squamous cell carcinoma once malignancy has occurred anywhere along the tract; this is a phenomenon known as the "field effect."[11]

HPV infection, which evidence indicates is associated with the pathogenesis of squamous cell vaginal carcinoma, could explain this phenomenon, because HPV is associated with cervical, vaginal, and vulvar disease. Koyamatsu et al suggested that in cervical cancer, HPV 16 and 18 plays a common causal role, that in vulvar cancer, p53 gene mutations are the main carcinogenic cause, and that vaginal cancer has transitional characteristics between cervical and vulvar cancer. The investigators did a comparative analysis of the presence of HPV types 16 and 18 by polymerase chain reaction (PCR) assay and expression of p53 gene and Ki-67 antigen using immunohistochemistry in cervical, vaginal, and vulvar cancer.[12] There was no significant difference in overexpression of Ki-67 antigen among the 3 cancers. Another explanation for the association between vaginal cancer and cervical and vulvar carcinoma is that an occult residual disease such as VAIN is trapped within the vaginal cuff posthysterectomy and goes unnoticed until it develops into invasive carcinoma. This possibility illustrates the theory of the field effect and HPV infection, because HPV has also been linked to VAIN. It also partially explains why vaginal cancer in women who have undergone a hysterectomy goes unnoticed until the patients present with advanced-stage vaginal carcinoma. A third possibility for the association between vaginal cancer and carcinoma of the cervix or vulva is radiation carcinogenesis.
Diethylstilbestrol

The pathogenesis by which DES may play a role in inducing clear cell adenocarcinoma is unclear. In 1972, Forsberg and colleagues[13] proposed the possibility of estrogen-induced maturation arrest of the mllerian ducts, and in 1984, Robboy and colleagues[14] suggested that atypical vaginal adenosis and atypical cervical ectropion of the tuboendometrial type might act as the precursors of clear cell adenocarcinoma of the vagina and cervix.
Vaginal irritation

Most vaginal cancers occur in the upper third of the vagina. Reports are contradictory as to whether the anterolateral wall or the posterior wall is the more frequent site. Reports suggesting that the upper posterior wall is the most common site favor the hypothesis that irritating substances, such as vaginal secretions and semen, pool in the posterior fornix and cause chronic irritation, which could lead to induction of a carcinogenic process.

Metastasis
The proximity of the bladder anteriorly and the rectum posteriorly to the vagina predisposes these organs to direct invasion by the tumor. Lymphatic dissemination follows the lymphatic drainage of the vagina. The middle-to-upper vagina communicates superiorly with the lymphatics of the cervix and drains into the pelvic obturator node, the internal and external iliac chains, and then to the para-aortic nodes. The distal third of vagina drains to the inguinal node and then the pelvic node. Posterior wall lymphatics communicate with rectal lymphatics and drain to the inferior gluteal, sacral, and rectal nodes. Hematogenous dissemination to distant sites includes the lungs, liver, bone, and

skin. A submucosal lesion suggests that the malignancy is metastatic via the vaginal lymphatics.

Patient History
The duration of symptoms in vaginal cancer averages 6-12 months before diagnosis, with a range of 0-11 years. Delay in the diagnosis of vaginal carcinoma is not uncommon; this is partially due to the rarity of the disease, as well as with delays in relating patient symptoms to a vaginal origin. As expected, the longer the delay, the more advanced the cancer once the diagnosis is made, resulting in a poorer outcome. Painless vaginal bleeding is the most common symptom, accounting for 65-80% of all presentations. Bleeding is postmenopausal in about 70% of patients, which is consistent with the peak age of 60 years for squamous cell carcinoma, the most common type. Menorrhagia, intermenstrual bleeding, and postcoital bleeding have also been reported. Vaginal discharge occurs in 30% of patients, while 20% of patients report urinary symptoms, which are caused by an anterior lesion compressing or invading the bladder, the urethra, or both. This causes bladder pain, dysuria, urgency, and hematuria. About 15-30% of patients present with pelvic pain. Posterior lesions compress or invade the rectosigmoid, which causes tenesmus or constipation. Only 10% of patients report a vaginal mass or vaginal prolapse. In 2000, Eltabbakh and coworkers reported a single patient who presented with a cystic pelvic mass arising from the posterior vaginal wall that mimicked an ovarian neoplasm.[15] About 10-27% of patients are asymptomatic; diagnosis is made during routine pelvic examination. These patients tend to be caught at a much earlier stage than those presenting with symptoms, and their prognosis is much better.

Screening
Routine screening

Routine screening for vaginal carcinoma is not justified for all patients, because it is not cost effective. Women at risk, however, particularly those with a history of cervical neoplasia and risky sexual behavior, should receive a Papanicolaou test on a regular basis.
Screening after hysterectomy

Screening women with previous hysterectomy is controversial. In 1990, Manetta and colleagues suggested that women with previous hysterectomy should be counseled to continue their gynecologic cancer surveillance program.[16] They reported that 63% of patients who were diagnosed after the onset of their symptoms and who tended to have an unfavorable prognosis had undergone a prior hysterectomy. In a 1996 report, however, Pearce et al reviewed 9,610 vaginal smears from 5,682 women who underwent hysterectomy for benign gynecologic diseases and found that the probability

of an abnormal Papanicolaou smear in these women was 1.1%, with a 0% positive predictive value for detecting vaginal cancer.[17] Similarly, in 2000, Videlefsky et al[18] and Fetters et al concluded that routine vaginal cuff testing for most patients who underwent hysterectomy for benign conditions is not indicated. The American College of Obstetricians and Gynecologists recommends discontinuing screening in women who have undergone hysterectomy for benign diseases who have no prior history of high-grade cervical dysplasia. Women with a history of CIN 2 or CIN 3 are at increased risk of developing recurrent dysplasia or carcinoma of the vaginal cuff; therefore, in these women and in those in whom a negative history of high-grade dysplasia could not be verified, screening after hysterectomy should continue.[19]
Screening in women exposed to DES

Young girls who were exposed to DES in utero should be routinely examined starting at puberty or at the age of 14 years. Examination includes cytologic screening of the cervix and vagina, followed by careful inspection and palpation of the genital tract. Staining with halfstrength Lugol iodine helps to mark areas of adenosis. As long as cytologic findings are negative, colposcopy is unnecessary

Visual Examination, Palpation, and Biopsy

During routine vaginal examination, the speculum blades should be rotated laterally in order to visualize the anterior and posterior vaginal walls. Inspect all vaginal mucosa while withdrawing the speculum. Vaginal cancer is multifocal and, although it is typically located in the vaginal apex, the disease may involve any part of the vagina. Visual inspection alone is not enough, and careful circumferential palpation of the entire vagina is required in order to feel any raised or hardened areas. Vaginal lesions, particularly when small and located in the lower third of the vagina, are often missed during the first vaginal inspection because the blades of the speculum normally cover the anterior and posterior vaginal walls. This can lead to diagnostic delays. Frick and colleagues reported that about 19% of cases of vaginal cancer were missed on initial examination. Other reasons for delay are the rarity of vaginal carcinoma (1-2%) and the attribution of patient symptoms to more common diseases, such as postmenopausal bleeding and endometrial cancer. All visible lesions should be biopsied using either Eppendorf or Kevorkian punch biopsy forceps or similar instruments. Although the procedure is uncomfortable, local anesthesia is not recommended, because it is as uncomfortable as the biopsy itself. In elderly patients, particularly those with some degree of vaginal stenosis, the examination should be performed under general anesthesia to allow adequate biopsy.

Colposcopy
Patients with carcinoma in situ or very early invasive carcinoma are usually asymptomatic. Diagnosis is made when a routine Papanicolaou smear identifies abnormal cells. If the cervix

is present, then the physician must rule out cervical neoplasia, because cervical cancer is much more common than vaginal cancer. After a cervical origin has been ruled out through colposcopy, then the physician should perform a vaginal colposcopy. Because this is a time-consuming and difficult procedure, especially in elderly patients, it should be done under general anesthesia. Lugol iodine solution can help to identify regions to obtain biopsies from; malignant cells lack glycogen and so, unlike healthy vaginal mucosa, do not stain dark brown. Because healthy vaginal epithelium needs to be estrogenized in order to have sufficient glycogen, use of local estrogen cream for 1-2 weeks before examination may be helpful for postmenopausal patients. Estrogen cream should be discontinued 2 days prior to colposcopy. Patients with previous hysterectomy and abnormal cytologic findings should also undergo vaginal colposcopy. If no lesion is observed and the abnormal cytology persists, then resecting the vaginal cuff may be considered because the lesion may be buried in the closed vaginal cuff at the time of hysterectomy.

Histologic Findings
As mentioned before, primary vaginal carcinoma is not homogeneous. It is classified into several histologic types, each with its own characteristics (see Table 1). The following are brief descriptions of the most common types.
Squamous cell carcinoma

Squamous cell carcinoma is by far the most common type, accounting for 85-87% of all cases of primary vaginal carcinoma. It generally occurs in women older than 50 years and peak incidence is in people aged 60 years; however, several cases have been reported in women as young as 18 years. Grossly, it appears as an ulcerating lesion (50%), a fungating mass (30%), or an annular, constricting mass (20%). Secondary infections in an ulcerating tumor are common. Histologically, it resembles squamous cell carcinoma arising from the cervix, confusing the physician as to whether the lesion is cervical or vaginal in origin. This illustrates the need for a strict definition of primary vaginal carcinoma. The most common site of occurrence is the upper third of the vagina. Because of the thin vaginal wall, squamous cell carcinoma tends to spread early by directly invading the bladder and rectal walls. It also metastasizes through the blood or lymphatics. In 1981, Al-Kurdi and coworkers reported that about 28.6% of patients had pelvic lymph node involvement upon diagnosis.[20] Squamous cell carcinoma can metastasize to virtually any organ; cutaneous metastasis was reported by Plataniotis and colleagues.[21]
Verrucous carcinoma

Verrucous carcinoma is rare in the vagina and is more commonly observed in the vulva. It is observed in women older than 50 years and is considered a variant of squamous cell carcinoma. Its clinical and pathologic characteristics are similar to their vulvar counterparts.

On visual examination, verrucous carcinoma has a large, warty, cauliflowerlike appearance similar to that of condylomata acuminata, but the papillary fronds lack a central core of connective tissue. Verrucous carcinoma is slow growing, locally aggressive, and rarely metastatic. Radiation is contraindicated because it has been implicated in potentiating this tumor to a more malignant phenotype.
Clear cell adenocarcinoma

This is the second most common type of primary vaginal carcinoma, accounting for about 9% of all cases. Unlike squamous cell carcinoma, clear cell adenocarcinoma manifests in patients at a very early age, usually after age 14 years, with peak incidence in people aged 19 years. As discussed previously, an association with intrauterine exposure to DES has been established. The estimated risk in the exposed population is about 1 in 1000. Clear cell adenocarcinoma is thought to arise mainly from areas of vaginal adenosis but may also arise in wolffian rest elements, periurethral glands, and foci of endometriosis. In patients who have not been exposed to DES, ectopic cervical glands are a possible origin. Grossly, vaginal adenosis appears as multiple cysts 0.5-4cm in diameter or as a diffuse, erythematous, granular mucosal lesion. The cancerous lesion appears polypoid, papillary, flat, or ulcerated. Microscopically, 3 histologic patterns are predominant: tubulocystic, solid, and papillary. The tubulocystic pattern has the most favorable outcome. The tumor can spread by local invasion or by hematogenous or lymphatic dissemination. Upon presentation, 70% of cases are stage I disease, but recurrence is frequent and can occur as late as 20 years after initial therapy. Secondary tumors from the colon, endometrium, cervix, breast, or ovary should be considered.
Melanoma

Vaginal melanoma is rare, accounting for 0.5-2% of all primary vaginal cancers. Fewer than 150 cases have been reported. Vaginal melanoma tends to occur in white women; it usually manifests in women older than 50 years, with peak incidence in women aged 60 years. Melanoma is most commonly found in the lower anterior vaginal wall. Grossly, it appears as blue or black, soft, mucosal or submucosal nodules, but it may also be nonpigmented and is frequently ulcerated, mimicking squamous cell carcinoma. Histologically, it is similar to cutaneous melanoma, except that it is more invasive. Melanoma is thought to arise from melanocytes, which are present in 3% of healthy vaginas. The source probably is an aberrant melanocyte migration or melanocyte metaplasia. The Breslow and Clark systems are used as part of staging; however, because deep invasion is invariably present upon presentation, tumor size, rather than depth, is a more significant prognostic factor. Tumors tend to recur locally, and metastasis to the lungs is common.

Sarcoma botryoides (embryonal rhabdomyosarcoma)

Although this tumor is rare, it is the most common vaginal cancer in children. It manifests in girls younger than 8 years, with peak incidence in girls aged 3 years. Sarcoma botryoides is highly malignant and very aggressive. Initially, it tends to invade locally; it then metastasizes to the inguinal, pelvic, retroperitoneal, and mediastinal lymph nodes, as well as to the lungs, pericardium, liver, kidney, and bones. Grossly, sarcoma botryoides occurs in 2 structural forms: solid and multicystic grapelike. (The term botryoides comes from the Greek word botrys, which means grapes.) It originates in the subepithelial layers and expands outward to fill the vaginal cavity. Histologically, it is characterized by a loose, myxomatous stroma with malignant pleomorphic cells and characteristic cross-striated rhabdomyoblasts (strap cells), staining positively for muscle markers. Patients most commonly present with abnormal vaginal bleeding; they occasionally present with a polypoid mass protruding from the introitus.
Endodermal sinus tumor (yolk sac tumor)

This type of adenocarcinoma is very rare. It is classified as a germ cell tumor and most commonly occurs in the ovary. It manifests in patients at a very young age, usually girls younger than 2 years, and peak incidence is in babies aged 10 months. To date, about 20 vaginal cases have been documented. Characteristically, it secretes alpha-fetoprotein (AFP), which is frequently used as a marker of recurrence.
Vaginal leiomyosarcoma

This tumor of smooth muscle origin is rare and accounts for fewer than 2% of all primary vaginal cancers. It occurs over a wide patient age range, from 25 to 86 years, and may follow radiation therapy to the genital tract. Grossly, vaginal leiomyosarcoma manifests as a bulky submucosal lesion, mainly in the upper vagina. Histologically, it is similar to leiomyosarcoma of the uterus. Tavassoli and Norris established the following microscopic criteria to diagnose leiomyosarcoma of the vagina: moderate to marked atypia with 5 or more mitotic figures per 10 high-power fields (HPF). Histologic grade is the most important predictor of outcome

Treatment Determination and Staging

Once the diagnosis of cancer is established, staging should proceed to determine the best treatment. As with the other gynecologic cancers, staging is done according to FIGO classification. For vaginal cancer, staging is clinical and based on findings during general examination, pelvic examination, cystoscopy (for anterior wall tumors), proctoscopy (for posterior wall tumors), and chest radiography. If the patient reports bone pain, then skeletal radiography should be performed to rule out bone involvement.
Imaging

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the upper abdomen and pelvis are not FIGO recommendations, although they are frequently performed

because they help in establishing the presence of enlarged lymph nodes, ureteral compression, hydronephrosis, and liver metastasis. Oudouxa et al suggested that F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning provides a more accurate assessment of the extent of disease in a patient with malignant melanoma as compared with conventional methods.[23]
Antigen testing

Baseline levels of carcinoembryonic antigen (CEA), cancer antigen125 (CA-125), and squamous cell carcinoma antigen are recommended because they are elevated in patients with some carcinoma types.
Evaluation for origin and metastasis of adenocarcinoma

Patients in whom adenocarcinoma is diagnosed should undergo thorough exploration for possible metastasis, mainly in the uterus, cervix, ovary, and colon. In these patients, a fractional dilatation and curettage is indicated to rule out endometrial origin. A barium enema with either sigmoidoscopy or colonoscopy is also indicated to rule out colonic origin. In addition, mammography, chest radiography, and CT scanning of the abdomen or pelvis should follow. CA-125 should be taken as baseline for post-treatment follow-up.
Surgical staging

Surgical staging is not usually required, but it is performed in selected premenopausal patients prior to radiotherapy. In these patients, pretreatment laparotomy allows the transposition of at least 1 ovary away from the field of radiation. It also allows for better assessment of the extent of the disease through dissection of the pelvic lymph nodes. In addition, for patients scheduled for exenterative surgery, an exploratory laparotomy is required to rule out metastasis or lateral spread to the pelvic sidewall before proceeding with exenteration.
FIGO classification

FIGO staging classification of vaginal carcinoma is as follows:

Stage 0 - Carcinoma is carcinoma in situ (VAIN) Stage I - Carcinoma is limited to the vaginal wall Stage II - Carcinoma involves subvaginal tissue but has not extended to the pelvic wall Stage III - Carcinoma extends to the pelvic wall Stage IV - Carcinoma extends beyond the true pelvis or involves mucosa of bladder or rectum; bullous edema as such precludes inclusion in the stage IV classification Stage Iva - Carcinoma invades bladder or rectal mucosa or directly extends beyond the true pelvis Stage IVb - Carcinoma spreads to distant organs

Radiation Treatment and Chemotherapy

Primary vaginal cancer is so rare that large, randomized, controlled treatment trials are nearly impossible and, therefore, most treatment novelties are adopted from those for more common cancers, such as cervical and anal cancers.[24]

In 1999, the National Cancer Institute issued a clinical alert as to the importance of adding cisplatin-based chemotherapy concurrently with radiation in the treatment of locally advanced cervical cancer. This chemoradiation regimen led to significant improvement in progression-free and overall survival.[25] Since then, chemoradiation therapy has largely replaced radiation alone in the treatment of primary vaginal cancer. By analyzing data from 17 population-based cancer registries participating in the Surveillance, Epidemiology, and End Results (SEERS) program, Shirag et al noted a survival advantage in women treated for primary vaginal cancer that was temporally related to the advent of chemoradiation.

Indications and Contraindications for Surgery

Indications

Consensus as to the proper treatment for vaginal carcinoma is lacking, mainly because of the rarity of the disease. The most commonly used treatment modality is radiotherapy. Surgery, with or without concomitant radiation therapy, is indicated in the following conditions:

Squamous cell carcinoma - Stage I disease in the upper posterior vagina; stage IVa disease, particularly in the presence of a rectovaginal or vesicovaginal fistula; central recurrence after radiotherapy; ovary transposition in young patients prior to radiotherapy Clear cell adenocarcinoma - Although the etiology is different, the presentation may be similar to that of squamous cell carcinoma. Verrucous carcinoma - Radiation therapy is contraindicated because it has been implicated in potentiating this tumor to a more malignant phenotype; therefore, surgery is the only treatment Other cases - Melanoma, sarcoma, embryonal rhabdomyosarcoma, endodermal sinus tumor

Contraindications

Metastasis and extension to pelvic sidewalls are contraindications for exenteration. Microscopic pelvic node involvement is more of a controversy than a contraindication, and patients with positive pelvic nodes and no other poor prognostic factors can be considered candidates for exenteration. Involvement of both the pelvic and para-aortic nodes should warrant aborting the surgery.

Squamous Cell Carcinoma Surgery

Stage I disease

Stage I disease involving the upper posterior vagina is treated by radical hysterectomy, partial vaginectomy, and bilateral pelvic lymphadenectomy. Lymphadenectomy is required to ensure that metastatic disease is not present. If the patient had a previous hysterectomy, then a radical upper vaginectomy with pelvic lymphadenectomy is performed after the paravesicular and pararectal spaces are developed to avoid injury to the bladder and rectum, respectively. Each ureter is also dissected out to its point of entry into the bladder.

If the lesion is multifocal or if it extends to the lower third of the vagina, inguinal lymphadenectomy should also be performed, and a total vaginectomy is required. If the depth of the invasion is questioned during the operation, then a frozen section from the margins should be taken to ensure that tumor resection was adequate. In general, tumors of the upper posterior wall are more operable because the sigmoid reflects away from the posterior vaginal wall while the entire length of the anterior vaginal wall stays in close proximity to the bladder. A lower vaginal lesion can be treated with radical hemivulvectomy and lower vaginectomy with bilateral inguinal node dissection. Radiation therapy is commonly used as an alternative to surgery.
Stage II, III, and IV disease

Stages II and III are treated with radiation therapy. In premenopausal patients, a pretreatment laparotomy is performed in order to transpose the ovaries away from the field of radiation and to resect any enlarged lymph nodes. If the patient has a central recurrence with no signs of metastasis after radiotherapy, then pelvic exenteration is the only option. Patients with stage IVa disease have the option of radiation therapy or pelvic exenteration. The latter is highly recommended if a rectovaginal or vesicovaginal fistula is present. Stage IVb is a contraindication for surgery.

