Abstract
Human papillomavirus(HPV) constitutes the majority of newly acquired sexually transmitted infections(STIs)
in United States as per the centers for disease control factsheet 2013. Genital HPV is the most common STI
with incidence of about 5.5 million worldwide, nearly 75% of sexually active men and women have been
exposed to HPV at some point in their lives. Oral Sexual behavior is an important contributor to infection of
HPV in the oral mucosa especially in cases known to practice high risk behavior and initiating the same at
an early age. HPV infection of the oral mucosa currents is believed to affect 150% of the general population,
depending on the method used for diagnosis. The immune system clears most HPV naturally within 2years
(about 90%), but the ones that persist can cause serious diseases. HPV is an essential carcinogen being
implicated increasingly in association with cancers occurring at numerous sites in the body. Though there
does not occur any specific treatment for the HPV infection, the diseases it causes are treatable such as
genital warts, cervical and other cancers.
Indian Journal of Sexually Transmitted Diseases and AIDS 2013; Vol. 34, No. 2 77
Bharti and Marfatia: An update on oral Human papillomavirus
78 Indian Journal of Sexually Transmitted Diseases and AIDS 2013; Vol. 34, No. 2
Bharti and Marfatia: An update on oral human papillomavirus
characterized by little pinkish or whitish nodules, clinically or histologically as any other disease. It is
which proliferate over tongue, lips, palate and floor considered to be premalignant lesion of oral cavity
of mouth which can be sessile or pedunculated. and has a potential of 1662% of getting converted
The surface contour is usually cauliflower like. HPV into oral SCC.[36] Oral leukoplakia is commonly caused
types 6 and 11 have commonly been detected with by HPV types 6, 11 and 16.[37] No consensus as to the
immunohistochemistry and by hybridization with best treatment course and prevention remains the best
7585% positivity.[28,29] approach. Nonsurgical treatment based on topical
bleomycin and systemic retinoids. Invasive treatment
Common warts(Verruca vulgaris) includes cryosurgery, CO2 laser and surgical resection.
Verruca vulgaris is one of the most common They are effective in the short run, nut lesions may
manifestation seen mainly in children can infect oral relapse in the long run.
mucosa.[24] It is usually seen on lips, hard palate,
gingival and dorsal surface of tongue. The most Oral squamous cell carcinoma
common HPV types affecting the musocostrofics(6, In 1976, the first description of relation between
11 and 16) and the cutaneoustrofic(1, 2, 4 and 7) OSCC and HPV was described by Zur Hausen, since
and HPV2 and HPV4 are detected in more than then it has been as an exclusive cause for Cervical
55% of oral lesions.[30] Usually warts are selflimited Carcinoma.[31] HPV was seen in association to 20%
and resolve within 2years. Treatment is sought of OSCC cases as reported in 1983 by Syrjanen.[38]
usually because of esthetic discomfort or to avoid
bite injuries. HNSCC are a major cause of morbidity and mortality
worldwide especially in the Indian subcontinent
with>90% of which are SCC and rank sixth among
Oral lichen planus
all malignancies worldwide.[39]
OLP chronic immunomediated disease with
unknown etiology, which is seen commonly in
More than 90% HNSCC and anogenital cancers are
relation with skin and mucosal lesions associated
caused by HPV16 type. It represents 3% of malignant
with HPV. [31,32] It is commonly seen in age group
transformation, i.e.more than 5,000 diagnosed cases a
of 3060years predominantly in females, though
day and more than 90% of oral cancers. HPV infection
it can also be seen in children and adolescents.
influences the prognosis of the SCC[Table2]. The
The lesions of OLP are generally bilateral and
similarities between the oral and genital injuries along
symmetrical, affects the oral mucosa, gingival, the
with the following factors point toward a role of HPV
dorsum of tongue and lip mucosa. HPV types 11 and infection in oral mucosa, i.e.Affinity to epithelial
16 are commonly found in about 87% of patients. cells, type of genital and oropharyngeal epithelia and
Treatment with corticosteroids reduces the symptoms oncogenic potential of HPV.[40]
but does not cure the condition, treatment with
calcineurin inhibitors, topical retinoids are also used
as additive therapy.[33,34]
Recurrent respiratory papillomatosis
It is characterized by the proliferation of benign
squamous papillomas within the aerodigestive
Oral verrucous carcinoma tract.[4143] In 75% of children with RRP, the diagnosis
A variant of squamous cell carcinoma (SCC), which was made before the childs 50 th birthday and in
is benign with welldistinguished morphology adults in fourth decade. [44] It is mainly caused
and clinical presentation. It is a rare tumor by HPV6 and HPV11, found usually over oral
described by Ackerman in 1948 as a cancer that mucosa, trachea and bronchi and esophagus. In
commonly involves lips, oropharynx and laryngeal 1998, Wanget al. reported this disease presenting
mucosa. It is also known as Achermans tumor, in age<5years it is referred as Juvenile Onset
florid papilomatosis, epithelioma cuniculatum and RRP is thought to be vertically transmitted during
carcinoma cuniculatum[35] and Buschke Loewestein. the childbirth, although transplacental transmission
Commonly caused by HPV types 6, 11, 16 and has also been reported. [45] Treatment modalities
18.[24] The treatment of choice is surgical resection, include cold steel excision, CO2 laser and adjuvant
Radiotherapy with resection, cytostatic drugs like modalities such as interferon, ribavarin, cidofovir,
interferon. Recurrence rate is high when isolated photodynamic therapy, HPV vaccine etc.
