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The Merck Manual of Diagnosis and Therapy 17th ed, Beers MH, Berkow R, editors. Portland Merck ! "o.

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CERVICAL CANCER "er)ical cancer is the third *ost co**on gynecologic *alignancy and the eighth *ost co**on *alignancy a*ong wo*en in the +,-. The *ean age for de)eloping cer)ical cancer is a.out /0 yr$ howe)er, it can affect wo*en as young as 10. -.out 12 of all cer)ical cancers occur in pregnant or recently pregnant wo*en 3see Malignancy in "h. 1/14. "er)ical cancer is essentially a se5ually trans*itted disease. Risk is in)ersely related to age at first intercourse and directly related to the lifeti*e nu*.er of se5ual partners. Risk is also increased for se5ual partners of *en whose pre)ious partners had cer)ical cancer. Hu*an papillo*a)irus 3HP64 infection and the de)elop*ent of cer)ical neoplasia are strongly associated. HP6 infection is linked to all grades of cer)ical intraepithelial neoplasia 3"#74 and in)asi)e cer)ical cancer. #nfection with HP6 types 1&, 18, 91, 99, 9/, and 9% increases the risk of neoplasia. Howe)er, other factors appear to contri.ute to *alignant transfor*ation. :or e5a*ple, cigarette s*oking is associated with an increased risk of "#7 and cer)ical cancer. 3,ee also "er)ical "arcino*a in The Merck Manual of ;eriatrics.4 Pathology Precursor cells 3cer)ical dysplasia, "#74 de)elop into in)asi)e cer)ical cancer o)er a nu*.er of years. "#7 grades #, ##, and ### correspond to *ild, *oderate, and se)ere cer)ical dysplasia. "#7 ###, which includes se)ere dysplasia and carcino*a in situ, is unlikely to regress spontaneously and, if untreated, *ay e)entually penetrate the .ase*ent *e*.rane, .eco*ing in)asi)e carcino*a. ,<ua*ous cell carcino*a accounts for 80 to 8/2 of all cer)ical cancers$ adenocarcino*as account for *ost of the rest. ,arco*as and s*all cell neuroendocrine tu*ors are rare. #n)asi)e cer)ical cancer usually spreads .y direct e5tension into surrounding tissues and the )agina or )ia the ly*phatics to the pel)ic and para=aortic ly*ph nodes drained .y the cer)i5. He*atologic spread is possi.le. Symptoms and Signs "#7 is usually asy*pto*atic and disco)ered .ecause of an a.nor*al Pap s*ear. Patients with early= stage cer)ical cancer usually present with irregular )aginal .leeding, which is *ost often postcoital, .ut inter*enstrual .leeding or *eno*etrorrhagia *ay occur. Patients with larger cer)ical cancers or ad)anced= stage disease *ay present with foul=s*elling )aginal discharge, a.nor*al )aginal .leeding, or pel)ic pain. >.structi)e uropathy, .ack pain, and leg swelling are *anifestations of late=stage disease. Diagnosis More than %02 of early asy*pto*atic cases of "#7 can .e detected preclinically .y cytologic e5a*ination of Pap s*ears o.tained directly fro* the cer)i5. Howe)er, the false=negati)e rate is 1/ to '02, depending on the patient population and the la.oratory. -.out /02 of patients with cer)ical cancer ha)e ne)er had a Pap s*ear or ha)e not had one for ? 10 yr. The patients at higher risk for cer)ical neoplasia are the least likely to .e tested regularly. -n a.nor*al Pap s*ear 3ie, suggesting neoplasia, including dysplasia, "#7, carcino*a in situ, *icroin)asi)e carcino*a, or in)asi)e carcino*a4 re<uires further e)aluation .ased on the descripti)e diagnosis of the Pap s*ear and the patient@s risk factors 3see Ta.le 1'1(94. The cellular classification syste* 3# to 64 is no longer used. ,uspicious cer)ical lesions should .e .iopsied directly. #f there is no o.)ious in)asi)e lesion, colposcopy can .e used to identify areas that re<uire .iopsy and to localiAe the lesion. "olposcopy results can .e clinically correlated 3.y assessing characteristic color changes, )ascular patterns, and *argins4 with the results of the Pap s*ear. "olposcopy=directed .iopsy usually pro)ides enough clinical e)idence for an accurate diagnosis. #f colposcopic e)aluation is unsatisfactory or inconclusi)e, a cer)ical coniAation .iopsy is re<uired, perfor*ed )ia a loop electrical e5cision procedure 3BCCP4, laser, or cold knife. 1