Clear Cell Adenocarcinoma Surgery

Therapeutic considerations are very similar to those for patients with squamous cell carcinoma, although most patients are young, and every effort should be made to preserve functional ovaries and a functional vagina. Surgery is the primary treatment modality. In stage I and early stage II disease, radical hysterectomy, pelvic lymphadenectomy, and vaginectomy with split-thickness skin graft have been successful. Alternatively, in 1987, Senekjian and colleagues reported a 5-year survival rate of 92% for patients with very early, small lesions treated by wide local excision, laparotomy for retroperitoneal lymphadenectomy, and local irradiation to the immediate adjacent tissues.[27] The best candidates are patients with tumors of less than 2cm in diameter, a predominant tubulocystic pattern, and a depth of invasion of less than 3cm. If radiation is used as the sole treatment, then transposition of at least 1 ovary up into the paracolic gutter beyond the radiation field should be done with pelvic lymph node dissection. Local excision without radiation is not recommended, since Herbst and colleagues reported that 16% of patients with stage I disease have positive pelvic nodes. Pelvic exenteration is done for central recurrences after primary irradiation. Matthews et al presented a case report on a fertility-sparing procedure, a radical abdominal trachelectomy and upper vaginectomy performed on a 22-year-old woman with clinical stage I vaginal clear cell adenocarcinoma in the left fornix. The authors found 28 months after the initial surgery that the woman had no evidence of recurrence and was having regular menstrual cycles. The authors concluded that this procedure can be considered to conserve fertility in young women.

Melanoma Surgery
The best treatment for vaginal melanoma remains controversial. Radical surgery has been the main treatment modality, although a more conservative approach has been advocated by some authors. For example, Reid et al, in 1989,[29] and Buchanan et al, in 1998,[30] , showed no significant difference in 5-year survival rates or disease-free intervals for radical versus conservative surgery. On the other hand, in 1994, Van Nostrand and colleagues demonstrated that radical surgery had a significant 2-year survival advantage over conservative surgery (48% vs 20%, respectively); they recommended a radical approach to patients with lesions smaller than 10cm2.[31]
Detection of lymph node involvement

Recently, detection of nodal involvement prior to radical procedures has been suggested because positive lymph nodes indicate poor prognosis and radical surgery might be unjustified. Siu et al used laparoscopic ultrasonography to successfully detect enlarged pelvic lymph nodes.[32] Rodier et al used technetium-99m (99m Tc)-sulfur colloid injected around the lesion and detected the sentinel lymph node with hot spot by lymphoscintigraphy.[33] Nakagawa et al succeeded in evaluating the sentinel lymph node to decide the extent of surgery using a dye injection method[34] ; 1mL of methylene blue was injected into the subcutaneous layer at the boundary between the lesion and the vaginal mucosa, followed by incision in the ipsilateral groin to detect the stained lymph node.
Radical surgery

Radical surgery varies depending on tumor size and location. Small lesions in the upper vagina are treated by radical hysterectomy, subtotal vaginectomy, and pelvic lymphadenectomy. Lesions in the lower vagina are managed by partial vaginectomy, total or partial vulvectomy, and bilateral inguinal lymphadenectomy. Larger and more invasive lesions (>3 mm) are treated with exenterative surgery. Note that whenever vaginal mucosa is left in situ after partial or subtotal vaginectomy, frozen sections should be obtained to exclude lateral superficial spread, because the most common site of initial recurrence is the vagina.
Conservative therapy

Conservative management includes wide local excision and simple hysterectomy combined with radiotherapy and/or chemotherapy. Radiation therapy with high-dose fractions (>400cGy/fx) has been effective in selected patients. This type of response is consistent with the higher response rate seen with cutaneous melanoma when large, individual fractions are compared with conventional fractionation.

Irvin et al reported in their case series higher locoregional control using wide local excision followed by high-dose fractionation teletherapy, compared with more radical surgical resection.[35]

Tumor Excision and Vaginal Resection in Other Cancers

Verrucous carcinoma

As mentioned previously, radiation therapy is contraindicated in verrucous carcinoma because it tends to induce aggressive cancer types. The only treatment option is surgical resection. If the lesion is small, a wide surgical excision is performed. With larger lesions, vaginectomy or exenteration is recommended. Because this tumor rarely metastasizes, dissecting the lymph nodes is unnecessary unless they appear enlarged.
Sarcoma botryoides

Because the typical patient is prepubertal, preserve ovarian function and reproductive organs. Currently, a conservative approach is used instead of exenterative surgery. Preoperative and/or postoperative chemotherapy and radiotherapy improve the outcome. For small, easily resectable tumors, the lesion is excised. Chemotherapy VAC (vincristine, actinomycin D, and cyclophosphamide) and radiotherapy follow. If the tumor is bulky, preoperative chemotherapy or radiotherapy is administered before the lesion is excised.
Endodermal sinus tumor

This very rare tumor is treated with chemotherapy VAC to reduce the tumor size. Chemotherapy is followed by partial colpectomy, radiotherapy, or both.
Vaginal leiomyosarcoma

These tumors vary in their malignancy depending on how well they are differentiated. Welldifferentiated tumors are less likely to metastasize and are managed by surgical excision. Frozen sections are taken to ensure that the tumor is well contained within the surgical margins. Poorly differentiated tumors should receive adjuvant radiotherapy.

Preoperative Evaluation for Exenterative Surgery

The first and most important requirement for exenterative surgery is that the patient have no underlying medical illnesses. The patient must be fit for a prolonged operation with potential blood loss and major fluid shifts. A psychological evaluation is also necessary; owing to postoperative physical and physiologic changes, the patient must have a stable personality and a supportive social environment. Signs of systemic spread should be absent. Evaluation starts with a physical examination, which includes palpation of all peripheral lymph nodes, especially the inguinal and supraclavicular nodes. The clinical triad of unilateral leg edema, sciatic pain, and ureteral obstruction suggest involvement of the posterolateral pelvic sidewall, which is a sign of lack of resectability. (Thus, extension of the tumor into the pelvic sidewall is a contraindication to

the procedure.) Each sign by itself is not a contraindication for exploratory laparotomy, although each is associated with decreased probability of resection and decreased probability of long-term survival, even if the cancer is resected with clear margins. Realize that age by itself is not a contraindication; the patient's health is the first prerequisite for considering pelvic exenteration.
Imaging

Chest radiography or CT scanning of the chest, upper abdomen, and pelvis are mandatory to rule out lung, liver, and para-aortic metastasis, respectively. Any suspicious lymph node should undergo fine-needle aspiration cytology to rule out metastasis. In a 1989 report, Manetta and colleagues dismissed the need to biopsy nonsuspicious supraclavicular lymph nodes in a random fashion. Unfortunately, neither CT scanning nor MRI is sensitive and specific enough to rule out pelvic sidewall involvement. This is because radiation fibrosis and chronic inflammation cannot be differentiated from cancer with these techniques.
Laparotomy and biopsy

If resectability is questionable, then an exploratory laparotomy with parametrial biopsies should be performed to rule out pelvic wall involvement. Alternatively, laparoscopy could be performed to obtain a biopsy from the pelvic wall and any suspicious lymph nodes. Miller and colleagues reported that nearly 30% of patients undergoing exploratory laparotomy had unresectable cancer because of peritoneal disease (44%), lymph node metastasis (40%), parametrial fixation (13%), and hepatic or bowel involvement (4.5%).[36]
Nutritional assessment and laboratory studies

Nutritional assessment is an important preoperative consideration because malnourished patients are at higher intraoperative and postoperative risk. Anthropometrics, serum electrolytes, total serum protein, albumin, transferrin, and immunologic function need to be evaluated. The latter is assessed by calculating the absolute lymphocyte count (reference range is >2000/mm3) and by examining delayed cutaneous hypersensitivity responses to skin test antigens.
Renal evaluation

Kidney function must be evaluated because the patient is at risk for massive fluid shifts and major blood loss and because urinary diversion is likely to be performed. A complete urine analysis with serum creatinine provides a good evaluation.
Hematologic evaluation

A complete blood count (CBC) is required, and hemostatic function is evaluated through patient history of bleeding and family history of coagulopathy. Also, prothrombin time (PT) and activated partial thromboplastin time (aPTT) are required because cancer is associated with coagulation abnormalities.

Cardiac evaluation

Consult an electrocardiography (ECG) specialist and cardiologist. Clear the patient from cardiac risks before surgery because most patients are older than 50 years and may have underlying coronary heart disease. Also, the surgery is radical in nature, with unavoidable blood and fluid losses.

Patient Counseling in Exenterative Surgery

Once the patient is medically cleared for surgery, she should undergo extensive preoperative counseling. During counseling, the patient should be informed that preoperative evaluation of tumor resectability is not as accurate as intraoperative assessment; therefore, the possibility of aborting the procedure still exists. The patient should also be informed of the radical nature of the surgery and of all possible intraoperative and postoperative complications, including intraoperative mortality. She should be informed that intraoperative and postoperative blood product administration is inevitable and that a postoperative stay in the intensive care unit (ICU) and prolonged hospitalization are common. The patient should also expect an alteration in her physical appearance and physiologic function, such as the presence of stomas, and should understand the possible psychological impact such alteration will have on her. The patient should be offered vaginal reconstruction and be given the option, if it exists, to choose the donor sites for skin grafts and musculocutaneous flaps.[37] Most importantly, the patient should know that despite the radical nature of the surgery, cure is not guaranteed.

Radical Hysterectomy
The objective of a radical hysterectomy is resection of the tissue adjacent to the cervix and vaginal fornices, along with removal of the uterus and cervix and the part of the vagina involved by the lesion, while preserving a functional urinary apparatus and rectum. The procedure starts with a midline incision as previously described for exenteration. Alternatively, a low transverse Maylard or Cherney incision provides adequate exposure to the pelvis but not enough to explore the entire abdomen. For this reason, a midline incision is preferable. Abdominal exploration is performed as previously described. Steady upward traction is applied to the uterus, and the retroperitoneum is entered through the round ligaments on both sides. Once the ureter is identified as it crosses the pelvic rim, the pelvic spaces are developed as before. The vesicouterine fold of the peritoneum is opened, and the bladder is dissected away from the cervix and upper vagina. If the bladder is involved, then an anterior exenteration is performed. The uterine artery is ligated at its origin from the superior vesicle or internal iliac artery and then mobilized over the ureter. The uterine veins are clipped to avoid excessive bleeding.

The anterior vesicouterine ligament, which forms the roof of the uteric tunnel, is carefully dissected. This allows mobilization of the ureters off their peritoneal attachments and away from the uterus. Care must be taken to avoid severing the blood supply to the ureters. Once this is done, the posterior vesicouterine ligament could be divided. This frees the uterus from its anterior attachments in the pelvis. Posteriorly, the peritoneum over the Douglas pouch is incised and the rectovaginal space developed by applying smooth traction on the rectum. This allows dissection and division of the uterosacral ligaments midway from the sacrum, which frees the uterus from its posterior attachment in the pelvis. To release the uterus from its lateral pelvic attachment, the cardinal ligaments are clamped and divided at the level of the pelvic sidewall, all the way across the paravaginal tissues down to the vagina. If the ovaries are to be preserved, then the ovarian ligaments and fallopian tubes are transected. Otherwise, the infundibulopelvic ligaments are divided and the ovaries are freed from the pelvic attachments and removed with the uterus. A vaginectomy is performed by continuing the dissection of the vesicovaginal and rectovaginal spaces and dividing the bladder and rectal pillars down to the pelvic floor. The vagina is entered anteriorly and transected at the desired level using a knife or scissors. The vault is closed, and the vaginal angles are sutured to the paravaginal tissues. The pelvic peritoneum is not closed, and drains are used only if doubt exists regarding the adequacy of hemostasis. In 1993, Jensen and colleagues reported that drains may increase febrile morbidity, pelvic cellulitis, and postoperative ileus.[44] A suprapubic catheter is placed in the bladder.

Vaginectomy
Radical vaginectomy is employed for invasive vaginal carcinoma, while simple vaginectomy is performed in cases of VAIN. Vaginectomy may be partial, subtotal, or total, depending on the extent of the disease, how well-circumscribed the lesion is, and whether it is multifocal. The excision should include 2cm of normal vagina distal to the lesion and the entire vagina proximal to the lesion. If more than a third of the upper vagina is removed, then vaginal reconstruction using a splitthickness skin graft is required in order to have normal sexual function.
Simple vaginectomy

Simple vaginectomy is indicated when invasion is suspected in a patient with VAIN. The approach usually is vaginal. In postmenopausal women with poorly estrogenized vaginal mucosa, estrogen cream can be used 2-4 weeks prior to the operation. Lugol solution is used to delineate the abnormal mucosa. Injecting saline solution into the submucosa elevates the lesion from the underlying tissue layer and helps in the excision. Usually, a 3-5mm margin of healthy mucosa is adequate. For lesions located in the upper vagina, sutures are placed in the apex to place traction and the upper vagina is excised. The bladder and rectal pillars (lymph vascular pillars) are transected from their vaginal attachments. Blunt dissection is used to further remove the specimen. The surgeon must keep in mind the proximity of the ureters to the corners of the apex. The vagina is closed with interrupted biodegradable sutures.

Radical vaginectomy

When the uterus is in situ, radical vaginectomy can be approached vaginally or abdominally. If two thirds of the vagina needs to be removed, however, a combined approach is required to mobilize the distant vagina. In patients with previous hysterectomy, the abdominal approach or a combined approach is required because of a higher risk of injury to the ureters during resection of the cardinal ligaments and the proximal bladder pillars. The vesicovaginal (anterior), rectovaginal (posterior), and 2 lateral paravaginal spaces are developed, and the bladder and rectal pillars are transected at their attachments to the bladder and rectum, respectively (as opposed to their vaginal attachments in simple vaginectomy). The ureters should be dissected away before resection of the vagina with the cardinal and vesicouterine ligaments. The specimen is resected in a manner similar to that used in simple vaginectomy.

Postoperative Details
The NG tube is removed in the recovery room or at the end of the surgery. Upon admission to the recovery room, chest radiography is performed to rule out pneumothorax and to check the tip of the central line. When stabilized, the patient is transferred to the ICU. Fluid status is accurately measured by Swan-Ganz catheter because urine output may not be reliable (because of the diversion) and large loss of fluid is expected because of third spacing and oozing of serum from the large abdominal and pelvic defects. The urostomy is placed on continuous gravity drainage. Hemovac drainage should be measured and used as an indication for proper replacement of protein and electrolyte losses because drainage content is an approximation of serum content. The volume of the pelvic drainage can reach up to 1000mL over 24 hours. An arterial line should be available for blood product, colloid, and crystalloid administration; fluid replacement should be adequate to avoid intravascular compromise with renal hypoperfusion and failure. The hematocrit should be carefully monitored and stabilized above 30% by infusing packed red blood cells (RBCs) or whole blood when needed. PT and aPTT are kept within the reference range with administration of fresh frozen plasma (FFP). Routinely check the lower extremities for evidence of adequate vascular perfusion, with daily checks for evidence of DVT. Continuously monitor the patient's respiratory and cardiac function for evidence of pulmonary embolus, atelectasis, pleural effusion, and cardiac ischemia. When the patient is stabilized, the Swan-Ganz catheter is J-wired and a central line is placed for total parenteral nutrition (TPN), usually on postoperative day 2 or 3. Antibiotic prophylaxis is discontinued after 48 hours if no postoperative fever has been reported. Otherwise, the antibiotic is changed according to the fever workup and cultures are obtained. If the cultures are negative for infection, then the antibiotics should be changed to cover anaerobic and gram-negative organisms. Check stomas daily for evidence of vascular perfusion. If a stoma becomes dusky, then a scope is introduced to check the condition of the underlying bowel. Once bowel sounds are auscultated and the patient passes flatus, then oral feeding is initiated; the TPN is withdrawn when oral intake is adequate.

Intermittent, pneumatic calf compression is continued until the patient is fully ambulatory. Ambulation should begin as soon as the patient's strength is regained and pain is well controlled.

Postoperative Follow-Up
Regarding outcome and prognosis, the main concern of the patient and physician is the possibility of recurrence of the primary disease. After surgery, monitor the patient for complications and any sign of recurrence. No data exist regarding the frequency and effectiveness of follow-up care for recurrence. In general, patients receive a pelvic examination and Papanicolaou smear every 3-6 months for the first 5 years. Patients treated for clear cell adenocarcinoma need to be monitored for a long time because late recurrences and second primaries in DES-exposed women have been reported to occur 17-20 years after the initial treatment, particularly in the lungs and supraclavicular areas. As many as 36% of recurrences appear in extrapelvic sites. Follow-up for postoperative complications includes evaluation of the stomas, observation of the incisions for healing, and evaluation for signs of necrosis in split-thickness skin grafts and musculocutaneous flaps. Psychological evaluation includes questions about quality of life, body image, and sexual satisfaction. Patients should be counseled about these issues.

Complications
Exenteration

The overall mortality rate for patients undergoing exenteration is less than 5%; however, complications occur in about 50% of patients, because of the nature and length of surgery, the advanced age of the patients, the large amount of blood loss, and the inability to accurately monitor fluid intake and output secondary to urinary diversion. Hemorrhage is the most significant intraoperative complication (1.5-4L).
Postoperative complications

Hemorrhage should be dealt with promptly with percutaneous embolization because reexploration carries high mortality and morbidity rates. Intravascular fluid loss from wound oozing and third spacing is expected. Pelvic sepsis (10%) and wound sepsis and dehiscence (12%) are minimized by bowel preparation, but the risk is still present because of the radical nature of the surgery, the length of the operation, and the age of the patient. Pulmonary embolus occurs in 1.5% of patients despite prophylaxis. This is also due to the length of the operation and prolonged bed rest after surgery.

Lower rectal anastomosis complications

Anastomotic leakage depends on the distance of the anastomosis from the anus, as well as on the vascularity and tension on the anastomotic site. Along with fistulae, it carries a very high mortality rate of approximately 50%. Rectovaginal fistulae and strictures are more common in patients with previous irradiation. Using the omentum as an additional blood supply could prevent this. The inability to empty the J-pouch is the most significant drawback to this procedure. Small bowel obstruction occurs in 4-9% of patients. The most common site is the distal ileum if an ileal anastomosis has been performed, with obstruction most frequently occurring if irradiation was previously administered. Avoiding an ileal anastomosis and generously reconstructing the pelvic floor decreases this complication. In case of an obstruction, reoperation should not be considered, because of its high mortality rate (8-10%). Instead, NG decompression should be attempted and TPN feeding continued. Fistulae (12-32%) are more common with ileoileal anastomosis and previous irradiation. With the use of a transverse colon conduit for urinary diversion, this complication now is uncommon. With the use of a transverse colon, urinary leaks and intestinal fistulae now are rare. In case they occur, management is conservative because of the high mortality rate associated with reoperation. Percutaneous drainage is required. Ureteral strictures are uncommon with the use of stents. The long-term complication is pyelonephritis, with 2.7% risk of renal failure due to ureteral obstruction.[45]
Vaginal reconstruction

Complications from vaginal reconstruction include necrosis of the graft and stenosis of the neovagina.
Other complications

TPN complications include pneumothorax (1-2%), which is diagnosed on the basis of chest radiographic findings. It usually resolves spontaneously, but a chest tube may be required. Subclavian venous thrombosis occurs in 5-10% of patients. Flush with heparin solution (300U/mL) for prevention. Once it occurs, remove the catheter, administer a full course of heparin, and continue nutrition through a peripheral vein. Infection occurs in 2-5% of patients. If the patient is febrile and the source of infection is not identified after 96 hours, remove the catheter and send the catheter tip for culture. If a peripheral source was identified, then removing the catheter is unnecessary; treat the infection accordingly. Metabolic complications include overfeeding (most common; leads to excess carbon dioxide production), hyperglycemia (treat with insulin), and metabolic acidosis (rare with addition of acetate buffer).