surgical resection or radiotherapy is performed.[35]
WHIM syndrome
Oral leukoplakia It is a rare Autosomal Dominant syndrome
MartorellCalatayud A. described oral leukoplakia as characterized by warts, hypogammaglobulinemia,
a white patch or plaque that cannot be characterized infections and retention of mature neutrophils in
Indian Journal of Sexually Transmitted Diseases and AIDS 2013; Vol. 34, No. 2 79
Bharti and Marfatia: An update on oral Human papillomavirus
Table2: Difference between oropharyngeal variety of stem cells and progenitor cells, but its role
cancer HPV+ and HPV is not wellcharacterized.[46]
HPV positives HPV negatives
Age Younger Older RELATION TO HUMAN
individuals (3050) individuals (5070) IMMUNODEFICIENCY VIRUS
Risk factors Oral sex, french kiss, H/O tobacco
high number of sexual and/or alcohol Sikora et al. proved that seropositive individuals
partners consumption show a higher prevalence of oral infection with high
Incidence Increasing Decreasing oncogenic risk HPV, which increase with age, male
Location Base of tongue, Oral mucosa gender and infection by Virion Host Shutoff2
amygdalae
protein.[29]
Field No Yes
cancerization
Histology Poorly Clearly
Seropositive individuals also have a higher risk of
differentiated basaloid differentiated getting oral HPV infection from more than one HPV
Stage of T34, N23 Variable types, further increasing the oncogenic potential
diagnosis of the infection. [21] The risk of infection by high
Biomarkers Overexpressed P16, Loss of P16; P53 oncogenic types of HPV is 13times greater in HIV
inactivation of P16 and and pRb mutation; positive individuals who practiced oral sex with
pRb cyclin D1, EGFR
more than one person during the previous year.[29,47]
and survivine
overexpression
Chromosomal Less frequent Frequent RELATION TO PREGNANCY
mutations
Prognosis Very good, increased Poor
Genital warts in pregnancy flourish well with
sensitivity to increase in size and number, which is believed to
radiotherapy and be due to hormonal influence, increased vascularity
chemotherapy and relative immunedeficiency. Elective caesarean
Distant Rare Frequent is advised in case of genital warts as vertical
metastasis
transmission of HPV DNA from an HPV infected
Second Rare Frequent
primaries
mother to a neonate is increased if the infant is
Five years 6090 2070
delivered through an infected cervix. However the
survival rate % absence of persistent infections infection infants
HPV=Human papillomavirus; EGFR=Epidermal growth factor receptor at 6months after delivery may suggest temporary
inoculation rather than true vertical infection.[48]
Table3: Laboratory investigations
Despite the overwhelming evidence for a sexual
Laboratory investigations for detection of human papilloma
virus transmission of highrisk HPVs, other routes of
Direct method transmission have been proposed. Several studies
Light microscopy: Microscopic cellular features. Low sensibility have explored whether HPVs can be vertically
and does not indicate HPV types transmitted from mother to child by direct contact
Electron microscopy: HPV particles can be identified during labor, or horizontally through manipulation
Drawbacks of the child with infected hands, bathing, towels
HPV types cannot be detected and fomites. 19.7% of the 66 infants born to HPV
Molecular methods positive mothers and 16.9% of the 77 infants
Nonamplified technique born to HPVnegative mothers tested HPVDNA
In situ hybridization positive at some point during followup thus
Southern blot and dot blot Children of mothers who were HPVpositive at the
Amplified technique postpartum visit are nearly 5times more likely to
Target amplification test HPVpositive than children of corresponding
Hybrid captured technology
HPVnegative mothers.[49] The oncogenic HPV types
HPV=Human papillomavirus
16, 18, 31, 33 and 35 are common, whereas HPV
types 6 and 11 are rarely seen. The interaction
the bone marrow(myelokathexis) also associated between oral HPV and Pregnancy is yet to be studied.
with increased susceptibility to HPV infections is
also reported. The occurrence of HPV related SCC
in two sibling with WHIM syndrome was reported
CONCLUSION
by Cipriani etal. Amutation in chemokine receptor Oropharyngeal HPV infection is primarily associated
CXCR4, a 7transmembrane protein expressed in a with sexual activities especially orogenital sex
80 Indian Journal of Sexually Transmitted Diseases and AIDS 2013; Vol. 34, No. 2
Bharti and Marfatia: An update on oral human papillomavirus
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