#f cer)ical disease is in)asi)e, staging is perfor*ed on the .asis of the physical e5a*ination, with a *etastatic sur)ey including cystoscopy, sig*oidoscopy, #6 pyelography, chest 5=ray, and skeletal 5=rays 3see Ta.le 1'1('4. :or early=stage disease 3#B or less4, chest 5=ray is usually the only adDuncti)e test needed. "T or MR# of the a.do*en and pel)is is optional$ the results cannot .e used to deter*ine the clinical stage. Prognosis and Treatment #n)asi)e s<ua*ous cell carcino*a usually re*ains localiAed or regional for a considera.le ti*e$ distant *etastases occur late. The /=yr sur)i)al rates are 80 to %02 for stage #, /0 to &/2 for stage ##, 1/ to 9/2 for stage ###, and 0 to 1/2 for stage #6. 7early 802 of recurrences *anifest within 1 yr. -d)erse prognostic factors include ly*ph node in)ol)e*ent, large tu*or siAe and )olu*e, deep cer)ical stro*al in)asion, para*etrial in)asion, )ascular space in)asion, and neuroendocrine histology. :or wo*en with prein)asi)e cer)ical disease or *icroin)asi)e s<ua*ous cell carcino*a of the cer)i5, coniAation .iopsy with BCCP, laser, or cold knife or cryotherapy is usually ade<uate treat*ent. +nco**only, a hysterecto*y is re<uired to treat prein)asi)e cer)ical disease. Because the tu*or ad)ances .y direct spread or )ia ly*phatics, treat*ent *ust include the regional nodes. Radiation therapy or surgery *ay .e appropriate. Preser)ing surrounding nor*al tissues is also a goal. Pri*ary surgical treat*ent is reser)ed for patients with li*ited tu*or spread. Patients with *icroin)asi)e disease 3defined as tu*or in)ading no *ore than 9 ** in depth fro* the .ase*ent *e*.rane without )ascular space in)asion and with negati)e *argins on cer)ical coniAation4 *ay .e treated with an e5trafascial hysterecto*y. The risk of recurrence and ly*ph node *etastasis for these patients is E 12. Pel)ic ly*ph node dissection is not indicated. Patients with stage #-1, #B, or ##- disease can .e treated with radical hysterecto*y, including .ilateral pel)ic ly*ph node dissection and re*o)al of all adDacent liga*ents 3cardinal, uterosacral4 and para*etria, or with radiation therapy. The /=yr cure rates for wo*en with stage #B or ##- disease are 8/ to %02 with either therapy. The ad)antages of surgery include a relati)ely short treat*ent ti*e, pro)ision of surgical staging data, preser)ation of o)aries in young wo*en, and a)oidance of )aginal stenosis and of late co*plications of radiation therapy. - *aDor co*plication 3eg, uretero)aginal or )esico)aginal fistula for*ation4 occurs in E 12 of patients. #f e5tracer)ical spread is noted during surgery, postoperati)e radiation *ay pre)ent local recurrence. The ad)antages of radiation therapy are a)oidance of the *or.idity of *aDor surgery, outpatient location, and suita.ility for poor surgical candidates. C5ternal .ea* radiation therapy shrinks the central tu*or and treats the regional ly*ph nodes$ this therapy is followed .y .rachytherapy 3local radioacti)e applications, usually using cesiu*4 to the cer)i5, which destroys the central pri*ary tu*or. MaDor acute co*plications include radiation proctitis and cystitis. Bate co*plications, such as .owel o.struction and recto)aginal and )esico)aginal fistula for*ation, occasionally occur. :or patients with stage ##B, ###, or #6 disease, the treat*ent of choice is radiation therapy. Many ad)anced lesions re<uire large doses. The failure rate for .ulky and ad)anced=stage tu*ors within the pel)is is '02, and the risk of pel)ic and para=aortic ly*ph node *etastasis and of distant *etastasis is su.stantial. +sing che*otherapy as a radiation sensitiAer to control pel)ic disease *ay .e useful. Before radiation therapy, surgical staging can .e perfor*ed to assess the para=aortic ly*ph nodes, and e5tended=field radiation therapy can .e deli)ered to this area if indicated. #f tu*ors are restricted to the pel)is and in)ol)e the rectu* or .ladder, e5enteration 3e5cision of all pel)ic organs4 *ay .e considered. Howe)er, radiation therapy is usually tried first. C5enteration is the treat*ent of choice for recurrent or persistent cancer confined to the central pel)is after con)entional radiation therapy. #t cures up to /02 of patients. Recent refine*ents in this operation include a continent urosto*y, low anterior rectal anasto*osis without colosto*y, o*ental carpet to close the pel)ic floor, )aginal reconstruction with gracilis or rectus a.do*inis *yocutaneous flaps, and i*pro)ed perioperati)e care. Because radiation therapy and surgery are usually successful, che*otherapy is not used as pri*ary treat*ent unless the patient presents with widely *etastatic disease. ,yste*ic che*otherapy is not considered curati)e. Distant *etastases outside the radiation field appear to respond .etter to che*otherapy than does the pre)iously irradiated central pel)ic tu*or. "ytoto5ic drugs produce o.Decti)e, short=li)ed regression in only 1/ to 902 of patients. "isplatin and ifosfa*ide are the *ost acti)e