Postoperative Prognosis Following Exenteration

The outcome of exenteration has improved significantly over time in terms of operative mortality and 5-year survival rates. In 1965, Brunschwig reported an operative mortality rate of 16% and a 5-year survival rate of 20%[46] ; in 1989, Morley et al reported an operative mortality rate of 2% and a 5-year survival rate of 61%[47] . In general, the operative mortality rate in exenteration is less than 5%, and the 5-year survival rate is about 40%. Improved hemodynamic monitoring, nutritional support, and advances in surgical techniques and instruments have contributed to the decrease in intraoperative mortality and morbidity. Anterior exenteration has a better survival rate than does total exenteration (30-60% versus 20-46%, respectively). In a study of outcomes from pelvic exenteration, Maggioni et al found that the 5-year survival rate was highest for patients with cervical cancer (52%) but was only 19% for vaginal cancer. The authors published their 10-year experience with pelvic exenteration between June 1996 and April 2007 for cancers of the cervix (62 patients), vagina (21 patients), vulva (9 patients), endometrium (9 patients), and ovary (4 patients) and for uterine sarcoma (1 patient). In the study, the survival of patients with cervical and vaginal cancer was significantly affected by the presence of positive lymph node involvement (30% vs 60% at 5 years) and positive margins (25% vs 60% at 5 years). There was no operative or early postoperative mortality (< 30 days after surgery), but the postoperative complication rate was 66.6%, with 87% of early complications being completely resolved.[48]
Clinical factors that affect survival

These include the following:

Length of time from initial radiation therapy to exenteration - Less than 1 year is a poor prognostic sign. Size of the central mass (>3 cm) Preoperative sidewall fixation as determined by clinical examination

Pathologic factors that affect survival

Pathologic factors that impact survival include the following:

Tumor extension - In 1989, Anthopoulos and colleagues reported that the most important risk factor for reduced survival was the extension of the tumor laterally into the surgical margins[49] Positive nodes - In 1989, Morley et al reported a 5-year survival rate of 70% for negative nodes versus 0% for positive nodes[47] Spread of tumor to adjacent organs

Additional factors in prognosis

Age can affect the operative mortality rate but not the 5-year survival rate. In 1992, Matthews et al reported that patients older than 65 years had the same 5-year survival rate of 45% as

patients younger than 65 years.[50] The operative mortality rate of the older group was 11% versus 8.5% in the younger group. Anthopoulos et al found that 84% of the patients were rehospitalized for complications that occurred more than 30 days after surgery; complications usually involved the gastrointestinal or urinary tract.[49] Surgical intervention was required for 58% of patients with complications occurring 1 year after surgery, while 74% required surgery within the first year. Organ reconstruction, including low rectal anastomosis, continent vesicostomy, and vaginal reconstruction, has significantly improved patients quality of life after pelvic exenteration. In 1997, Hawighorst-Knapstein and colleagues reported that patients with no ostomies have a much better quality of life and body image than patients with 2 ostomies.[51] They also reported that women with vaginal reconstruction reported fewer problems related to quality of life and significantly fewer sexual problems

Cervical Cancer

Author: Cecelia H Boardman, MD; Chief Editor: Warner K Huh,

Updated: Feb 20, 2013

Practice Essentials
Cervical cancer is the third most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries. In the United States, cervical cancer is relatively uncommon. Essential update: Bevacizumab extends survival in advanced cervical cancer In a study of 452 patients with pretreated metastatic, recurrent, or persistent cervical cancer that was not curable with standard surgery and/or radiotherapy, bevacizumab significantly extended survival by almost 4 months. Median survival among women treated with chemotherapy plus bevacizumab was 17.0 months, compared with 13.3 months among those treated with chemotherapy alone. Bevacizumab was administered intravenously at a dose of 15 mg/kg of body weight for 1 day every 3 weeks until the occurrence of disease progression or unacceptable toxicity.[1]
Signs and symptoms

The most common finding in patients with cervical cancer is an abnormal Papanicolaou (Pap) test result. Physical symptoms of cervical cancer may include the following:

Abnormal vaginal bleeding Vaginal discomfort Malodorous discharge Dysuria

See Clinical Presentation for more detail.

Diagnosis

Human papillomavirus (HPV) infection must be present for cervical cancer to occur. Complete evaluation starts with Papanicolaou (Pap) testing. Screening recommendations Current screening recommendations for specific age groups, based on guidelines from the American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP), the American Society for Clinical Pathology (ASCP), the US Preventive Services Task Force (USPSTF), and the American College of Obstetricians and Gynecologists (ACOG), are as follows[2, 3, 4, 5] :

< 21 years: No screening recommended 21-29 years: Cytology (Pap smear) alone every 3 years 30-65 years: Human papillomavirus (HPV) and cytology cotesting every 5 years (preferred) or cytology alone every 3 years (acceptable) >65 years: No screening recommended if adequate prior screening has been negative and high risk is not present

See Workup for more detail.

Management

Immunization Evidence suggests that HPV vaccines prevent HPV infection.[6] The following 2 HPV vaccines are approved by the FDA:

Gardasil (Merck, Whitehouse Station, NJ): This quadrivalent vaccine is approved for girls and women 9-26 years of age to prevent cervical cancer (and also genital warts and anal cancer) caused by HPV types 6, 11, 16, and 18; it is also approved for males 9-26 years of age[7] Cervarix (GlaxoSmithKline, Research Triangle Park, NC): This bivalent vaccine is approved for girls and women 9-25 years of age to prevent cervical cancer caused by HPV types 16 and 18[8]

The Advisory Committee on Immunization Practices (ACIP) recommendations for vaccination are as follows:

Routine vaccination of females aged 11-12 years of age with 3 doses of either HPV2 or HPV4 Routine vaccination with HPV4 for boys aged 11-12 years of age, as well as males aged 13-21 years of age who have not been vaccinated previously Vaccination with HPV4 in males aged 9-26 years of age for prevention of genital warts; routine use not recommended

Stage-based treatment The treatment of cervical cancer varies with the stage of the disease, as follows:

Stage 0: Carcinoma in situ (stage 0) is treated with local ablative or excisional measures such as cryosurgery, laser ablation, and loop excision; surgical removal is preferred Stage IA1: The treatment of choice for stage IA1 disease is surgery; total hysterectomy, radical hysterectomy, and conization are accepted procedures Stage IA2, IB, or IIA: Combined external beam radiation with brachytherapy and radical hysterectomy with bilateral pelvic lymphadenectomy for patients with stage IB or IIA disease; radical vaginal trachelectomy with pelvic lymph node dissection is appropriate for fertility preservation in women with stage IA2 disease and those with stage IB1 disease whose lesions are 2 cm or smaller Stage IIB, III, or IVA: Cisplatin-based chemotherapy with radiation is the standard of care[9] Stage IVB and recurrent cancer: Individualized therapy is used on a palliative basis; radiation therapy is used alone for control of bleeding and pain; systemic chemotherapy is used for disseminated disease[9]

See Treatment and Medication for more detail.

Image library

Cervical carcinoma with adnexa.

Background
Cervical cancer is the third most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries. In the United States, cervical cancer is relatively uncommon. (See Epidemiology.) The incidence of invasive cervical cancer has declined steadily in the United States over the past few decades; however, it remains at high levels in many developing countries. The change in the epidemiologic trend in the United States has been attributed to mass screening with Papanicolaou (Pap) tests, which permits detection and treatment of preinvasive disease. Recognition of the etiologic role of human papillomavirus (HPV) infection in cervical cancer has led to the recommendation of adding HPV testing to the screening regimen in women 3065 years of age (see Workup). However, women who have symptoms, abnormal screening test results, or a gross lesion of the cervix are best evaluated with colposcopy and biopsy. For further recommendations concerning cervical cancer evaluation and management of abnormal Pap test results, and treatment of cervical intraepithelial neoplasia (CIN), see the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines.[10] (See also Presentation and Workup.) The treatment of cervical cancer varies with the stage of the disease. For early invasive cancer, surgery is the treatment of choice. In more advanced cases, radiation combined with chemotherapy is the current standard of care. In patients with disseminated disease, chemotherapy or radiation provides symptom palliation. (See Treatment and Medication.)

Pathophysiology
Human papillomavirus (HPV) infection must be present for cervical cancer to occur. HPV infection occurs in a high percentage of sexually active women. However, approximately 90% of HPV infections clear on their own within months to a few years and with no sequelae, although cytology reports in the 2 years following infection may show a low-grade squamous intraepithelial lesion. On average, only 5% of HPV infections will result in the development of CIN grade 2 or 3 lesions (the recognized cervical cancer precursor) within 3 years of infection. Only 20% of CIN 3 lesions progress to invasive cervical cancer within 5 years, and only 40% of CIN 3 lesions progress to invasive cervical cancer with 30 years. Because only a small proportion of HPV infections progress to cancer, other factors must be involved in the process of carcinogenesis. The following factors have been postulated to influence the development of CIN 3 lesions:

The type and duration of viral infection, with high-risk HPV type and persistent infection predicting a higher risk for progression; low-risk HPV types do not cause cervical cancer Host conditions that compromise immunity (eg, poor nutritional status, immunocompromise, and HIV infection) Environmental factors (eg, smoking and vitamin deficiencies) Lack of access to routine cytology screening

In addition, various gynecologic factors significantly increase the risk of HPV infection. These include early age of first intercourse and higher number of sexual partners. Although use of oral contraceptives for 5 years or longer has been associated with an increased risk of cervical cancer, the increased risk may reflect a higher risk for HPV infection among sexually active women. However, a possible direct interaction between oral contraceptives and HPV infection has not been disproved.[11]
Genetic susceptibility

Genetic susceptibility to cervical cancers caused by HPV infection has been identified via studies of twins and other first-degree relatives, as well as genome-wide association studies. Women who have an affected first-degree biologic relative have a 2-fold relative risk of developing a cervical tumor compared with women who have a nonbiologic first-degree relative with a cervical tumor.[12, 13] Genetic susceptibility accounts for fewer than 1% of cervical cancers. Genetic changes in several classes of genes have been linked to cervical cancer. Tumor necrosis factor (TNF) is involved in initiating the cell commitment to apoptosis, and the genes TNFa-8, TNFa-572, TNFa-857, TNFa-863, and TNF G-308A have been associated with a higher incidence of cervical cancer.[14, 15, 16, 17] Polymorphisms in another gene involved in apoptosis and gene repair, Tp53, have been associated with an increased rate of HPV infection progressing to cervical cancer.[18, 19, 20, 21, 22] Human leukocyte antigen (HLA) genes are involved in various ways. Some HLA gene anomalies are associated with an increased risk of HPV infection progressing to cancer,[23, 24]

others with a protective effect.[25, 26] The chemokine receptor-2 (CCR2) gene on chromosome 3p21[27, 28] and the Fas gene on chromosome 10q24.1[24, 29] may also influence genetic susceptibility to cervical cancer, perhaps by disrupting the immune response to HPV. The CASP8 gene (also known as FLICE or MCH5) has a polymorphism in the promoter region that has been associated with a decreased risk of cervical cancer.[30] Epigenetic modifications may also be involved in cervical cancer. Methylation is the best understood and probably the most common mechanism of epigenetic DNA modeling in cancer. Aberrant DNA methylation patterns have been associated with the development of cervical cancer and may harbor important clues for developing treatment.[31, 32]
Human papillomavirus

HPV comprises a heterogeneous group of viruses that contain closed circular double-stranded DNA. The viral genome encodes 6 early open reading frame proteins (ie, E1, E2, E3, E4, E6, and E7), which function as regulatory proteins, and 2 late open reading frame proteins (ie, L1 and L2), which make up the viral capsid. To date, more than 115 different genotypes of HPV have been identified and cloned. A large multinational cervical cancer study found that more than 90% of all cervical cancers worldwide are caused by 8 HPV types: 16, 18, 31, 33, 35, 45, 52, and 58. Three types16, 18, and 45cause 94% of cervical adenocarcinomas.[33] HVP type 16 may pose a risk of cancer that is an order of magnitude higher than that posed by other high-risk HPV types.[34] The World Health Organization (WHO) International Agency for Research on Cancer Monograph Working Group has grouped HPV types of the mucosotropic alpha genus according to the evidence supporting their association with cervical cancer (see Table 1, below).[34] Table 1. Human Papillomavirus Types Associated With Cervical Cancer (Open Table in a new window)
HPV Alpha Group 1 16 Types Evidence for Cervical Cancer Causation Most carcinogenic HPV type, known to cause cancer at several sites

18,31,33,35,39,45,51,52,56,58, Sufficient evidence 59 2A 68 Limited evidence in humans and strong mechanistic evidence Limited evidence in humans Classified by phylogenetic analogy to HPV types with sufficient or limited evidence in humans

2B

26,53,66,67,70,73,82 30,34,69,85,97

6,11

Inadequate epidemiological evidence and absence of carcinogenic potential in mechanistic studies

HPV = human papillomavirus.

The HPVs that infect the human cervix fall into 2 broad risk categories. The low-risk types (eg, HPV 6 and 11) are associated with condylomata and a very small number of low-grade squamous epithelial lesions (SILs) but are never found in invasive cancer. The high-risk types (eg, HPV 16) vary in prevalence according to the cervical disease state. Upon integration into the human genome, the linearization of high-risk HPV DNA places the E6 and E7 genes in a position of enhanced replication. E7 binds and inactivates the Rb protein while E6 binds p53 and directs its degradation, and the functional loss of the TP53 and RB genes leads to resistance to apoptosis, causing uncensored cell growth after DNA damage. This ultimately results in progression to malignancy.
Human immunodeficiency virus

The role of HIV infection in the pathogenesis of cervical cancer is not fully understood. However, HIV infection is known to suppress the already low level of immune recognition of HPV infection, allowing HPV to cause more damage than it would in immunocompetent women. Cervical cancer is at least 5 times more common in HIV-infected women, and this increased prevalence has remained essentially unchanged with the use of highly active antiretroviral therapy.[35] Studies have shown a higher prevalence of HPV infection in HIV-seropositive women than in seronegative women, and the HPV prevalence was directly proportional to the severity of immunosuppression as measured by CD4+ T-cell counts.

Etiology
With rare exceptions, cervical cancer results from genital infection with HPV, which is a known human carcinogen.[36, 37, 38, 34, 39] Although HPV infections can be transmitted via nonsexual routes, the majority result from sexual contact. Consequently, major risk factors identified in epidemiologic studies are as follows:

Sex at a young age Multiple sexual partners Promiscuous male partners History of sexually transmitted diseases

HIV infection is associated with a 5-fold increase in the risk of cervical cancer, presumably because of an impaired immune response to HPV infection.[35] Exposure to diethylstilbestrol in utero has been associated with an increased risk of CIN grade 2 or higher.[40]

Epidemiology
Cervical cancer is the third most common malignancy in women worldwide. The frequency varies considerably between developed and developing countries, however: Cervical cancer is the second most common cancer in developing countries, but only the tenth most common in developed countries. Similarly, cervical cancer is the second most common cause of cancer-related deaths in women in developing countries but is not even among the top 10 causes in developed countries.[41] In the United States, cervical cancer is relatively uncommon. The incidence of invasive cervical cancer has declined steadily in the US over the past few decades; for example, since 2004, rates have decreased by 2.1% per year in women younger than 50 years and by 3.1% per year in women 50 years of age and older.[42] This trend has been attributed to mass screening with Pap tests.[43] Cervical cancer rates continue to rise in many developing countries, however. The American Cancer Society (ACS) estimates that in the United States, 12,170 new cases of cervical cancer will be diagnosed in 2012.[42] Internationally, more than 500,000 new cases are diagnosed each year; rates vary widely, ranging from an annual incidence of 4.5 cases per 100,000 in Western Asia to 34.5 per 100,000 women in Eastern Africa.[44] In industrialized countries with well-established cytology screening programs, the incidence of cervical cancer ranges from 4 to 10 per 100,000 women. The incidence of CIN 2/3 disease in the US is about 150 per 100,000 women, with the peak incidence around 800 per 100,000 women in the 25-29 year age group. The incidence of abnormal cytology screens for all ages is an order of magnitude larger, at 7800 per 100,000 women. Forouzanfar et al performed annual age-specific assessments of cervical cancer in 187 countries from 1980 to 2010. The global cervical cancer incidence increased from 378,000 cases per year in 1980 to 454,000 cases per year in 2010 (annual rate of increase, 0.6%). Cervical cancer death rates have been decreasing, but the disease still accounted for 200,000 deaths in 2010; in developing countries, 46,000 of these women were aged 15-49 years, and 109,000 were aged 50 years or older.[45]
Age-related demographics

The Centers for Disease Control and Prevention (CDC) surveillance of screening-detected cancers (colon and rectum, breast, and cervix) in the United States from 2004 to 2006 reported that the incidence of late-stage cervical cancer was highest among women aged 5079 years.[46] However, cervical cancer may be diagnosed in any woman of reproductive age. Indeed, rates of cervical adenocarcinoma have been increasing in women under 40 years of age.[47] These cases are less easily detected with Pap test screening, and survivorship is low because cases tend to be detected at a late stage. Moreover, the HPV types causing adenocarcinoma are different from the types causing squamous carcinoma. HPV 16, which is a stronger carcinogen than other HPV types, has been found more frequently in younger women than in older ones.[48, 49]

Race-related demographics

Racial variation in cervical cancer rates per 100,000 women in the United States, according to Surveillance Epidemiology and End Results (SEER) data from 2005-2009, was as follows:

Hispanic - 11.8 African American - 9.8 American Indian/Alaska Native - 8.1 White - 8.0 Asian/Pacific Islander - 7.2

Except for Asian/Pacific Islanders, women of other races have higher mortality from cervical cancers than their white counterparts in the United States do.[50] Death rates from cervical cancer have been highest among African Americans; however, death rates in AfricanAmerican women decreased by 2.6% per year from 2004 to 2008 while remaining stable in white women.[42]

Prognosis
The prognosis in patients with cervical cancer depends on the disease stage. In general, the 5year survival rates are as follows:

Stage I - Greater than 90% Stage II - 60-80% Stage III - Approximately 50% Stage IV - Less than 30%

The ACS estimates that 4220 women will die of cervical cancer in the United States in 2012.[42] This represents 1.3% of all cancer deaths and 6.5% of deaths from gynecologic cancers.

Patient Education
Cervical cancer is overrepresented among underserved and minority groups in the United States. It is imperative to increase awareness about the benefit of Pap test screening for preventing cervical cancer among women in these groups. Education about the benefit of HPV vaccination is also important but must be accompanied by the information that vaccination does not substitute for regular screening. A Cochrane review found that the best approach to encourage women to undergo cervical screening involved invitations.[51] These may take any of the following forms:

Appointments (fixed or open) Letters Telephone calls Verbal recommendations Prompts Follow-up letters

These findings relate to screening in developed countries, however, and their relevance to developing countries is unclear. Further studies are required to determine the effectiveness of promising interventions, such as revealing in an invitation letter the gender of the smear taker, using a health promotion nurse, employing lay outreach health workers, and carrying out intensive attempts at recruitment

History
Because many women are screened routinely, the most common finding is an abnormal Papanicolaou (Pap) test result. Typically, these patients are asymptomatic. Clinically, the first symptom of cervical cancer is abnormal vaginal bleeding, usually postcoital. Vaginal discomfort, malodorous discharge, and dysuria are not uncommon. The tumor grows by extending along the epithelial surfaces, both squamous and glandular, upward to the endometrial cavity, throughout the vaginal epithelium, and laterally to the pelvic wall. It can invade the bladder and rectum directly, leading to constipation, hematuria, fistula, and ureteral obstruction, with or without hydroureter or hydronephrosis. The triad of leg edema, pain, and hydronephrosis suggests pelvic wall involvement. The common sites for distant metastasis include extrapelvic lymph nodes, liver, lung, and bone.

Physical Examination
In patients with early-stage cervical cancer, physical examination findings can be relatively normal. As the disease progresses, the cervix may become abnormal in appearance, with gross erosion, ulcer, or mass. These abnormalities can extend to the vagina. Rectal examination may reveal an external mass or gross blood from tumor erosion. Bimanual pelvic examination findings often reveal pelvic or parametrial metastasis. If the disease involves the liver, hepatomegaly may develop. Pulmonary metastasis usually is difficult to detect on physical examination unless pleural effusion or bronchial obstruction becomes apparent. Leg edema suggests lymphatic or vascular obstruction caused by tumor.

Approach Considerations
Complete evaluation starts with Papanicolaou (Pap) testing. Positive results should prompt colposcopy and biopsies with further workup of cervical intraepithelial neoplasia (CIN), including excisional procedures. If pathologic evaluation after loop electrosurgical excision or conization suggests invasive cancer with positive margins, the patient should be referred to a gynecologic oncologist. Patients with suspicious or grossly abnormal cervical lesions on physical examination should undergo biopsy regardless of the cytologic findings. Once the diagnosis is established, a complete blood count (CBC) and serum chemistries for renal and hepatic function should be ordered to look for abnormalities from possible metastatic disease, and imaging studies should be performed for staging purposes. In the International Federation of Gynecology and Obstetrics (Federation Internationale de Gynecologie et dObstetrique [FIGO]) guidelines for staging, procedures are limited to the following[52] :

Colposcopy Biopsy Conization of cervix Cystoscopy Proctosigmoidoscopy Chest x-ray

Cystoscopy and proctoscopy should be performed in patients with a bulky primary tumor to help rule out local invasion of the bladder and the colon. Barium enema studies can be used to evaluate extrinsic rectal compression from the cervical mass. In the United States, more complex radiologic imaging studies are often done to guide the choice of therapeutic options. These may include computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET), as well as surgical staging. (See also Cervical Cancer Imaging.)

Screening Recommendations
The American Cancer Society (ACS), the American Society for Colposcopy and Cervical Pathology (ASCCP), and the American Society for Clinical Pathology (ASCP) have issued joint guidelines for cervical cancer screening.[4] In 2012, the US Preventive Services Task Force (USPSTF) issued updated guidelines whose recommendations are consistent with those of the ACS, ASCCP, and ASCP.[5] In November 2012, the American College of Obstetricians and Gynecologists (ACOG) issued new screening guidelines that were also consistent with those of these groups.[2, 3] Screening recommendations for specific patient age groups are as follows[2, 3, 4, 5] :

< 21 years No screening recommended 21-29 years Cytology (Pap smear) alone every 3 years 30-65 years Human papillomavirus (HPV) and cytology cotesting every 5 years (preferred) or cytology alone every 3 years (acceptable) > 65 years No screening recommended if adequate prior screening has been negative and high risk is not present

The USPSTF cautions that positive screening results are more likely with HPV-based strategies than with cytology alone and that some women may have persistently positive HPV results and require prolonged surveillance with additional frequent testing. Similarly, women who would otherwise be advised to end screening at age 65 years on the basis of previously normal cytology results may undergo continued testing because of positive HPV test results.[5] Current US guidelines advise against using HPV testing to screen for cervical cancer in women younger than 30 years; the ACS advises that for screening in women 30-65 years of age, HPV testing alone is not currently recommended for most clinical settings in the US. Annual screening is not recommended at any age or with any method. Women who have had a total hysterectomy may stop undergoing cervical cancer screening. Exceptions are as follows:

Women who had a hysterectomy without removal of the cervix Women who have had a CIN grade 2 or 3 lesion treated in the past 20 years Women who have had cervical carcinoma at any time

Women in whom co-testing shows a negative Pap smear but a positive HPV test should have 12-month follow-up cotesting. Women with atypical squamous cells of undetermined significance (ASCUS) on Pap smear but a negative HPV test can be rescreened with cotesting in 5 years or with cytology alone in 3 years.[4]

Papanicolaou Testing
For many years, the Pap test has been the standard method for cervical cancer screening. Retrospective data have shown that screening with a Pap test reduces the incidence of cervical cancer by 60-90% and the death rate by 90%. Because of false negatives, the best that a Pap test can do is to reduce the incidence of cervical cancer to 2-3 per 100,000 women. False-negative tests mostly result from sampling error, which can be reduced by ensuring that adequate material is taken from both the endocervical canal and the ectocervix. Smears without endocervical or metaplastic cells should be repeated. (See Pap Smear.) The limitations of the conventional Pap test include limited sensitivity (51%) and a significant proportion of inadequate specimens. In addition, accurate interpretation of conventional Pap tests is often compromised by the presence of artifacts (eg, blood, mucus, obscuring inflammation, scant cellular material, or air-drying artifact). Newer liquid-based Pap test technologies have become available. In a randomized, controlled trial from the Netherlands that compared liquid-based and conventional cervical cytology, liquid-based cytology reduced the proportion of unsatisfactory specimens from 1.1% to 0.3% and eliminated obscuring blood, poor fixation, cytolysis, and insufficient spreading of cells as causes of unsatisfactory results.[53] With liquid-based cytology, however, older women (primarily those 55-60 years of age) were more likely to have a sample called unsatisfactory. Nevertheless, 18-month follow-up showed that women with unsatisfactory results by either method were not at higher risk for cervical abnormalities.[53]
ThinPrep Papanicolaou test

Test samples for the ThinPrep Pap test are collected the same way as those for the conventional Pap test. However, the specimen is placed in a preservative solution rather than on a slide. An automated processor prepares the sample and makes a uniform slide for review. Mucus and blood are removed in the process. The ThinPrep Papanicolaou test was approved in 1996 by the US Food and Drug Administration (FDA) as an alternative to the traditional conventional smear.

Human Papillomavirus Testing

The Hybrid Capture II assay for HPV was approved by the FDA in 2003 as a new approach for cervical cancer. This test is useful for interpreting equivocal results from a Pap test. If a woman has a Pap test result showing ASCUS but a subsequent HPV test is negative, she can be rescreened with Pap testing in 3 years; if the HPV test is positive, then additional workup with a colposcopy is indicated. The ACS guidelines favor using HPV testing with cytology in women aged 30 years and older. If both tests are negative, then the next Pap test can be delayed for 5 years.

Imaging Studies for Metastasis

A routine chest radiograph is obtained to help rule out pulmonary metastasis. Chest radiography may be considered optional for disease that is stage IB1 or lower.[9] A CT scan of the abdomen and pelvis is performed to look for metastasis in the liver, lymph nodes, or other organs (see the image below) and to help rule out hydronephrosis or hydroureter. MRI or positron-emission tomography (PET) scanning is an alternative to CT scanning; in fact, PET scanning is now recommended for patients with stage IB2 disease or higher.[9]

CT scan of cervical cell carcinoma demonstrates markedly enlarged lymph node at left pelvic sidewall. This is consistent with pelvic lymph node metastasis, which is indicative of stage IIIB disease. Cystic consistency is not unusual for metastatic cervical carcinoma. Primary tumor is well depicted as hypoattenuating circumscribed mass. Cyst is present in anteriorly located left ovary.

Magnetic resonance whole-body diffusion-weighted imaging scanning has been used to distinguish uterine cervical carcinoma from normal uterine cervix. This technique can also differentiate metastatic nodes from benign nodes.[54] (See also Cervical Cancer Imaging.)

Surgical Staging
Clinical staging protocols can fail to demonstrate pelvic and aortic lymph node involvement in 20-50% and 6-30% of patients, respectively. For that reason, surgical staging sometimes is recommended. Pretreatment surgical staging is the most accurate method of determining the extent of disease. However, there is little evidence to suggest that routine surgical staging yields any significant improvement in overall survival. Therefore, the decision whether to perform pretreatment surgical staging should be made on an individual basis after a thorough

nonsurgical workup, including fine-needle aspiration of lymph nodes, has failed to demonstrate metastatic disease.

Histologic Findings
Precancerous lesions of the cervix usually are detected via a Pap test. The Pap test classification system has evolved over the years. Standardized Pap test reporting emerged from a 1988 workshop sponsored by the National Cancer Institute. Currently, cervical cytology results are reported according to the 2001 Bethesda System.[55]
2001 Bethesda System for reporting cervical cytologic diagnoses

Specimen adequacy may be the single most important quality assurance component of the system. Specimen classifications are as follows:

Satisfactory for evaluation (note presence/absence of endocervical/transformation zone component) Unsatisfactory for evaluation (specify reason) Specimen rejected/not processed (specify reason) Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason)

General categorization (optional) is as follows:

Negative for intraepithelial lesion or malignancy Epithelial cell abnormality Other

Possible interpretations or results are as follows:

Negative for intraepithelial lesion or malignancy Observed organisms (eg, Trichomonas, Candida, bacteria) and cellular changes consistent with herpes simplex virus are reported Reporting other nonneoplastic findings (ie, inflammation and atrophy) is optional Epithelial cell abnormalities Squamous cell Atypical squamous cells (ASC) ASCUS ASC where a high-grade squamous intraepithelial lesion (HSIL) cannot be excluded (ASC-H) Low-grade squamous intraepithelial lesion (LSIL) Encompassing HPV, mild dysplasia, and CIN 1 (see the first image below) HSIL Encompassing moderate and severe dysplasia, carcinoma in situ, CIN 2, and CIN 3 (see the second image below) Squamous cell carcinoma (see the third image below) Glandular cell Atypical glandular cells (AGC) (specify endocervical, endometrial, or not otherwise specified) AGC favoring neoplastic (specify endocervical or not otherwise specified) Endocervical adenocarcinoma in situ (AIS) Adenocarcinoma

Other (list not comprehensive)

Endometrial cells in a woman aged 40 years or older

Cervical intraepithelial neoplasia grade I.

Cervical

intraepithelial neoplasia grade III. carcinoma.

Squamous cell cervical

Automated review and ancillary testing are included as appropriate. Educational notes and suggestions are optional. The histology of cervical malignancy is predominantly that of squamous cell carcinoma, which represents approximately 80% of cases, with adenocarcinomas representing almost 20%. Less common histologies include small cell carcinoma, melanoma, and lymphoma.

FIGO and TNM Staging

There are 2 major staging systems that are frequently used in cervical cancer (see Table 2, below and Cervical Cancer Staging):

The FIGO system, developed in collaboration with the World Health Organization (WHO)[52] The TNM system, developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC)[56]

Table 2. Cervical Cancer Staging: Primary Tumor (T) (Open Table in a new window)
TNM FIGO Stage Stage TX T0 Primary tumor cannot be assessed No evidence of primary tumor

Tis T1 T1a

0 I IA

Carcinoma in situ Cervical carcinoma confined to uterus (extension to corpus should be disregarded) Invasive carcinoma diagnosed only by microscopy. All macroscopically visible lesionseven with superficial invasionare T1b/1B. Stromal invasion with a maximal depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification. Measured stromal invasion 3 mm or less in depth and 7 mm or less in lateral spread Measured stromal invasion more than 3 mm but not more than 5 mm with a horizontal spread 7 mm or less Clinically visible lesion confined to the cervix or microscopic lesion greater than IA2 Clinically visible lesion 4 cm or less in greatest dimension Clinically visible lesion more than 4 cm Cervical carcinoma extends beyond the cervix but not to the pelvic sidewall or to the lower third of vagina Tumor without parametrial invasion Tumor with parametrial invasion Tumor extends to the pelvic wall and/or involves the lower third of the vagina and/or causes hydronephrosis or nonfunctioning kidney Tumor involves lower third of vagina; no extension to pelvic sidewall Tumor extends to pelvic sidewall and/or causes hydronephrosis or nonfunctioning kidney Cervical carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the bladder mucosa or rectal mucosa. Bullous edema does not qualify as a criteria for stage IV disease. Spread to mucosa of adjacent organs (bladder, rectum, or both) Distant metastasis

T1a1 T1a2

IA1 IA2

T1b T1b1

IB IB1 IB2

T2

II

T2a T2b T3

IIA IIB III

T3a T3b

IIIA IIIB

IV

T4 M1

IVA IVB

In the UICC/AJCC system, regional lymph node (N) involvementincluding paracervical, parametrial, hypogastric (obturator), common, internal and external iliac, and presacral and sacral nodesis graded as follows.

NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Regional lymph node metastasis

The T and N grades are combined with the grade for distant metastasis (M) to yield the staging for the cancer (see Table 3, below). Table 3. UICC/AJCC Staging for Cervical Cancer (Open Table in a new window)
Stage Tumor Node Metastasis 0 IA1 IA2 IB1 IIA IIB IIIA IIIB IVA IVB Tis T1a1 T1a2 N0 N0 N0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0

T1b1 N0 T2a T2b T3a T1 T2 T3a T3b T4 N0 N0 N0 N1 N1 N1

Any N M0 Any N M0

Any T Any N M1

Approach Considerations
The treatment of cervical cancer varies with the stage of the disease (see Cervical Cancer Staging). For early invasive cancer, surgery is the treatment of choice. In more advanced cases, radiation combined with chemotherapy is the current standard of care. In patients with disseminated disease, chemotherapy or radiation provides symptom palliation. (See also Cervical Cancer Treatment Protocols.) The treatment of cervical cancer frequently requires a multidisciplinary approach. Involvement of a gynecologic oncologist, radiation oncologist, and medical oncologist may be necessary.

Stage-Based Therapy
Stage 0 cancer

Carcinoma in situ (stage 0) is treated with local ablative or excisional measures such as cryosurgery, laser ablation, and loop excision. Surgical removal is preferred in that it allows further pathologic evaluation to rule out microinvasive disease. After treatment, these patients require lifelong surveillance.
Stage IA1 Cancer

The treatment of choice for stage IA1 disease is surgery. Total hysterectomy, radical hysterectomy, and conization are accepted procedures. Lymph node dissection is not required if the depth of invasion is less than 3 mm and no lymphovascular invasion is noted. Selected patients with stage IA1 disease but no lymphovascular space invasion who desire to maintain fertility may undergo therapeutic conization with close follow-up, including cytology, colposcopy, and endocervical curettage. Patients with comorbid medical conditions who are not surgical candidates can be successfully treated with radiation. According to National Comprehensive Cancer Network (NCCN) guidelines, pelvic radiation therapy is currently a category 1 recommendation for women with stage IA disease and negative lymph nodes after surgery who have high-risk factors (eg, a large primary tumor, deep stromal invasion, or lymphovascular space invasion).[9]
Stage IA2, IB, or IIA cancer

For patients with stage IB or IIA disease, there are 2 treatment options:

Combined external beam radiation with brachytherapy Radical hysterectomy with bilateral pelvic lymphadenectomy

Radical vaginal trachelectomy with pelvic lymph node dissection is appropriate for fertility preservation in women with stage IA2 disease and those with stage IB1 disease whose lesions are 2 cm or smaller.[9] The principal problems with pregnancy after trachelectomy are premature labor and the need to undergo cesarean section for delivery.[57] Most retrospective studies have shown equivalent survival rates for trachelectomy and hysterectomy, though such studies usually are flawed because of patient selection bias and other compounding factors. However, a 2008 study showed identical overall and disease-free survival rates for the 2 procedures.[58] Current surgical guidelines for stage IA2 to IIA cervical cancers allow for minimally invasive techniques, such as traditional laparoscopic and robotically assisted laparoscopic techniques, in the surgical management of these tumors. Indeed, it has been shown that these less morbid procedures are equally effective in achieving adequate surgical margins and lymph node dissection while possessing the added advantage of shorter postoperative recovery times.[59,
60, 61]

An analysis of women from the Surveillance, Epidemiology, and End Results (SEER) database who underwent radical hysterectomy with lymphadenectomy revealed that patients with node-negative early-stage cervical cancer who underwent a more extensive lymphadenectomy had improved survival.[62] Compared with patients who had fewer than 10 nodes removed, patients who had 21-30 nodes removed were 24% less likely to die of their tumors, and those who had more than 30 nodes removed were 37% less likely to die. Postoperative irradiation of the pelvis reduces the risk of local recurrence in patients with high-risk factors (ie, positive pelvic nodes, positive surgical margins, and residual parametrial disease).[63] A randomized trial showed that patients with parametrial involvement, positive pelvic nodes, or positive surgical margins benefit from a postoperative combination of cisplatin-containing chemotherapy and pelvic irradiation.[64] Postoperative radiation therapy is also recommended in patients who have at least 2 intermediate risk factors (including tumor size greater than 2 cm, deep stromal invasion, or lymphovascular space invasion). For patients with IB2 or IIA cancer and tumors larger than 4 cm, radiation and chemotherapy is selected in most cases. Risks are associated with combined therapy, but many of these patients will meet either intermediate- or high-risk criteria after radical hysterectomy and therefore are strong candidates for this approach.
Stage IIB, III, or IVA cancer

For locally advanced cervical carcinoma (stages IIB, III, and IVA), radiation therapy was the treatment of choice for many years. Radiation therapy begins with a course of external beam radiation to reduce tumor mass and thereby enable subsequent intracavitary application. Brachytherapy is delivered by means of afterloading applicators that are placed in the uterine cavity and vagina. Additionally, the results from large, well-conducted, prospective randomized clinical trials have demonstrated a dramatic improvement in survival when chemotherapy is combined with radiation therapy.[65, 66, 67] Consequently, the use of cisplatin-based chemotherapy in combination with radiation has become the standard of care for primary management of patients with locally advanced cervical cancer.[9]
Stage IVB and recurrent cancer

Individualized therapy is used on a palliative basis. Radiation therapy is used alone for control of bleeding and pain, whereas systemic chemotherapy is used for disseminated disease.[9] For recurrent disease, the choice of therapy is influenced by the treatments previously employed. Treatment of pelvic recurrences after primary surgical management should include singleagent chemotherapy and radiation, and treatment for recurrences elsewhere should include combination chemotherapy.[68, 69, 70] For central pelvic recurrence after radiation therapy, modified radical hysterectomy (if the recurrence is smaller than 2 cm) or pelvic exenteration should be undertaken.[71, 72] For disease recurring after chemotherapy and radiation therapy, a disease-free interval of more than 16 months is considered to designate the tumor as platinum-sensitive.[73] The

standard of care in these cases is chemotherapy with a platinum-based doublet of paclitaxel and cisplatin.[69, 70, 74, 75] The NCCN also recommends bevacizumab, docetaxel, gemcitabine, ifosfamide, 5fluorouracil, mitomycin, irinotecan, and topotecan as possible candidates for second-line therapy (category 2B recommendation), as well as pemetrexed and vinorelbine (category 3 recommendation). In addition, bevacizumab as single-agent therapy is also acceptable.[9] In a recent analysis, by the National Cancer Institute (NCI), of the clinical trial Gynecologic Oncology Group (GOG) 240, bevacizumab was found to extend survival by almost 4 months in patients with advanced, recurrent, or persistent cervical cancer that had not responded to standard surgery or radiotherapy.[76] According to the NCI analysis of bevacizumab in cervical cancer patients, median survival was better in women treated with chemotherapy plus bevacizumab, versus those treated with chemotherapy alone. A total of 452 patients with pretreated metastatic, recurrent, or persistent cervical cancer were enrolled in the GOG 240 study from 2009 to 2012. The patients received bevacizumab at a dosage of 15 mg/kg body weight, in conjunction with chemotherapy, 1 day every 3 weeks until disease progression or unacceptable toxicity occurred.[76] Recurrences arising in a previously irradiated field or after a disease-free interval of less than 16 months are less likely to respond to subsequent therapies. Consequently, patients with such recurrences should be strongly encouraged to participate in clinical trials. Special efforts should be made to ensure that they receive comprehensive palliative care, including adequate pain control.

Complications of Therapy
Radiation-related complications

During the acute phase of pelvic radiation therapy, the surrounding normal tissues (eg, intestines, bladder, and perineal skin) often are affected. Acute adverse gastrointestinal (GI) effects include diarrhea, abdominal cramping, rectal discomfort, and bleeding. Diarrhea can usually be controlled by giving either loperamide or atropine sulfate. Small steroid-containing enemas are prescribed to alleviate symptoms from proctitis. Cystourethritis also can occur, leading to dysuria, frequency, and nocturia. Antispasmodics often are helpful for symptom relief. Urine should be examined for possible infection. If urinary tract infection (UTI) is diagnosed, therapy should be instituted without delay. Proper skin hygiene should be maintained for the perineum. Topical lotion should be used if erythema or desquamation occurs. Late sequelae of radiation therapy usually appear 1-4 years after treatment. The major sequelae include rectal or vaginal stenosis, small bowel obstruction, malabsorption, radiation enteritis,and chronic cystitis.

Surgical complications

The most frequent complication of radical hysterectomy is urinary dysfunction resulting from partial denervation of the detrusor muscle. Other complications include foreshortened vagina, ureterovaginal fistula, hemorrhage, infection, bowel obstruction, stricture and fibrosis of the intestine or rectosigmoid colon, and bladder and rectovaginal fistulas. Invasive procedures (eg, nephrostomy or diverting colostomy) sometimes are performed in this group of patients to improve their quality of life.

Nutrition
Proper nutrition is important for patients with cervical cancer. Every attempt should be made to encourage and provide adequate oral food intake. Nutritional supplements (eg, Ensure [Abbott Nutrition, Columbus, OH] or Boost [Nestl HealthCare Nutrition, Fremont, MI]) are used when patients have had significant weight loss or cannot tolerate regular food because of nausea caused by radiation or chemotherapy. In patients with severe anorexia, appetite stimulants such as megestrol can be prescribed. For patients who are unable to tolerate any oral intake, percutaneous endoscopic gastrostomy tubes are placed for nutritional supplementation. In patients with extensive bowel obstruction as a result of metastatic cancer, hyperalimentation sometimes is used.

Prevention of Human Papillomavirus Infection

Human papillomavirus (HPV) infection is usually transmitted sexually, though rare cases have been reported in virgins.[77] Condom use may not prevent transmission.[78, 77] A study in a mouse model by Roberts et al found that a widely used vaginal spermicide, nonoxynol-9, greatly increased susceptibility to HPV infection, whereas carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection.[79] Evidence suggests that HPV vaccines prevent HPV infection.[6] PATRICIA (PApilloma TRIal against Cancer In young Adults) found HPV 16/18 vaccine to be efficacious against cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ, irrespective of the HPV type in the lesion.[80] Cross-protective efficacy was demonstrated against 4 oncogenic HPV types not included in the vaccine.[81] Use of an HPV 6/11/16/18 vaccine reduced the risk of any high-grade cervical lesions by 19.0% overall, irrespective of causal HPV type.[79] The following 2 HPV vaccines are approved by the US Food and Drug Administration (FDA):

Gardasil (Merck, Whitehouse Station, NJ) This quadrivalent vaccine is approved for girls and women 9 to 26 years of age to prevent cervical cancer (and also genital warts and anal cancer) caused by HPV types 6, 11, 16, and 18; it is also approved for males 9 to 26 years of age[7] Cervarix (GlaxoSmithKline, Research Triangle Park, NC) This bivalent vaccine is approved for girls and women 9 through 25 years of age to prevent cervical cancer caused by HPV types 16 and 18[8]

The Advisory Committee on Immunization Practices (ACIP) recommends routine HPV vaccination of girls aged 11-12 years with 3 doses of either HPV vaccine. The vaccination series can be started as young as age 9 years. Catch-up vaccination is recommended for females aged 13-26 years who have not been previously vaccinated or who have not completed the full series.[82] The ACIP also recommends routine use of quadrivalent HPV vaccine in boys aged 11-12 years, as well as in males aged 13-21 years who have not been vaccinated previously or who have not completed the 3-dose series. Males aged 22-26 years may also be vaccinated.[83] Screening for cervical cancer should continue in vaccinated women, following the same guidelines as in unvaccinated women.[4] These vaccines do not provide complete protection against cervical cancer; oncogenic HPV types other than 16 and 18 account for about 30% of cases, and cross-protection may be only partial. In addition, not all vaccinated patients may mount an effective response to the vaccine, particularly if they do not receive all 3 doses or if they get the doses at time intervals that are not associated with efficacy. Finally, the duration of protection with these vaccines has not yet been determined. The available evidence suggests that immunity from infection with the HPV types covered by these vaccines will persist for at least 6-8 years,[84] but continuing follow-up will be required to determine whether revaccination will be necessary. The safety of HPV vaccines is a deeply controversial topic. Follow-up of large patient populations who participated in phase 3 clinical trials has documented that both FDAapproved HPV vaccines are extremely safe. Articles in the popular media, however, have detailed cases of young women with devastating illness attributed to the vaccines. In postlicensure safety surveillance for the quadrivalent HPV vaccine, 6.2% of all reports to the Vaccine Adverse Event Reporting System (VAERS) described serious adverse events, including neurologic injury (eg, Guillain-Barr syndrome) and 32 reports of death. In comparison with other vaccines, rates of most of these adverse events were no greater than the background rates, but there was disproportional reporting of syncope and venous thromboembolic events

Medication Summary
Chemotherapy should be administered in conjunction with radiation therapy to most patients with stage IB (high-risk) to stage IVA cervical cancer. Cisplatin is the agent used most commonly, although 5-fluorouracil also is used frequently. For patients with metastatic disease, cisplatin remains the most active agent. Topotecan, ifosfamide, and paclitaxel also have significant activity in this setting. The combination of topotecan and cisplatin improves overall survival. However, acute toxicities are also increased.

Chemotherapy Agents, Alkylating

Class Summary

Alkylating chemotherapy agents inhibit cell growth and proliferation. They inhibit DNA synthesis through the formation of DNA cross-links.

View full drug information Cisplatin (Platinol)

Intrastrand cross-linking of DNA and inhibition of DNA precursors are among the proposed mechanisms of action for cisplatin. This agent is used in combination with radiation therapy.
View full drug information Ifosfamide (Ifex)

Ifosfamide forms DNA interstrand and intrastrand bonds that interfere with protein synthesis. Although the US Food and Drug Administration (FDA) has approved this agent only for the treatment of testicular cancer, it has several off-label indications, including treatment of cervical cancer.

Antineoplastics, Antimetabolite
Class Summary

Antimetabolite antineoplastic agents inhibit cell growth and proliferation. They interfere with DNA synthesis by blocking the methylation of deoxyuridylic acid.
View full drug information Fluorouracil (Adrucil)

Fluorouracil is a pyrimidine antimetabolite. Several mechanisms of action have been proposed, including inhibition of thymidylate synthase and inhibition of RNA synthesis. This agent is also a potent radiosensitizer.

Antineoplastics, Antimicrotubular
Class Summary

Antimicrotubular antineoplastic agents prevent cell growth and proliferation. They work by enhancing tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly.
View full drug information Paclitaxel (Taxol)

The mechanisms of action of paclitaxel are tubulin polymerization and microtubule stabilization. This agent also participates in the breakage of chromosomes and modulation of immune response.

Antineoplastics, Topoisomerase Inhibitors

Class Summary

Topoisomerase-inhibiting antineoplastic agents prevent cell growth and proliferation. They work by binding to topoisomerase and causing single-strand DNA breaks.
View full drug information Topotecan (Hycamtin)

Topotecan inhibits topoisomerase I, inhibiting DNA replication. It acts in the S phase of the cell cycle. Patients who have received prior chemotherapy should be given a lower dose initially.

Vaccines, Inactivated, Viral

Class Summary

Two human papillomavirus (HPV) vaccines are now available for prevention of HPVassociated dysplasias and neoplasias, including cervical cancer, genital warts (condylomata acuminata), and precancerous genital lesions. The immunization series should be completed in girls and young women aged 9-26 years.[8] The duration of protection is not yet known, but follow-up to date has found sustained immunogenicity and efficacy more than 8 years after vaccination.
View full drug information Human papillomavirus vaccine, quadrivalent (Gardasil)

The quadrivalent recombinant HPV vaccine is indicated to prevent disorders secondary to infection from HPV types 6, 11, 16, and 18, including cervical cancer, genital warts (condylomata acuminata), and the following precancerous genital lesions:

Cervical adenocarcinoma in situ Cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3 Vulvar intraepithelial neoplasia grades 2 and 3 Vaginal intraepithelial neoplasia grades 2 and 3

The efficacy of the vaccine is mediated by humoral immune responses following the immunization series.
View full drug information Human papillomavirus vaccine, bivalent (Cervarix)

The bivalent recombinant HPV vaccine is prepared from the L1 protein of HPV types 16 and 18. It is indicated for girls and women (ages 9-25 years) to prevent the following diseases caused by oncogenic HPV types 16 and 18:

Cervical cancer CIN grade 2 or higher Cervical adenocarcinoma in situ CIN grade 1

Medicinenet.

Vaginal Cancer
February 26, 2013 What is vaginal cancer?

Vaginal cancer is a disease in which malignant (cancer) cells form in the vagina. The vagina is the canal leading from the cervix (the opening of uterus) to the outside of the body. At birth, a baby passes out of the body through the vagina (also called the birth canal). Vaginal cancer is not common. When found in early stages, it can often be cured. There are two main types of vaginal cancer:

Squamous cell carcinoma: Cancer that forms in squamous cells, the thin, flat cells lining the vagina. Squamous cell vaginal cancer spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer. It is found most often in women aged 60 or older. Adenocarcinoma: Cancer that begins in glandular (secretory) cells. Glandular cells in the lining of the vagina make and release fluids such as mucus. Adenocarcinoma is more likely than squamous cell cancer to spread to the lungs and lymph nodes. It is found most often in women aged 30 or younger.

What are causes and risk factors for vaginal cancer?

Age and exposure to the drug DES (diethylstilbestrol) before birth affect a woman's risk of developing vaginal cancer. Anything that increases your risk of getting a disease is called a risk factor. Risk factors for vaginal cancer include the following:

Being aged 60 or older. Being exposed to DES while in the mother's womb. In the 1950s, the drug DES was given to some pregnant women to prevent miscarriage (premature birth of a fetus that cannot survive). Women who were exposed to DES before birth have an increased risk of developing vaginal cancer. Some of these women develop a rare form of cancer called clear cell adenocarcinoma.

Having human papilloma virus (HPV) infection. Having a history of abnormal cells in the cervix or cervical cancer.

What are symptoms and signs of vaginal cancer?

Possible signs of vaginal cancer include pain or abnormal vaginal bleeding. Vaginal cancer often does not cause early symptoms and may be found during a routine Pap test. When symptoms occur they may be caused by vaginal cancer or by other conditions. A doctor should be consulted if any of the following problems occur:

Bleeding or discharge not related to menstrual periods. Pain during sexual intercourse. Pain in the pelvic area. A lump in the vagina.

What tests are used to diagnose vaginal cancer?

Tests that examine the vagina and other organs in the pelvis are used to detect (find) and diagnose vaginal cancer. The following tests and procedures may be used:

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken. Pelvic exam: An exam of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. The doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and places the other hand over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. A speculum is also inserted into the vagina and the doctor or nurse looks at the vagina and cervix for signs of disease. A Pap test or Pap smear of the cervix is usually done. The doctor or nurse also inserts a lubricated, gloved finger into the rectum to feel for lumps or abnormal areas. Pap smear: A procedure to collect cells from the surface of the cervix and vagina. A piece of cotton, a brush, or a small wooden stick is used to gently scrape cells from the cervix and vagina. The cells are viewed under a microscope to find out if they are abnormal. This procedure is also called a Pap test. Biopsy: The removal of cells or tissues from the vagina and cervix so they can be viewed under a microscope by a pathologist to check for signs of cancer. If a Pap smear shows abnormal cells in the vagina, a biopsy may be done during a colposcopy. Colposcopy: A procedure in which a colposcope (a lighted, magnifying instrument) is used to check the vagina and cervix for abnormal areas. Tissue samples may be taken using a curette (spoon-shaped instrument) and checked under a microscope for signs of disease.

What is the prognosis for vaginal cancer?

Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery) depends on the following:

The stage of the cancer (whether it is in the vagina only or has spread to other areas). The size of the tumor. The grade of tumor cells (how different they are from normal cells). Where the cancer is within the vagina. Whether there are symptoms. The patient's age and general health. Whether the cancer has just been diagnosed or has recurred (come back).

Treatment options depend on the following:

The stage, size, and location of the cancer. Whether the tumor cells are squamous cell or adenocarcinoma. Whether the patient has a uterus or has had a hysterectomy. Whether the patient has had past radiation treatment to the pelvis.

How is staging determined for vaginal cancer?

After vaginal cancer has been diagnosed, tests are done to find out if cancer cells have spread within the vagina or to other parts of the body. The process used to find out if cancer has spread within the vagina or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following procedures may be used in the staging process:

Biopsy: A biopsy may be done to find out if cancer has spread to the cervix. A sample of tissue is cut from the cervix and viewed under a microscope. A biopsy that removes only a small amount of tissue is usually done in the doctor's office. A woman may need to go to a hospital for a cone biopsy (removal of a larger, cone-shaped piece of tissue from the cervix and cervical canal). A biopsy of the vulva may also be done to see if cancer has spread there. Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. Cystoscopy: A procedure to look inside the bladder and urethra to check for abnormal areas. A cystoscope is inserted through the urethra into the bladder. A cystoscope is a thin, tubelike instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer. Ureteroscopy: A procedure to look inside the ureters to check for abnormal areas. A ureteroscope is inserted through the bladder and into the ureters. A ureteroscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease. A ureteroscopy and cystoscopy may be done during the same procedure. Proctoscopy: A procedure to look inside the rectum to check for abnormal areas. A proctoscope is inserted through the rectum. A proctoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue to be checked under a microscope for signs of disease. CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI). Lymphangiogram: A procedure used to x-ray the lymph system. A dye is injected into the lymph vessels in the feet. The dye travels upward through the lymph nodes and lymph vessels and x-rays are taken to see if there are any blockages. This test helps find out whether cancer has spread to the lymph nodes.

The following stages are used for vaginal cancer: Stage 0 (carcinoma in situ) In stage 0, squamous cell cancer is found in tissue lining the inside of the vagina. Stage 0 cancer is also called carcinoma in situ. Stage I In stage I, cancer is found only in the vagina. Stage II In stage II, cancer has spread from the vagina to the tissue around the vagina. Stage III In stage III, cancer has spread from the vagina to the lymph nodes in the pelvis or groin, or to the pelvis, or both. Stage IV Stage IV is divided into stage IVA and stage IVB:

Stage IVA: Cancer may have spread to lymph nodes in the pelvis or groin and has spread to one or both of the following areas: o The lining of the bladder or rectum. o Beyond the pelvis. Stage IVB: Cancer has spread to parts of the body that are not near the vagina, such as the lungs. Cancer may also have spread to the lymph nodes.

Recurrent vaginal cancer Recurrent vaginal cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the vagina or in other parts of the body.
What is the treatment for vaginal cancer?

There are different types of treatment for patients with vaginal cancer. Different types of treatments are available for patients with vaginal cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before

starting treatment, patients may want to think about taking part in a clinical trial. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team. Three types of standard treatment are used: Surgery Surgery is the most common treatment of vaginal cancer. The following surgical procedures may be used:

Laser surgery: A surgical procedure that uses a laser beam (a narrow beam of intense light) as a knife to make bloodless cuts in tissue or to remove a surface lesion such as a tumor. Wide local excision: A surgical procedure that takes out the cancer and some of the healthy tissue around it. Vaginectomy: Surgery to remove all or part of the vagina. Total hysterectomy: Surgery to remove the uterus, including the cervix. If the uterus and cervix are taken out through the vagina, the operation is called a vaginal hysterectomy. If the uterus and cervix are taken out through a large incision (cut) in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a small incision in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy. Lymphadenectomy: A surgical procedure in which lymph nodes are removed and checked under a microscope for signs of cancer. This procedure is also called lymph node dissection. If the cancer is in the upper vagina, the pelvic lymph nodes may be removed. If the cancer is in the lower vagina, lymph nodes in the groin may be removed. Pelvic exenteration: Surgery to remove the lower colon, rectum, and bladder. In women, the cervix, vagina, ovaries, and nearby lymph nodes are also removed. Artificial openings (stoma) are made for urine and stool to flow from the body into a collection bag.

Skin grafting may follow surgery, to repair or reconstruct the vagina. Skin grafting is a surgical procedure in which skin is moved from one part of the body to another. A piece of healthy skin is taken from a part of the body that is usually hidden, such as the buttock or thigh, and used to repair or rebuild the area treated with surgery. Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to increase the chances of a cure, is called adjuvant therapy. Radiation therapy Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation

therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated. Chemotherapy Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can affect cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated. Topical chemotherapy for squamous cell vaginal cancer may be applied to the vagina in a cream or lotion. New types of treatment are being tested in clinical trials. These include the following: Radiosensitizers Radiosensitizers are drugs that make tumor cells more sensitive to radiation therapy. Combining radiation therapy with radiosensitizers may kill more tumor cells.
Treatment options by stage

Stage 0 Vaginal Cancer (carcinoma in situ) Treatment of vaginal squamous cell carcinoma in situ may include the following:

Wide local excision, with or without a skin graft. Partial or total vaginectomy, with or without a skin graft. Topical chemotherapy. Laser surgery. Internal radiation therapy.

Stage I Vaginal Cancer Treatment of stage I squamous cell vaginal cancer may include the following:

Internal radiation therapy, with or without external radiation therapy to lymph nodes or large tumors. Wide local excision or vaginectomy with vaginal reconstruction. Radiation therapy may be given after the surgery. Vaginectomy and lymphadenectomy, with or without vaginal reconstruction. Radiation therapy may be given after the surgery.

Treatment of stage I vaginal adenocarcinoma may include the following:

Vaginectomy, hysterectomy, and lymphadenectomy. This may be followed by vaginal reconstruction and/or radiation therapy. Internal radiation therapy, with or without external radiation therapy to lymph nodes. A combination of therapies that may include wide local excision with or without lymphadenectomy and internal radiation therapy.

Stage II Vaginal Cancer Treatment of stage II vaginal cancer is the same for squamous cell cancer and adenocarcinoma. Treatment may include the following:

Both internal and external radiation therapy to the vagina, with or without external radiation therapy to lymph nodes. Vaginectomy or pelvic exenteration, with or without radiation therapy.

Stage III Vaginal Cancer Treatment of stage III vaginal cancer is the same for squamous cell cancer and adenocarcinoma. Treatment may include both internal and external radiation therapy, with or without surgery. Stage IVA Vaginal Cancer Treatment of stage IVA vaginal cancer is the same for squamous cell cancer and adenocarcinoma. Treatment may include both internal and external radiation therapy, with or without surgery. Stage IVB Vaginal Cancer Treatment of stage IVB vaginal cancer is the same for squamous cell cancer and adenocarcinoma. Treatment may include the following:

Radiation therapy as palliative therapy, to relieve symptoms and improve the quality of life. Chemotherapy may also be given. A clinical trial of chemotherapy and/or radiosensitizers.

Treatment options for recurrent vaginal cancer

Treatment of recurrent vaginal cancer may include the following:

Pelvic exenteration. Radiation therapy. A clinical trial of a new treatment.

St Helens & Knowsley Teaching Hospitals

Vaginal cancer is a rare type of cancer. The most common symptom of vaginal cancer is painless bleeding from the vagina.
The vagina

The vagina is a tube of muscle that runs from the cervix (the opening of the womb) to the vulva (the external sexual organs). The vagina has three main functions:

It provides a channel through which blood released during menstruation (a period) can leave the body. It provides a channel that allows a baby to leave the womb during childbirth. It contains a large number of nerve endings that help stimulate feelings of sexual pleasure during intercourse.

Types of vaginal cancer

There are two main types of vaginal cancer:

primary vaginal cancer, where the cancer begins inside the vagina, and secondary vaginal cancer, where the cancer begins in another part of the body (usually the reproductive system), such as the cervix or ovaries, and then spreads to the vagina.

The rest of this article will focus on primary vaginal cancer. See Useful links for more information about other cancers of the reproductive system.
Types of primary vaginal cancer

There are three main types of primary vaginal cancer. They are classified according to the type of cells that the cancer begins in.

Squamous cell carcinoma is the most common type of vaginal cancer, accounting for 85% of all cases. It usually develops in women over 50. Clear cell adenocarcinoma accounts for 9% of all cases of vaginal cancer. This type of cancer usually affects teenagers and younger adults, with most cases developing in women between 14 and 20 years old. Melanoma is rare and accounts for up to 2% of all cases of primary vaginal cancer. As with squamous cell carcinoma, melanoma usually develops in women over 50.

How common is vaginal cancer?

Vaginal cancer is rare and accounts for one in every 1,000 cases of cancer overall. Each year in England and Wales, there are an average of 200 new cases of vaginal cancer. The exact causes of vaginal cancer are unknown, but possible risk factors include:

smoking, and being infected with the human papilloma virus (HPV).

Outlook

The outlook for squamous cell carcinoma and clear cell adenocarcinoma is generally good if the cancer is detected when it is still contained within the vagina. An estimated 7080% of women with early-stage vaginal cancer live for at least five years after receiving a diagnosis, and many women will live much longer. The outlook for the melanoma type of vaginal cancer is poor because it is very aggressive and spreads quickly. Only 1520% of women live for five years or more after diagnosis. Vaginal cancer can be treated with a combination of radiotherapy, surgery and chemotherapy.

Uterus The uterus, also known as the womb, is a hollow, pear-shaped organ in a woman where a baby grows during pregnancy.

Causes of vaginal cancer Diagnosing vaginal cancer Treating vaginal cancer Complications of vaginal... Preventing vaginal cancer

Symptoms of vaginal cancer

The most common symptom of vaginal cancer is painless vaginal bleeding. If you are pre-menopausal (you still have regular periods), the bleeding may occur in between your normal periods. You may also notice that your period is much heavier than usual. Some women with vaginal cancer also experience vaginal bleeding after sexual intercourse. Less common symptoms of vaginal cancer include:

pain when urinating (dysuria), a sudden, urgent need to urinate, blood in the urine, and pelvic pain.

When to seek medical advice

See your GP if:

you experience vaginal bleeding and you have already had the menopause, your usual pattern of menstruation has changed, such as having irregular or heavier periods than usual, or you experience problems with urination, such as pain when urinating.

While it is highly unlikely that these symptoms are due to vaginal cancer, they still need to be investigated by your GP.
Glossary Discharge Discharge is when a liquid such as pus oozes from a part of your body. Pain Pain is an unpleasant physical or emotional feeling and your body's way of warning you that it has been damaged. Constipation Constipation is when you pass stools less often than usual, or when you have difficulty going to the toilet because your stools are hard and small. Cervical smear test During a cervical smear test, a sample of cells from a womans cervix is taken and examined for abnormalities. Inflammation Inflammation is the body's response to infection, irritation or injury. It causes redness, swelling, pain and sometimes a feeling of heat in the affected area.

Diagnosing vaginal cancer Treating vaginal cancer Complications of vaginal... Preventing vaginal cancer

Causes of vaginal cancer

How does cancer begin?

Cancer begins with a change in the structure of DNA, which is found in all human cells. DNA provides cells with a basic set of instructions, such as when to grow and when to reproduce. A change in the DNA's structure (genetic mutation) changes these instructions so that the cells carry on growing and reproducing uncontrollably. This produces a lump of tissue known as a tumour.
How does cancer spread?

Left untreated, cancer can quickly grow and spread to other parts of the body, usually through the lymphatic system.

The lymphatic system is a series of glands (or nodes) located throughout your body. It is similar to the blood circulatory system. Lymph glands produce many specialised cells that are needed by your immune system to fight infection. Once the cancer reaches the lymphatic system, it can spread to any other part of the body, including your bones, blood and organs.
Risk factors

The exact cause of vaginal cancer has not yet been identified. However, evidence suggests that a number of risk factors can increase your likelihood of developing vaginal cancer:
Human papilloma virus (HPV)

Human papilloma virus (HPV) is the name given to a family of viruses that affect the skin and the moist membranes that line the body, such as those in the cervix, anus, mouth and throat. HPV DNA has been found in up to 80% of samples of cancerous tissue, which suggests that HPV may increase your risk of developing vaginal cancer. HPV is known to cause changes in the cells of the cervix, which can lead to cervical cancer. It is thought that the virus could have a similar effect on the cells of the vagina. HPV is spread during sexual intercourse, including anal and oral sex. See Useful links for more information about HPV.
Diethylstilbestrol (DES)

The medicine diethylstilbestrol (DES) is another known risk factor for vaginal cancer. DES was widely prescribed for pregnant women from 1938 to 1971. At the time, it was thought (wrongly) that DES could help reduce the risk of miscarriage. In 1971, researchers discovered a link between DES and cancer and the use of DES in pregnant women was banned. The risk of vaginal cancer associated with using DES is small. It is estimated that only one in every 1,000 women whose mothers used DES during pregnancy go on to develop vaginal cancer.
Other possible risk factors

Other possible risk factors for vaginal cancer include:

smoking, a history of reproductive cancers, such as cervical or ovarian cancer, and alcohol consumption.

Glossary Uterus The uterus, also known as the womb, is a hollow, pear-shaped organ in a woman where a baby grows during pregnanc

Treating vaginal cancer Complications of vaginal... Preventing vaginal cancer

Diagnosing vaginal cancer

Before diagnosing vaginal cancer, your GP will ask you about your symptoms and the pattern of your vaginal bleeding. They may refer you for blood tests to rule out other causes of vaginal bleeding, such as infection or an overactive thyroid gland (hyperthyroidism).
Referral to a gynaecologist

If no obvious cause of your symptoms can be found, your GP will probably refer you to a gynaecologist for further testing. A gynaecologist is a specialist in treating conditions of the female reproductive system. If you are referred to a gynaecologist, further tests will probably include:

an internal vaginal examination to look for any unusual lumps or swellings, and a colposcopy, using a special instrument (colposcope) that acts like a magnifying glass, to study your vagina in greater detail.

If testing reveals that there may be abnormal tissue inside your vagina, a small sample of the tissue will be removed and checked under a microscope for cancerous cells. This is known as a biopsy.
Further testing

If the results of the biopsy suggest that you have cancer, and there is a risk that the cancer may have spread, you will probably require further testing to assess how widespread the cancer is. These tests may include:

X-rays, computerised tomography (CT) scans, and magnetic resonance imaging (MRI) scans.

Glossary Tissue Body tissue is made up of groups of cells that perform a specific job, such as protecting the body against infection, producing movement or storing fat.

Lymph nodes Lymph nodes are small oval tissues that remove unwanted bacteria and particles from the body. They are part of the immune system. Biopsy A biopsy is a test that involves taking a small sample of tissue from the body so it can be examined. Blood Blood supplies oxygen to the body and removes carbon dioxide. It is pumped around the body by the heart. MRI MRI (magnetic resonance imaging) is the use of magnets and radiowaves to take detailed pictures of inside the body. Colposcopy A colposcopy is a procedure where a doctor uses a special magnifying lens, known as a colposcope, to look at the cervix through the opening of the vagina

Complications of vaginal... Preventing vaginal cancer

Treating vaginal cancer

Cancer treatment team

Many primary care trusts (PCTs) have multi-disciplinary teams (MDTs) that treat vaginal cancer. See box, right. If you have vaginal cancer, you may see several or all of these professionals as part of your treatment. Deciding what treatment is best for you can be difficult. Your cancer team will make recommendations, but the final decision will be yours. Before going to hospital to discuss your treatment options, you may find it useful to write a list of questions to ask the specialist. For example, you may want to find out what the advantages and disadvantages of particular treatments are.
Staging

Health professionals use a staging system to describe how far vaginal cancer has advanced.

Stage 0. Cancer has not developed but the cells in the vagina are showing signs that they may turn cancerous in the future. This is also known as vaginal intraepithelial neoplasia (VAIN). Stage 1. The cancer is contained inside the vagina. Stage 2. The cancer is beginning to spread through the walls of the vagina towards the pelvic bones. Stage 3. The cancer has spread into the bones of the pelvis and may have spread to nearby lymph nodes. Stage 4a. The cancer has spread beyond the pelvis and into the linings of the bladder and bowel. Stage 4b. The cancer has spread into the bladder and bowel. Stage 4c. The cancer had spread to other organs, such as the lungs.

In stage 0 vaginal cancer, it may be possible to remove the abnormal cells using laser surgery or a special type of ointment. In stage 1 vaginal cancer, it may be possible to achieve a cure using radiotherapy alone and/or by removing a small section of the vagina. In stages 2, 3 and 4a vaginal cancer, a combination of radiotherapy, chemotherapy and surgery may be required to get rid of the cancer. In stages 4b and 4c vaginal cancer, a cure is not usually possible. However, radiotherapy and chemotherapy can relieve the symptoms and slow down the spread of cancer.
Radiotherapy

There are several ways that radiotherapy can be used to treat vaginal cancer. It can be used:

as an initial treatment to cure the cancer, in combination with chemotherapy (chemoradiation), after surgery to prevent the cancer from returning, and to control symptoms when a cure is not possible (palliative radiotherapy).

There are two ways that radiotherapy for vaginal cancer can be given:

external radiotherapy, where a machine beams high-energy rays at your vagina, and internal radiotherapy, where a small radioactive device, known as a source, which looks like a tampon is inserted into your vagina.

The type of radiotherapy you receive depends on where the cancer is in the body. Many women receive a combination of internal and external radiotherapy. External radiotherapy is usually given in short daily sessions from Monday to Friday, with a break from treatment at the weekend. With internal radiotherapy, you usually need to keep the source in your vagina for between two and five days.

While it kills cancerous cells, radiotherapy can also affect healthy tissue and has a number of side effects, including:

sore, red skin (like sunburn), vaginal discharge, pain while passing urine, loss of taste, loss of appetite, tiredness, and nausea.

If you have external radiotherapy to the pelvis, you may experience an early menopause (if you have not had the menopause already). See Useful links for more information about radiotherapy. Menopausal symptoms include:

hot flushes, vaginal dryness, dry skin, mood changes, such as feeling anxious or depressed, and loss of interest in sex (low libido) .

If you have an early menopause, you will no longer be able to have children.
Surgery

There are four different types of surgery that are used to treat vaginal cancer:

partial vaginectomy, where the upper section of the vagina is surgically removed, radical vaginectomy, where most or all of the vagina is surgically removed, radical vaginectomy and radical hysterectomy, where the vagina and womb, ovaries and fallopian tubes are surgically removed, along with nearby lymph nodes, and total pelvic exenteration, where the vagina, bladder, rectum (back passage) and part of the bowel are removed.

Partial vaginectomy

A partial vaginectomy can be used to treat stage 1 vaginal cancer, where radiotherapy has failed to remove the cancer or where a woman prefers to have surgery rather than radiotherapy because she still wants to have children. The surgeon will remove the cancerous section of the vagina, as well as a 35mm margin of healthy tissue, in case a small number of cancer cells have spread. The rest of the vagina is stretched up and stitched into place, so you will be able to have normal sexual intercourse after you have recovered from the operation.

A radical vaginectomy

A radical vaginectomy is used to treat cases of advanced stage 1 and stage 2 vaginal cancer. The surgeon will remove most or all of your vagina. A plastic surgeon will be able to make a new vagina using skin, muscle and tissue taken from another part of your body, usually one of your thighs or buttocks. This operation is known as vaginal reconstruction. After the operation, you will still be able to have sex, although it is unlikely that you will be able to achieve an orgasm during intercourse. This is because the many nerve endings that are normally within the vagina will no longer be there. You will need to use artificial lubrication during sex because the reconstructed vagina will not be naturally lubricated. However, your clitoris (a sensitive part of the female genitals) should be unaffected, so you should be able to achieve an orgasm through masturbation and oral sex.
A radical hysterectomy

A radical hysterectomy is used when testing shows there is a high risk that cancerous cells have spread beyond the vagina and into other parts of the reproductive system. During a radical hysterectomy, all of the reproductive system is removed, including the womb, fallopian tubes, ovaries and nearby lymph nodes. See Useful links for more information about hysterectomy.
Total pelvic exenteration (TPE)

A total pelvic exenteration (TPE) is used to treat advanced cases of vaginal cancer. TPE is major surgery, so you will need to be in good health before the procedure can be performed. If you are not, surgery may have to be delayed until your health improves. The surgeon will remove your vagina, bladder, rectum and part of the colon. Because you will no longer have a bladder, you will need another way to pass urine. One solution is for your surgeon to make a hole (stoma) in your abdomen. A bag is then attached to the stoma so that urine can be passed into it. The bag is known as a urostomy bag. Similarly, as you will no longer have a rectum, you will need a way to pass stools (faeces) out of your digestive system. Another stoma can be made and attached to a collection bag, known as a colostomy bag. See Useful links for more information about colostomies. It may be possible to reconstruct your rectum and attach it to the remaining section of colon once this has healed. In this case, you will only need a temporary colostomy. As TPE is major surgery, it may take you several months to fully recover from the operation.

Chemotherapy

Chemotherapy is usually used in combination with radiotherapy or to control symptoms when a cure is not possible (called palliative chemotherapy). Chemotherapy is usually given by injection (called intravenous chemotherapy). Like radiotherapy, the powerful cancer-killing medicines used in chemotherapy can also damage healthy tissue and cause a range of side effects. Side effects of chemotherapy include:

nausea, vomiting, hair loss, and fatigue.

Chemotherapy can also weaken your immune system, making you more vulnerable to infection. However, the side effects should stop once treatment has finished. See Useful links for more information about chemotherapy.
Clinical trials

As vaginal cancer is rare, you may be asked to take part in a clinical trial. Clinical trials are an important way for health professionals to learn more about the best way to treat specific conditions. Most clinical trials involve comparing a new treatment with an existing treatment to determine whether the new treatment is more or less effective. If you do receive a new treatment, there is no guarantee that it will be more effective than an existing one. Your care team can tell you if there are clinical trials in your area, and explain the advantages and disadvantages of taking part. For more information on clinical trials, see Clinical trials and medical research
Glossary Uterus The uterus, also known as the womb, is a hollow, pear-shaped organ in a woman where a baby grows during pregnancy. Bladder The bladder is a small organ near the pelvis that holds urine until it is ready to be passed from the body. Radiotherapy

Radiotherapy uses X-rays to treat disease, especially cancer. Chemotherapy Chemotherapy is the treatment of an illness or disease with a chemical substance, for example in the treatment of cance

Preventing vaginal cancer

Complications of vaginal cancer

Emotional effects of treatment

Treatment for vaginal cancer can have a significant emotional impact, particularly in women who have not yet reached the menopause and need to have radiotherapy or a hysterectomy. Both these treatments trigger an early menopause, which means that many women have to come to terms with the fact that they will never be able to have children. This can be particularly traumatic for women with clear cell adenocarcinoma because they are usually teenagers when the cancer develops. The removal of some or all of the vagina can be traumatic for pre- and post-menopausal women alike, and many women feel less 'womanly' than before. It is not uncommon to feel a sense of loss and bereavement after treatment and, in some women, this may trigger the start of depression. Talking to other women who have had similar treatment can give you emotional support and reassurance. Your GP or the hospital staff may be able to recommend a suitable local support group. If feelings of depression persist, your GP can arrange further treatment.

Preventing vaginal cancer

HPV vaccination

There is a strong link between certain types of human papilloma virus (HPV) and the development of abnormalities that may develop into vaginal cancer. There is now a vaccine that provides protection against the two strains of HPV that are thought to be responsible for most cases of vaginal cancer. HPV vaccination also protects against cervical cancer, which is far more common than vaginal cancer. Girls should be offered the HPV vaccine as part of their routine childhood immunisation programme. The vaccine should be given to girls who are 12 to 13 years old, with three doses given over six months.

The HPV vaccine will not provide protection against all strains of HPV. As HPV is spread through unprotected sex, using a condom is the best way to avoid it. Before beginning a sexual relationship with a new partner, it is a good idea for you both to be tested for sexually transmitted infections (STIs) at a sexual health (GUM) clinic. All tests are free and confidential. See Useful links for more information about the HPV vaccination and to find your a sexual health clinic in your area

St Helens & Knowsley Teaching Hospitals

NHS Cervical Screening Programme

Cervical screening is not a test for diagnosing cancer but a way of detecting abnormalities which, if left untreated, could lead to cervical cancer. Early detection and treatment can prevent cancer developing in women who attend regularly when invited. Women are invited to join the cervical screening programme from the age of 25 to 49 every three years and 50 to 64 every five years.

Macmillan Cancer Support 1 April 2012 The womb is a muscular, pear-shaped organ at the top of the vagina. The lining of the womb is shed each month, which results in bleeding called a period. If a woman becomes pregnant, her periods stop temporarily, then theyll normally continue until she goes through the menopause. Close to the cervix is a collection of lymph nodes.

Causes and risk factors

Each year, over 2,900 women are diagnosed with cervical cancer in the UK. It usually occurs in women over the age of 20. The highest rates occur between the ages of 30-39, but it can also affect younger and older women. Cancer of the cervix can take many years to develop. Before it does, changes occur in the cells of the cervix. These changes are known as cervical intrapepithelial neoplasia (CIN). The abnormal cells are not cancerous, but some doctors refer to the changes to these cells as precancerous. This means that the cells might develop into cancer in some women if they are not treated. But most women with CIN do not develop cancer, and if treatment is needed for CIN its nearly always effective.

Causes and risk factors

Each year, over 2,900 women are diagnosed with cervical cancer in the UK. It usually occurs in women over the age of 20. The highest rates occur between the ages of 30-39, but it can also affect younger and older women. Cancer of the cervix can take many years to develop. Before it does, changes occur in the cells of the cervix. These changes are known as cervical intrapepithelial neoplasia (CIN). The abnormal cells are not cancerous, but some doctors refer to the changes to these cells as precancerous. This means that the cells might develop into cancer in some women if they are not treated. But most women with CIN do not develop cancer, and if treatment is needed for CIN its nearly always effective. Our section about cervical screening has more detailed information about CIN and its treatment.

Can screening prevent cervical cancer?

Our video explains how doctors use cervical screening to help to prevent cancer.

Risk factors for cervical cancer

HPV and sex

CIN is usually the result of an infection from the human papilloma virus (HPV). HPV is a very common virus that can affect the cells of the cervix. Its mainly passed on during sex. Having sex at an early age and having several sexual partners can increase the risk of catching HPV and developing cervical cancer. But many women who have only had one sexual partner have HPV at some point in their life, and may go on to develop CIN or cervical cancer. So theres no reason for you or others to feel that youre to blame for having cervical cancer. We have more detailed information about HPV and cancer,.

Smoking

Women who smoke are more likely to develop CIN and the most common type of cervical cancer, known as squamous cell cervical cancer.
A weakened immune system

Having a weakened immune system may allow CIN to develop into cancer. The immune system can be weakened by smoking, a poor diet and infections such as HIV/AIDS.
Contraceptive pill

Long-term use of the contraceptive pill (for more than 10 years) can slightly increase the risk of developing cervical cancer. But for most women the benefits of taking the pill outweigh the risks. Cancer of the cervix is not infectious and cant be passed on to other people

Preventing cervical cancer

Regular screening is the best way to reduce the risk of cervical cancer. There are also two vaccines that can help prevent cervical cancer.

Vaccines Back to top

Two vaccines are now available in the UK to prevent HPV infection Gardasil and Cervarix. There are more than 100 types of HPV, and each type is identified by a number. Both of the vaccines have been shown to protect against HPV 16 and 18, which are high-risk types. It is hoped that the vaccines will prevent at least 7 out of 10 cases (70%) of the most common type of cervical cancer (squamous cell cervical cancer). These vaccines work best if they are given to children before puberty and before they might start having sex. For this reason, all 1213-year-old girls in the UK are now routinely offered a HPV vaccination. The vaccines can also be obtained privately.

Cervical screening Back to top

This is an important way of detecting early changes in cells of the cervix so that treatment can be given to prevent a cancer developing. It involves taking a sample of cells from the cervix using a test known as a liquid-based cytology. In the UK, the NHS provides cervical screening tests for all women within a specific age range who are registered with a GP. The age range for screening varies across the UK. In England and Northern Ireland screening takes place between the ages of 2564, in Scotland its between the ages of 20-60, and in Wales its between the ages of 2064. If abnormal cells are found during your cervical screening test, you will be referred for a colposcopy to have a biopsy taken.

Symptoms of cervical cancer

Very early-stage cervical cancer may have no symptoms. This means its important to attend regular cervical screening, so that any cell changes can be picked up early. The most common symptom of cervical cancer is abnormal vaginal bleeding, usually between periods or after sex. Women whove gone through the menopause (who are no longer having periods) may find they have some new bleeding. Symptoms of cervical cancer can also include a smelly vaginal discharge and discomfort during sex. If youre attending regular screening, you should let your GP know if you develop symptoms between your tests

How cervical cancer is diagnosed

Usually you begin by seeing your family doctor (GP), who will examine you and refer you to the hospital for any necessary tests and for specialist gynaecological advice and treatment.
On this page

Colposcopy Large loop excision of the transformation zone Needle excision of the transformation zone (NETZ) Cone biopsy

If your GP suspects you may have cancer, you should be seen at the hospital within 14 days.

Colposcopy Back to top

A colposcopy can be carried out by a specialist doctor or a nurse colposcopist and is usually done in a hospital outpatient clinic. In a colposcopy, a specially adapted type of microscope with a light, called a colposcope, is used to show the cervix in detail. It acts like a magnifying glass so that the nurse or doctor can make a thorough examination of the abnormal cells of the cervix. The test takes about 1520 minutes. Before your test youll be helped to position yourself on a specially designed chair or examination table. In the same way as when you had the screening test, the nurse or doctor will use a speculum to hold the vagina open. The doctor or nurse may first repeat the screening test. The cervix is then painted with a liquid to make the abnormal areas show up more clearly. A light is shone onto the cervix and the nurse or doctor looks through the colposcope to examine the area in detail.

A small sample of surface cells (a biopsy) will be taken from the cervix and examined under a microscope by a pathologist in the laboratory. It may be slightly painful when the biopsy is taken, and for a short time afterwards. Taking a mild painkiller can help with this. Having a biopsy may also cause a bit of light bleeding for a few days afterwards.

Large loop excision of the transformation zone Back to top

If the abnormal area cant be seen properly with a colposcope, you may have a LLETZ procedure. Sometimes the LLETZ may be done during your colposcopy appointment. Abnormal cells are most likely to develop in an area of the cervix known as the transformation zone. A LLETZ is a common procedure that removes the abnormal cells. Having a LLETZ normally takes about 5-10 minutes. Its usually done under a local anaesthetic as an outpatient at the hospital. Once youre in a comfortable position, the doctor will put some local anaesthetic onto your cervix to numb it. The doctor uses a colposcope to see a magnified image of your cervix. A thin wire, which is shaped in a loop, is then used to cut away the affected area. The procedure may feel uncomfortable and its usual to have slight bleeding or discharge, which can last for a few weeks after this treatment. You may be asked not to use tampons or have sex for a month afterwards.

Needle excision of the transformation zone (NETZ) Back to top

This is similar to a LLETZ, except that the thin wire used to cut away the affected area is straight, rather than in a loop. The straight wire acts like a knife and enables the doctor to cut away the precise area of affected tissue.

Cone biopsy Back to top

Sometimes a procedure known as a cone biopsy may be used if the abnormal area in the cervix cant be seen with a colposcope. A cone biopsy is usually done under a general anaesthetic, although a local anaesthetic may sometimes be used. You may need to stay in hospital overnight.

Area of cone biopsy shown by dotted line View a large version of the image

A small, cone-shaped section of the cervix is removed, which is large enough to contain the abnormal cells. If theres only a very small growth of cancer cells (known as a microinvasive cancer), the cone biopsy may remove it all so that no further treatment is needed. Even if the cone biopsy doesnt remove all the cancer cells, its still useful, as it will help the doctors decide on the right type of treatment for you. After a cone biopsy a gauze pack, which is like a tampon, may be placed in your vagina to prevent bleeding. This is usually removed within 24 hours, before you go home. You may also have a thin tube, called a catheter, put into your bladder so that you can pass urine while the gauze pack is in place. Its normal to have some light bleeding for a few weeks after a cone biopsy. Strenuous physical activity and sex should be avoided for four weeks to allow the cervix to heal.

It may take some time for you to get the results of these tests. You could ask your gynaecologist about when and how youll be told about whether you need more tests or treatment. Its a difficult time for most women and you may need support from family, friends or support organisations while youre waiting for your results.

ests after diagnosis of cervical cancer

Your gynaecologist will need to do some further tests to check your general health and see whether the cancer has spread beyond the cervix.
On this page

Blood tests Chest x-ray Examination under anaesthetic (EUA) CT (computerised tomography) scan MRI (magnetic resonance imaging) scan PET/CT scan

The tests may include any of the following:

Blood tests Back to top

A sample of blood is taken to check the number of cells in your blood (your blood count), and to see how well your kidneys and liver are working.

Chest x-ray Back to top

This is to check that your lungs and heart are healthy.

Examination under anaesthetic (EUA) Back to top

This is an examination of the vagina and cervix under a general anaesthetic. It allows the doctor to examine you thoroughly without it being uncomfortable. The doctor may also look into your bladder and the lower end of your large bowel (the colon and rectum) to see if the cancer has spread. To look into your bladder the doctor will use a cystoscope, which is a small, fibre-optic tube with a light. If there are any abnormal areas, the doctor can use the cystoscope to take biopsies. To look into the lower end of the colon and the rectum, the doctor uses a similar tube called a proctosigmoidoscope. The proctosigmoidoscope is also used to take biopsies from any abnormal areas. You may have some slight bleeding for a couple of days after this examination. Your healthcare professional will be able to give you more information about the examination and what to expect afterwards.

CT (computerised tomography) scan Back to top

A CT scan takes a series of x-rays, which build up a three-dimensional picture of the inside of the body. The scan takes 10-30 minutes and is painless. It uses a small amount of radiation, which is very unlikely to harm you and will not harm anyone you come into contact with. You will be asked not to eat or drink for at least 3-4 hours before the scan.

A CT scan takes 10-30 minutes View a larger version of the CT scan image

You may be given a drink or injection of a dye, which allows particular areas to be seen more clearly. This may make you feel hot all over for a few minutes. Its important to let your doctor know if youre allergic to iodine or have asthma, because you could have a more serious reaction to the injection. Youll probably be able to go home as soon as the scan is over.

MRI (magnetic resonance imaging) scan Back to top

This test uses magnetism to build up a detailed picture of areas of your body. The scanner is a powerful magnet, so you may be asked to complete and sign a checklist to make sure its safe for you. The checklist asks about any metal implants you may have, for example a pacemaker, surgical clips or bone pins. You should also tell your doctor if youve ever worked with metal or in the metal industry, as very tiny fragments of metal can sometimes lodge in the body. If you do have any metal in your body, its likely that you wont be able to have an MRI scan. In this situation another type of scan can be used. Before the scan youll be asked to remove any metal belongings, including jewellery. Some people are given an injection of dye into a vein in the arm, which doesnt usually cause discomfort. This is called a contrast medium and can help the images from the scan to show up more clearly. During the test youll lie very still on a couch inside a long cylinder (tube) for about 30 minutes. Its painless but can be slightly uncomfortable, and some people feel a bit claustrophobic. Its also noisy, but youll be given earplugs or headphones. Youll be able to hear, and speak to, the person operating the scanner.

PET/CT scan Back to top

This is a combination of a CT scan, which takes a series of x-rays to build up a threedimensional picture, and a positron emission tomography (PET) scan, which uses low-dose radiation to measure the activity of cells in different parts of the body. PET/CT scans give more detailed information about the part of the body being scanned. You may have to travel to a specialist centre to have a PET/CT scan. You wont be able to eat for six hours before the scan, although you may be able to have a drink. At least an hour before the scan, a mildly radioactive substance is injected into a vein, usually in your arm. The radiation dose used is very small. The scan itself usually takes 30-90 minutes. You should be able to go home after the scan. It will probably take several days for the results of these tests to be ready. The waiting period will obviously be an anxious time for you. You may find it helpful to talk things over with your clinical nurse specialist, or with a relative or close friend. You can also contact one of our cancer support specialists, or a support organisation.

Types of cervical cancer

There are two main types of cervical cancer.

The most common is called squamous cell carcinoma. This develops from the flat cells that cover the outer surface of the cervix at the top of the vagina. The other type is called adenocarcinoma. This type develops from the glandular cells that line the cervical canal (the endocervix). As adenocarcinoma starts in the cervical canal, it can be more difficult to detect with cervical screening tests.

There are also other, less common types of cancer of the cervix, known as adenosquamous carcinomas, clear-cell carcinomas and small-cell carcinomas. Our cancer support specialists can give you more information about these types of cervical cancer. The tests will show which type of cervical cancer you have. They can also give information about the stage of the cancer and whether there are signs of microscopic cancer cells in the lymph or blood vessels. This information, as well as the physical examination and the results of further tests, will help your doctors decide which type of treatment is best for you.

Staging of cervical cancer

The stage of a cancer is a term used to describe its size and whether it has spread beyond the area of the body where it first started.
On this page

Stage 1 Stage 2 Stage 3 Stage 4

Knowing the extent of the cancer helps the doctors decide on the most appropriate treatment for you. Cervical cancer is divided into four main stages. Each stage then has further sub-divisions.

Stage 1 Back to top

The cancer cells are only within the cervix. Stage 1 can be further divided into:
Stage 1A

The cancer can only be seen with a microscope or colposcope.

Stage 1A1

The cancer is 3mm or less deep and 7mm or less wide.

Stage 1A2

The cancer is between 35mm deep and 7mm or less wide.

Stage 1B

The cancer growth is larger but still confined to the cervix.

Stage 1B1

The cancer is not larger than 4cm.

Stage 1B2

The cancer is larger than 4cm.

Stage 2 Back to top

The cancer has spread into surrounding structures, such as the upper part of the vagina or the tissues next to the cervix. Stage 2 can be further divided into:
Stage 2A

The cancer has spread into the upper part of the vagina.
Stage 2A1

The tumour size is not larger than 4cm.

Stage 2A2

The tumour size is larger than 4cm.

Stage 2B

The cancer has spread into the tissues next to the cervix.

Stage 3 Back to top

The cancer has spread to areas such as the lower part of the vagina, or the tissues at the sides of the pelvic area. Stage 3 can be further divided into:
Stage 3A

The cancer has spread into the lower part of the vagina.
Stage 3B

The cancer has spread through to the tissues at the sides of the pelvic area and may be pressing on one of the ureters (the tubes urine passes through from the kidneys to the bladder). If the tumour is causing pressure on a ureter, there may be a build-up of urine in the kidney.

Stage 4 Back to top

The cancer has spread to the bladder or bowel or beyond the pelvic area. Stage 4 can be further divided into:
Stage 4A

The cancer has spread to nearby organs, such as the bladder and bowel.
Stage 4B

The cancer has spread to distant organs, such as the lungs, liver or bone. Your doctors may use the following terms to describe your cancer:

Early-stage cervical cancer - this usually includes stages 1A to 2A. Locally advanced cervical cancer - this usually includes stages 2B to 4A. Advanced-stage cervical cancer - this usually means stage 4B.

If the cancer comes back after initial treatment, this is known as recurrent cancer.

Treatment for cervical cancer

Cancer of the cervix can be treated with either surgery, radiotherapy, chemotherapy or a combination of these treatments.
On this page

Early-stage cancer Locally advanced cancer Advanced-stage cancer Planning your treatment Giving your consent The benefits and disadvantages of treatment Second opinion

Your doctor will advise you on the best plan of treatment for you, taking into account a number of factors. These include your age and general health, and the type and stage of the cancer.

Early-stage cancer Back to top

Surgery

Surgery is often the main treatment for women with early-stage cancer of the cervix.

Radiotherapy

Radiotherapy is as effective as surgery for early-stage cancer and may be used as an alternative to surgery. Sometimes radiotherapy may also be given after surgery if theres a risk that cancer cells may have been left behind. This helps reduce the risk of the cancer coming back. Radiotherapy rather than surgery is usually used to treat larger tumours in the cervix (tumours over 4cm). This is because its often not possible to completely remove a larger tumour with surgery alone, whereas radiotherapy treatment can be very effective. Radiotherapy is often given in combination with chemotherapy treatment for larger tumours. This is known as chemoradiation. Its thought that the chemotherapy makes cervical cancer more sensitive to the effects of the radiotherapy, so that the treatment is more effective.

Locally advanced cancer Back to top

Chemoradiation

This is the main treatment for locally advanced cancer.

Surgery

Very occasionally, an operation known as a pelvic exenteration may be carried out if the cancer has spread to nearby organs in the pelvis (such as the bladder or bowel), but not to distant organs (such as the lungs). This type of surgery involves a major operation and is only suitable for a small number of women.

Advanced-stage cancer Back to top

Chemotherapy

This may be used to treat cancer that has spread to more distant parts of the body, such as the liver and lungs. Chemotherapy can help to shrink and control the cancer and relieve symptoms, to prolong a good quality of life. This is known as palliative treatment.

Planning your treatment Back to top

In most hospitals, a team of specialists will work together to decide which treatment is best for you. This multidisciplinary team (MDT) will include:

a gynaecological oncologist (a surgeon who specialises in gynaecological cancers) a clinical oncologist (a doctor who specialises in treating cancer with radiotherapy and chemotherapy)

a medical oncologist (a doctor who specialises in treating cancer with chemotherapy) a specialist nurse, who will be your main contact and will make sure you get help and support throughout your treatment.

The MDT may also include other healthcare professionals, such as a radiographer (a person who operates the machine that gives radiotherapy treatment), dietitian, physiotherapist, occupational therapist, psychologist or counsellor. The MDT will take a number of factors into account when advising you on the best course of action. These factors include your age, general health, the type and size of the tumour, and whether the cancer has begun to spread. If two treatments are equally effective for your type and stage of cancer, your doctors may offer you a choice of treatments. Sometimes people find it hard to make a decision. If youre asked to make a choice, make sure you have enough information about the different options, whats involved and the possible side effects, so that you can decide on the right treatment for you. Remember to ask questions about any aspects that you dont understand or feel worried about. It may help to discuss the benefits and disadvantages of each option with your cancer specialist, your nurse specialist or our cancer support specialists. If you have any questions about your treatment, dont be afraid to ask your doctor or nurse. It often helps to make a list of questions and to take a relative or close friend with you.

Giving your consent Back to top

Before you have any treatment, your doctor will explain its aims. They will usually ask you to sign a form saying that you give permission (consent) for the hospital staff to give you the treatment. No medical treatment can be given without your consent and before youre asked to sign the form you should be given full information about:

the type and extent of the treatment its advantages and disadvantages any significant risks or side effects any other treatments that may be available.

If you dont understand what youve been told, let the staff know straight away so they can explain again. Some cancer treatments are complex, so its not unusual for people to need explanations repeated. Its a good idea to have a relative or friend with you when the treatment is explained, to help you remember the discussion. You may also find it useful to write a list of questions before your appointment. People sometimes feel that hospital staff are too busy to answer their questions but its important for you to know how the treatment is likely to affect you. The staff should be willing to make time for your questions.

You can always ask for more time if you feel that you cant make a decision when your treatment is first explained to you. You are also free to choose not to have the treatment. The staff can explain what may happen if you dont have it. Its essential to tell a doctor or the nurse in charge, so they can record your decision in your medical notes. You dont have to give a reason for not wanting treatment but it can help to let the staff know your concerns so they can give you the best advice.

The benefits and disadvantages of treatment Back to top

Many people are frightened at the idea of having cancer treatments, particularly because of the possible side effects. However, these can usually be controlled with medicines. Treatment can be given for different reasons, and the potential benefits will vary depending upon the individual situation. In women with early-stage cervical cancer, treatment is given with the aim of curing the cancer. With advanced cancer (cancer that has spread to distant organs), treatment is usually given to control the cancer rather than to cure it. The aim is to improve symptoms and give a better quality of life. However, for some women the treatment will have little effect on the cancer and they will have the side effects without a great deal of benefit. If youve been offered treatment that aims to cure your cancer, deciding whether to accept it may not be difficult. However, if a cure is not possible and the purpose of treatment is to control the cancer for a period of time, it may be more difficult to decide whether to go ahead. Making decisions about treatment in these circumstances is always difficult, and you may need to discuss in detail with your doctor whether you wish to have treatment. If you choose not to have it, you can still be given supportive (palliative) care, with medicines to control any symptoms.

Second opinion Back to top

Your multidisciplinary team uses national treatment guidelines to decide the most suitable treatment for you. Even so, you may want another medical opinion. If you feel it will be helpful, you can ask either your specialist or GP to refer you to another specialist for a second opinion. Getting a second opinion may delay the start of your treatment, so you and your doctor need to be confident that it will give you useful information. If you do go for a second opinion, it may be a good idea to take a relative or friend with you and have a list of questions ready, so that you can make sure your concerns are covered during the discussion

Treatment for cervical cancer

Cancer of the cervix can be treated with either surgery, radiotherapy, chemotherapy or a combination of these treatments.
On this page

Early-stage cancer Locally advanced cancer Advanced-stage cancer Planning your treatment Giving your consent The benefits and disadvantages of treatment Second opinion

Your doctor will advise you on the best plan of treatment for you, taking into account a number of factors. These include your age and general health, and the type and stage of the cancer.

Early-stage cancer Back to top

Surgery

Surgery is often the main treatment for women with early-stage cancer of the cervix.
Radiotherapy

Radiotherapy is as effective as surgery for early-stage cancer and may be used as an alternative to surgery. Sometimes radiotherapy may also be given after surgery if theres a risk that cancer cells may have been left behind. This helps reduce the risk of the cancer coming back. Radiotherapy rather than surgery is usually used to treat larger tumours in the cervix (tumours over 4cm). This is because its often not possible to completely remove a larger tumour with surgery alone, whereas radiotherapy treatment can be very effective. Radiotherapy is often given in combination with chemotherapy treatment for larger tumours. This is known as chemoradiation. Its thought that the chemotherapy makes cervical cancer more sensitive to the effects of the radiotherapy, so that the treatment is more effective.

Locally advanced cancer Back to top

Chemoradiation

This is the main treatment for locally advanced cancer.

Surgery

Very occasionally, an operation known as a pelvic exenteration may be carried out if the cancer has spread to nearby organs in the pelvis (such as the bladder or bowel), but not to distant organs (such as the lungs). This type of surgery involves a major operation and is only suitable for a small number of women.

Advanced-stage cancer Back to top

Chemotherapy

This may be used to treat cancer that has spread to more distant parts of the body, such as the liver and lungs. Chemotherapy can help to shrink and control the cancer and relieve symptoms, to prolong a good quality of life. This is known as palliative treatment.

Planning your treatment Back to top

In most hospitals, a team of specialists will work together to decide which treatment is best for you. This multidisciplinary team (MDT) will include:

a gynaecological oncologist (a surgeon who specialises in gynaecological cancers) a clinical oncologist (a doctor who specialises in treating cancer with radiotherapy and chemotherapy) a medical oncologist (a doctor who specialises in treating cancer with chemotherapy) a specialist nurse, who will be your main contact and will make sure you get help and support throughout your treatment.

The MDT may also include other healthcare professionals, such as a radiographer (a person who operates the machine that gives radiotherapy treatment), dietitian, physiotherapist, occupational therapist, psychologist or counsellor. The MDT will take a number of factors into account when advising you on the best course of action. These factors include your age, general health, the type and size of the tumour, and whether the cancer has begun to spread. If two treatments are equally effective for your type and stage of cancer, your doctors may offer you a choice of treatments. Sometimes people find it hard to make a decision. If youre asked to make a choice, make sure you have enough information about the different options, whats involved and the possible side effects, so that you can decide on the right treatment for you. Remember to ask questions about any aspects that you dont understand or feel worried about. It may help to discuss the benefits and disadvantages of each option with your cancer specialist, your nurse specialist or our cancer support specialists. If you have any questions about your treatment, dont be afraid to ask your doctor or nurse. It often helps to make a list of questions and to take a relative or close friend with you.

Giving your consent Back to top

Before you have any treatment, your doctor will explain its aims. They will usually ask you to sign a form saying that you give permission (consent) for the hospital staff to give you the treatment. No medical treatment can be given without your consent and before youre asked to sign the form you should be given full information about:

the type and extent of the treatment its advantages and disadvantages any significant risks or side effects any other treatments that may be available.

If you dont understand what youve been told, let the staff know straight away so they can explain again. Some cancer treatments are complex, so its not unusual for people to need explanations repeated. Its a good idea to have a relative or friend with you when the treatment is explained, to help you remember the discussion. You may also find it useful to write a list of questions before your appointment. People sometimes feel that hospital staff are too busy to answer their questions but its important for you to know how the treatment is likely to affect you. The staff should be willing to make time for your questions. You can always ask for more time if you feel that you cant make a decision when your treatment is first explained to you. You are also free to choose not to have the treatment. The staff can explain what may happen if you dont have it. Its essential to tell a doctor or the nurse in charge, so they can record your decision in your medical notes. You dont have to give a reason for not wanting treatment but it can help to let the staff know your concerns so they can give you the best advice.

The benefits and disadvantages of treatment Back to top

Many people are frightened at the idea of having cancer treatments, particularly because of the possible side effects. However, these can usually be controlled with medicines. Treatment can be given for different reasons, and the potential benefits will vary depending upon the individual situation. In women with early-stage cervical cancer, treatment is given with the aim of curing the cancer. With advanced cancer (cancer that has spread to distant organs), treatment is usually given to control the cancer rather than to cure it. The aim is to improve symptoms and give a better quality of life. However, for some women the treatment will have little effect on the cancer and they will have the side effects without a great deal of benefit.

If youve been offered treatment that aims to cure your cancer, deciding whether to accept it may not be difficult. However, if a cure is not possible and the purpose of treatment is to control the cancer for a period of time, it may be more difficult to decide whether to go ahead. Making decisions about treatment in these circumstances is always difficult, and you may need to discuss in detail with your doctor whether you wish to have treatment. If you choose not to have it, you can still be given supportive (palliative) care, with medicines to control any symptoms.

Second opinion Back to top

Your multidisciplinary team uses national treatment guidelines to decide the most suitable treatment for you. Even so, you may want another medical opinion. If you feel it will be helpful, you can ask either your specialist or GP to refer you to another specialist for a second opinion. Getting a second opinion may delay the start of your treatment, so you and your doctor need to be confident that it will give you useful information. If you do go for a second opinion, it may be a good idea to take a relative or friend with you and have a list of questions ready, so that you can make sure your concerns are covered during the discussion

Radiotherapy for cervical cancer

Radiotherapy treats cancer by using high-energy x-rays, which destroy the cancer cells while doing as little harm as possible to normal cells.
On this page

External radiotherapy Internal radiotherapy

Radiotherapy for cancer of the cervix can be external or internal, and is often given as a combination of the two. Treatment with radiotherapy may last for 5-8 weeks. Your cancer specialist (clinical oncologist), who plans your treatment, will discuss your treatment in detail with you. Radiotherapy may be given to treat early-stage cervical cancer. Its also usually given for larger tumours contained in the cervix, or if the cancer has spread beyond the cervix and is not curable with surgery alone. Radiotherapy may also be used after surgery if there is a high risk that the cancer may come back. Its often given in combination with chemotherapy (called chemoradiation). Radiotherapy treatment for cervical cancer will affect the ovaries. For younger women who are still having their monthly periods, radiotherapy will stop the ovaries producing eggs and the hormones oestrogen and progesterone. This will make you infertile, so that its no longer possible to have a child. It will also bring on an early menopause, usually about three months after the treatment starts. Your healthcare team will discuss this with you before your treatment starts. They will also be able to give you information about treatments to help you

cope with menopausal symptoms, and options for preserving your fertility if youd like to have a child. Some women may be offered an operation before radiotherapy to reposition their ovaries higher in the abdomen, out of the radiotherapy site. The aim of this surgery is to prevent an early menopause, as the ovaries wont be affected by the radiotherapy treatment. Its known as ovarian transposition and is usually carried out at the same time as initial surgery if its thought that radiotherapy will be needed afterwards. It may also be possible to have an ovarian transposition using laparoscopic (keyhole) surgery. For some women, ovarian transposition isnt successful and an early menopause still happens.

External radiotherapy Back to top

External radiotherapy is normally given as an outpatient, as a series of short daily treatments in the hospital radiotherapy department. High-energy x-rays are directed from a machine (called a linear accelerator) at the area of the cancer.
Planning your treatment

Planning is a very important part of your treatment and may take a few visits. It makes sure that your treatment is as effective as possible. On your first visit to the radiotherapy department youll have a CT scan, which will take images of the area to be treated. These images are used to plan the precise area of treatment. Once the treatment area has been decided, some small tattoo markings are made on your skin. These help the radiographer (the person who gives you your treatment) ensure that youre in the correct position for your treatment. The marks are permanent, but they are the size of a pinpoint and youll only have them if you give your permission. Its a little uncomfortable while the tattoo is being done, but its a good way of making sure that treatment is directed accurately.
Having your treatment

The treatments are usually given from Monday-Friday, with a rest at the weekend. Occasionally if youve missed a treatment due to illness or a bank holiday, you may be asked to have two treatments on the same day (6-8 hours apart). The number of treatments will depend on the type and size of the cancer, but the whole course of external radiotherapy will usually last 5-6 weeks. Your doctor or radiographer will discuss the treatment and possible side effects with you. Before each session of radiotherapy, the radiographer will position you carefully on the couch and make sure that you are comfortable. During your treatment you will be left alone in the room, but youll be able to talk to the radiographer who will be able to see you from the next room. The treatment itself will only last a few minutes.

Positioning the radiotherapy machine

External radiotherapy isnt painful, but you do have to lie still for a few minutes during treatment. The treatment will not make you radioactive and its perfectly safe for you to be with other people, including children, afterwards.

Positioning the radiotherapy machine View a large version of the imagee

Internal radiotherapy Back to top

Internal radiotherapy (also called brachytherapy) gives radiation directly to the cervix and the area close by. Its usually given following external radiotherapy. The treatment may be given as an inpatient or outpatient. To give brachytherapy, a piece of radioactive material called a source is put close to the cancer or, if youve had surgery, the area where the cancer was before it was removed. The source is placed inside specially designed hollow tubes called applicators. A brachytherapy machine is used to place the source into the applicators and to deliver the radiotherapy.

Intrauterine brachytherapy

If youve not had a hysterectomy, you will have intrauterine brachytherapy. A doctor inserts the applicators into the vagina and passes them up through the cervix into the womb. Sometimes additional applicators are placed alongside the cervix. The applicators are inserted in an operating room while youre sedated or under a general anaesthetic. Occasionally a spinal anaesthetic may be used - your doctor will be able to tell you more about this. To prevent the applicators moving, a pack of cotton/gauze padding is placed inside the vagina. Occasionally a piece of gauze is also placed inside the back passage (rectum), and you may have a catheter put into your bladder to drain off urine. While the applicators remain in place during treatment they can be uncomfortable, so you will usually need painkillers to ease any discomfort.
Intravaginal brachytherapy

If you have had a hysterectomy, a single larger hollow tube applicator is placed in the vagina. With intravaginal brachytherapy you wont need an anaesthetic or sedation to insert the applicator and padding isnt necessary. Youll have an MRI scan, CT scan or x-rays to check the position of the applicators. Once its confirmed that the applicators are in the correct position, they are connected to the brachytherapy machine. The machine is then used to place the source into the applicators and deliver the radiotherapy treatment. Brachytherapy may be given in several short bursts or in one long slow treatment, depending on the systems used. There are several different systems in use, and theyre described over the next few pages.
High-dose rate treatment

This is the most common way of giving brachytherapy to the cervix in the UK. With highdose rate treatment, a machine containing a radioactive source of iridium or cobalt is used to give a high dose of radioactivity over a few minutes. High-dose rate treatment may be given as an inpatient or outpatient. How high-dose rate treatments are given varies from hospital to hospital. Your radiotherapy team will be able to tell you exactly how your treatment will be given. Usually the treatment takes about 10-15 minutes and is repeated several times, a few days apart. For example, you may have treatment four times over several days while youre an inpatient. The applicators are usually removed between treatments, but in a few hospitals theyre left in place between treatments and then removed after the final treatment. Alternatively the treatment may be given as an outpatient or day case on three or four occasions over several days or a week. If you have your treatment as an outpatient, the applicators are removed before you go home. A plastic tube may be left in your cervix to help your radiotherapy team position the applicators for your next treatment. You may have a tube (catheter) put into the bladder to drain urine during high-dose rate treatment.

Low-dose rate treatment

Low-dose rate treatment is usually given over 12-24 hours as an inpatient, but sometimes it may be given over a few days. One type of brachytherapy machine thats used to give lowdose rate treatment is known as a Selectron. A Selectron places a radioactive source of small balls of caesium into the applicator tubes to deliver the treatment. The applicators are usually left in place until the treatment has finished. You will be asked to stay in bed to make sure that the applicators stay in the right position. You will also have a urinary catheter. It can be uncomfortable while the applicators remain in place, so youll usually be given regular strong painkillers until the treatment has finished and the applicators have been removed. They put everything near me like food, water. I had a book. There was a TV in the room and I could move my head and my arms.

Youll be cared for in a single room. This is to prevent other people being exposed to radioactivity while the machine is delivering the treatment. However, the radioactive source can be withdrawn from the applicators back into the brachytherapy machine if a nurse or doctor needs to come into the room. This keeps the dose of radioactivity to the nurses and doctors as low as possible. Visitors are usually restricted and children arent encouraged to visit while youre having your treatment. The safety measures and visiting restrictions might make you feel isolated, worried and depressed at a time when you might want people around you. If you have these feelings, its important to tell someone so that you can get some support. It might also help to take in plenty of things to read, an MP3 player and other things to keep you occupied while youre in isolation. You only need to be in isolation while the applicators are in place. Once theyre removed the radioactivity disappears and its perfectly safe to be with other people. The applicators will be removed by one of the doctors or nurses and this may be a bit uncomfortable. Youll be given painkillers beforehand. To make it easier for you, sometimes you might be sedated or given gas (nitrous oxide) and air, known as Entonox.

Pulsed-dose rate brachytherapy

In this treatment the applicators stay in place for the same length of time as low-dose rate treatment, but the radiation dose is given in pulses rather than as a continuous low dose.

Chemotherapy for cervical cancer

Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. There are several chemotherapy drugs that can be used to treat cervical cancer.
On this page

Early-stage and locally advanced cervical cancer Advanced-stage cancer Side effects

The most commonly used drug is cisplatin, which is often given in combination with radiotherapy or in combination with other chemotherapy drugs. The drugs are usually given intravenously (by injection into a vein).

Early-stage and locally advanced cervical cancer Back to top

Chemotherapy may be used to treat larger tumours that are just in the cervix or those that have spread locally (to the surrounding area). Its commonly combined with radiotherapy to make the radiotherapy more effective this is called chemoradiation. Usually the chemotherapy is given once a week during the course of radiotherapy.

Advanced-stage cancer Back to top

Chemotherapy may also be given to women whose cancer has spread to other parts of the body. Its used in this situation to try to shrink and control the cancer and relieve symptoms, to prolong a good quality of life. In some women the chemotherapy will achieve this. Unfortunately for others the chemotherapy will not shrink the cancer, and in this situation the treatment will be stopped to avoid the side effects it may cause. Its helpful to discuss the pros and cons of chemotherapy in your particular situation with your cancer specialist.

Side effects Back to top

Chemotherapy can cause side effects, which may be slightly worse when its given alongside radiotherapy. Weve listed some of the side effects you may experience.
Lowered resistance to infection (neutropenia)

Chemotherapy can temporarily reduce the production of white blood cells in your bone marrow, making you more prone to infection. This effect can begin about seven days after treatment has been given, and your resistance to infection usually reaches its lowest point about 10-14 days after chemotherapy. Your white blood cells will then increase steadily and will usually return to normal before your next cycle of chemotherapy is due. You should contact your doctor or the hospital straight away if:

your temperature goes above 38C (100.4F) you suddenly feel unwell, even with a normal temperature.

You will have a blood test before having more chemotherapy to make sure that your white blood cells have recovered.Occasionally it may be necessary to delay your treatment if your blood count is still low.

Tips for avoiding infection

Watch our slideshow for advice about how to avoid infection when you have reduced immunity.
Anaemia

If the level of red blood cells in your blood is low, you may feel tired and breathless. This is called anaemia. Anaemia can be treated by having a blood transfusion.
Bruising and bleeding

The chemotherapy can reduce the production of platelets, which help the blood to clot. Having low numbers of platelets increases your chance of bleeding, and this can affect people in different ways. Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, bleeding gums, blood in your urine or stools, blood spots or rashes on the skin. You may need to have a platelet transfusion.
Nausea and vomitting

Some chemotherapy drugs can make you feel sick (nauseated) or be sick (vomit). Your cancer specialist can prescribe effective anti-sickness (anti-emetic) drugs to prevent or greatly reduce this. If the sickness is not controlled, or continues, let your doctor know. They can prescribe other anti-sickness drugs that may be more effective.
Tiredness (fatigue)

Chemotherapy affects people in different ways. Some people find theyre able to lead a fairly normal life during their treatment, but many find they become very tired and have to take things much more slowly. Try to pace yourself by balancing periods of rest with some gentle exercise, such as short walks.
Effects on the kidneys

Some of the chemotherapy drugs used to treat cancer of the cervix may affect the kidneys. Usually this doesnt cause any symptoms, but sometimes the effect can be severe and the kidneys can be permanently damaged unless the treatment is stopped. For this reason your kidney function will be checked by a blood test before each treatment. You may be asked to drink plenty of fluids, and to measure how much liquid you drink and the amount of urine you pass.

Sore mouth

Chemotherapy drugs can sometimes make your mouth sore and cause small mouth ulcers. Some people find that sucking on ice may be soothing. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as they can prescribe mouthwashes and medicine to prevent or clear mouth infections.
Loss of appetite

Some people lose their appetite while theyre having chemotherapy. This can be mild and may only last a few days. If it doesnt improve you can ask to see a dietitian or specialist nurse at your hospital. They can give you advice on improving your appetite and keeping to a healthy weight.
Numbness or tingling in hands or feet

This is due to the effect of some chemotherapy drugs on your nerves and is known as peripheral neuropathy. Tell your doctor if you notice this symptom, as it may be controlled by slightly lowering the dose of the chemotherapy drug. The problem usually improves slowly over a few months after treatment is over, but for some people it can persist. Talk to your doctor if this happens.
Hair loss

Some chemotherapy drugs can cause temporary hair loss. Your doctor or nurse will be able to tell you if youre likely to experience this. There are many ways of covering up hair loss, including wigs, hats and scarves. If you are an inpatient when you have your treatment, or if youre on income support, you can get a free wig from the NHS. If you do lose your hair, it should start to grow back within 3-6 months of finishing treatment. Although they may be difficult to cope with at times, most of these side effects will disappear once your treatment is over.
Fertility

Chemotherapy can affect your ability to become pregnant after treatment. Its important to discuss any concerns you have about this with your hospital team before your treatment starts.
Contraception

Its not advisable to become pregnant while having chemotherapy, as the drugs may harm the developing baby. For this reason, your doctor will advise you to use a reliable method of

contraception (usually a barrier method, such as condoms) throughout your treatment and for a few months afterwards. You can discuss this with your doctor or nurse. Condoms should be used if you have sex within the first 48 hours after chemotherapy. This is to protect your partner from any of the drug that may be present in the vaginal fluid

After treatment for cervical cancer

After your treatment has finished you will need to have regular check-ups. These will often go on for several years and may include blood tests, x-rays or scans.
On this page

What if the cancer comes back? What you can do Lifestyle changes - making positive decisions Emotional support

If you have any problems or ongoing side effects from the treatment, or notice any new symptoms between your check-ups, let your doctor or specialist nurse know as soon as possible. Many women who are treated for early-stage cervical cancer will be completely cured of their cancer and their cancer wont come back.

Watch Nicola's story

Nicola shares her experience of living with and after cervical cancer.

What if the cancer comes back? Back to top

The first couple of times I went back I was quite anxious - being in the same place, it just brings back all the memories of being there and how scared you were, and youre quite relieved when you go home. The more time goes on it becomes better, much better.

If the cancer does come back, you will be given further treatment. The treatment you have will depend on where the cancer is and which treatments youve had before. Treatment may

include surgery, chemotherapy or radiotherapy, and these may be given alone or in combination. Very occasionally, if the cancer comes back just in the pelvic area, it may be possible to have an operation called a pelvic exenteration. This is a major operation and involves removing some or all of the organs in the pelvis, including the womb, cervix, vagina, fallopian tubes, ovaries, bladder and the lower end of the large bowel (rectum). Its only suitable for a small number of women, and various investigations and scans will be needed to see if its possible. If a pelvic exenteration is suitable for you, your hospital consultant will give you more detailed information about this operation and what to expect. If the cancer has spread to other parts of the body (such as the lungs, liver or bone), then chemotherapy is usually given.

What you can do Back to top

After treatment youll probably be keen to get back to doing the things you did before your cancer diagnosis. But you may still be coping with side effects of treatment, such as tiredness, and also with some difficult emotions. Recovery takes time, so try not to be hard on yourself. Its not unusual to feel anxious and even a bit isolated at this time. Women often worry about the cancer coming back, and that any new symptom is a sign that it has returned. If you have any concerns or questions its important to talk these over with your hospital doctor, specialist nurse or GP. They can tell you if theres anything you should or shouldnt be doing, and how to make the most of your health.

Lifestyle changes - making positive decisions Back to top

When youve had time to recover from your treatment you may want to think about making changes to your lifestyle and find out more about healthy living. Perhaps you already followed a healthy lifestyle before your cancer, but you may now want to be more focused on making the most of your health. There are things you can do to help your body recover. These can also help improve your sense of wellbeing and lower your risk of getting other illnesses and some cancers.
Eating well and keeping to a healthy weight

Eat plenty of fresh fruit and vegetables (at least five portions a day) and eat more high-fibre foods. Cut down on red meat, animal fats and salted, pickled and smoked foods.
Regular exercise

Regular exercise can be an important part of your recovery after treatment. It can improve your sense of wellbeing and build up your energy levels. It also reduces the risk of heart disease, stroke, diabetes and bone thinning (osteoporosis). Talk to your cancer specialist or GP before you start. Start slowly and increase your activity over time.

Stopping smoking

If you're a smoker, speak to your doctor or call a stop smoking helpline for further advice and to find out where your local stop smoking service is.
Drinking sensibly

Alcohol has been linked with an increased risk of developing some types of cancer. So try to stick to sensible drinking guidelines, which recommend that women drink less than two units a day and have at least a couple of alcohol-free days each week.

Emotional support Back to top

Its common to have different and sometimes difficult feelings after cancer treatment. But as you recover and get back to your everyday life, these usually become easier to deal with. The type of treatment youve had can have an effect on how you feel. Some women may experience ongoing side effects, which can be difficult to cope with emotionally. Talking to family and friends about how youre feeling often helps. Ask your doctor or nurse for advice and support. Some women find the impact of the cancer leaves them feeling depressed, helpless or anxious. Let your doctor or nurse know how youre feeling, as theres specialist help available to help you cope with these feelings. Your hospital consultant or GP can refer you to a psychologist or counsellor who specialises in the emotional problems of people with cancer. Our cancer support specialists can tell you more about counselling and let you know about services in your area.
Support groups

Self-help or support groups offer a chance to talk to other women who may be in a similar situation and facing the same challenges as you. Joining a group can be helpful if you live alone or dont feel able to talk about your feelings with people you know. Not everyone finds talking in a group easy, so it might not be for you. Try going along to see what the group is like before you join.
Online support

Many people get support through the internet. There are online support groups, social networking sites, forums, chat rooms and blogs for people affected by cancer. You can use these to share your experience and to ask questions, get and give advice based on your cancer experience. Our online community is a social networking site where you can talk to people in our chat rooms, blog your journey, make friends and join support grou

Menopausal symptoms and fertility

The treatments for cervical cancer may cause menopausal symptoms and affect your fertility. There are different treatment options for coping with these effects.
On this page

Menopausal symptoms Fertility

Menopausal symptoms Back to top

If youve had a hysterectomy and your ovaries have been removed, or if youve had radiotherapy to the pelvis, you will go through the menopause if you havent done so already. Some types of chemotherapy can also bring on an early menopause. Menopausal symptoms can include:

hot flushes dry skin dryness of the vagina feeling low or anxious being less interested in sex.

Many of these effects can be eased by hormone creams, skin patches or tablets, which can all be prescribed by your doctor. These replace the hormones that are normally produced by the ovaries. However, these hormone replacement therapies may not be suitable for all women. Your doctor will let you know if they are suitable for you. If dryness of the vagina is a problem, your doctor can prescribe creams or you can buy lubricating gels such as Sylk or Astroglide from the chemist. You can also buy organic lubricants online, such as Yes. You or your partner can apply them directly to the penis or vagina during sex. An organisation called the Daisy Network supports women who have an early menopause. You may find it helpful to contact them if you feel you need a bit more support.

Fertility Back to top

Pelvic radiotherapy or surgical removal of your womb or ovaries will mean you are no longer able to have children. Some chemotherapy drugs may also affect your fertility. This can feel devastating. Infertility is very hard to come to terms with, especially if you were planning to start a family in the future, or to have more children to complete your family. The sense of loss can be very painful and distressing for people of all ages. Sometimes it can feel as though you have actually lost a part of yourself. You may also feel less feminine because you cant have children.

Its important to discuss any concerns you have about your fertility with your healthcare team before treatment starts. They can discuss any options you may have for preserving your fertility. For example, you may be able to store embryos (fertilised eggs), or have your eggs frozen and stored for future use. This would have to happen before treatment starts. Ovarian tissue that contains eggs can also be removed for future use, but this is still a very experimental technique. If you would like to have fertility treatment, your hospital team will refer you to a fertility specialist. Embryo storage may be available on the NHS, but you often have to pay privately for other treatments. People react differently to the risk of infertility. Some women may come to terms with it more quickly and feel that dealing with the cancer is more important. Others may accept the news calmly when they start treatment, and find that they dont feel the full impact until the treatment is over and they are sorting out their lives again. There is no right or wrong way to react. If you have a partner, its important for them to be involved in any discussions about fertility and future plans. You may both need to speak to a professional counsellor or therapist specialising in fertility problems. They can help you come to terms with your situation. Your doctor may be able to refer you to a specialist. Our cancer support specialists can discuss any problems you may have and they can also help you find a counsellor who can offer you help and advice.

How treatment for cervical cancer may affect your sex life
The treatments for cervical cancer may affect your sex life, but many of these effects can be prevented or treated.
On this page

Menopausal symptoms Vaginal care Sex Fertility Emotional effects

The treatments for cervical cancer may affect your sex life, but many of these effects can be prevented or treated. Its important to discuss any concerns or problems with your doctor or nurse. Its natural for you to feel embarrassed, but they are used to talking about these issues and can give you advice and support. Effects of treatment may include:

An early menopause Narrowing of the vagina, which can make sex uncomfortable Feelings of anxiety or nervousness about having sex again

Unfortunately, some treatments for cervical cancer also will stop you from being able to have children. This can feel devastating, even if you were not planning to have children. Talking to a professional counsellor or therapist can help you come to terms with your grief. Your doctor can also discuss options you may have such as storing embryos (fertilised eggs) before treatment begins.

Menopausal symptoms Back to top

If you have had a hysterectomy and your ovaries have been removed, or if youve had radiotherapy to the pelvis, you will go through the menopause (if you havent done so already). Menopausal symptoms can include:

hot flushes dry skin dryness of the vagina feeling low or anxious being less interested in sex.

Many of these effects can be eased by hormone creams, skin patches or tablets, prescribed by your doctor. These replace the hormones that are normally produced by the ovaries.

If dryness of the vagina is a problem, your doctor can prescribe creams or you can buy lubricating gels such as KY Jelly, Sylk or Astroglide from the chemist. You or your partner can apply them directly to the penis or vagina during sex.

Vaginal care Back to top

Radiotherapy to the pelvis can make the vagina become narrower and this can make sex difficult or uncomfortable. The key to overcoming this problem is to keep the muscles in the vagina as supple as possible. Hormone creams applied to the vagina can help, and are available on prescription from your doctor. Using vaginal dilators or having regular penetrative sex are often the best ways to keep the vagina supple. The nurses or your doctor can give you a set of dilators, show you how to use them and answer any questions. They are used to discussing these issues, so you dont need to feel embarrassed. Radiotherapy can cause small fragile blood vessels to develop in the vagina, which can lead to slight vaginal bleeding, particularly after sex. Let your doctor or nurse know if this happens so that they can check that everything is okay.

Sex Back to top

Many women feel nervous about having sex soon after treatment for cancer, but its perfectly safe. Sex wont make the cancer come back and your partner cant catch cancer from you. Women often find that they need to take more time over sex to help the vagina relax. It may also be easier if your partner is gentle at first so that the vagina can stretch slowly. Regular

gentle sex will help the vagina become more supple again and you should be able to go back to your usual sex life a few weeks after the radiotherapy. Women who have had surgery will need to wait longer, usually at least six weeks after their operation, before having sex to allow the body to heal properly. If sex is difficult, you and your partner might find it helps to discuss things with one of your treatment team. Although it might feel embarrassing at first, it can really help to talk things through. Your nurse or doctor will have experience in this area and can advise you about what might help. You also might find it helpful to read our information on sexuality and cancer , which includes suggestions for coping with sexual problems.

Fertility Back to top

Pelvic radiotherapy will stop you from being able to have children. This can feel devastating. Infertility is very hard to come to terms with, especially if you were planning to have children in the future or to have more children to complete your family. The sense of loss can be very painful and distressing for people of all ages. Sometimes it can feel as though you have actually lost a part of yourself. You may feel less feminine because you can't have children. Its important to discuss any concerns you have about your fertility with your healthcare team before treatment starts. They can discuss any options you may have for preserving your fertility. For example, you may be able to store embryos (fertilised eggs), or have your eggs frozen and stored for future use. This must happen before treatment starts. Ovarian tissue which contains eggs can be removed for future use, but this is still a very experimental technique. Embryo storage may be available on the NHS, but you often have to pay privately for other treatments. Sometimes, its possible to surgically move the ovaries before radiotherapy treatment (ovarian transposition), with the aim of preserving fertility. Our information on cancer and fertility in women discusses the options for having a baby (such as adoption, surrogacy or egg storage) if treatment has affected your fertility.

Emotional effects Back to top

People react differently to the risk of infertility. Some women may come to terms with it more quickly and feel that dealing with the cancer is more important. Others may find that they accept the news calmly when they start treatment, and find that they don't feel the full impact until the treatment is over and they are sorting out their lives again. There is no right or wrong way to react. Your partner will also need special consideration in any discussions about fertility and future plans. You may both need to speak to a professional counsellor or therapist specialising in fertility problems. They can help you to come to terms with your situation.

Your doctor may be able to refer you to a specialist. Our cancer support specialists can discuss any problems you may have and they can also help you to find a counsellor who can offer you help and advice.

Living with and after cancer

Cancer can affect many areas of your life such as your finances, work, your emotions and relationships. Find information and advice about what the effects might be, how to deal with them and how we can help.

Financial support
Find practical advice on the possible financial impact of a cancer diagnosis, including what benefits you might be entitled to.

Practical issues
Information on dealing with day-to-day problems, including work, travel, and travel insurance.

Emotional effects
Information on the emotions you might experience as a result of your cancer diagnosis, ways that you might manage them and other sources of support.

Relationships and communication

Advice on how to talk to other people, talking to children, relationships and sexuality.

How we can help

Find out about the ways in which Macmillan can offer you information and support.

Get involved
You can help other people affected by cancer. Campaign for a better deal, give your time, share your experiences or make a donation