Background

Human papillomaviruses (HPV) are known to cause cancers of the cervix and other anogenital tract sites. Molecular biology has provided some evidence as to the specific mechanisms involved in the HPV-related carcinogenesis. Epidemiologic and molecular biology studies have also suggested that HPV infection may be associated with cancers of the head and neck.



Methods

This review summarizes the biology of HPV and its potential etiologic role in head and neck cancer. Published reports were used to determine the prevalence of HPV in benign, precancerous, and neoplastic lesions of the oral cavity, pharynx, and larynx. The prevalence was also examined by head and neck site, HPV type, and method of HPV detection. In addition, the occurrence of HPV in normal head and neck tissue, epidemiologic factors related to HPV infection, and clinical implications are discussed.



Results

Overall, the frequency of HPV in benign and precancerous lesions ranged from 18.5% to 35.9%, depending upon the detection methodology. Based upon the most sensitive method of detection, polymerase chain reaction (PCR), the overall prevalence of HPV in head and neck tumors was 34.5% (416 of 1205 tumors). The majority of HPV-positive tumors contained the “high risk” HPV types 16 (40.0%) and 18 (11.9%). Among head and neck sites, HPV was most often detected in tumors of the oral cavity (59%), followed by the pharynx (43%), and larynx (33%). The frequency of HPV positivity in oral samples from healthy individuals ranged from 1% to 60%. A limited number of descriptive and analytic epidemiologic studies have indicated that age (<60 years) and sex (male) were associated with the presence of HPV in the tumor, whereas tobacco and alcohol use were not. The relationship between HPV and survival is unclear, with few comprehensive studies currently available.



Conclusions

The prevalence of HPV, particularly the high-risk types, suggests a potential etiologic role for the virus in head and neck cancer. Molecular biology has provided important data on the interaction of the HPV oncoproteins with genes important in cell cycle control. Nonetheless, more basic research is needed to describe the physical state of the virus in a variety of cell types and the interaction with other genes. In addition, epidemiologic research is required to further understand the association between HPV and demographic and other risk factors as well as possible routes of transmission. Finally, much work is warranted to provide a definitive assessment of the prognostic significance of HPV in head and neck cancer. © 1998 John Wiley & Sons, Inc. Head Neck 20:250–265, 1998.

Human Papillomavirus and head and neck cancer: Epidemiology and molecular biology

OBJECTIVE: To review the literature on the role of oral sex in the transmission of viral sexually transmitted infections (STIs). METHOD: A Medline search was performed using the keywords oro-genital sex, and those specific to each infection. Further references from each article identified by Medline were also included, as were relevant references from "Current contents". CONCLUSIONS: Oral sex is a common sexual practice among both heterosexual and homosexual couples. The evidence suggests that HIV transmission can take place through oro-genital sex from penis to mouth and vagina to mouth. Case reports describe apparent transmission from mouth to penis although this appears less likely. The risk of oro-genital transmission of HIV is substantially less than from vaginal and anal intercourse. Receptive oro-genital sex carries a small risk of human papillomavirus infection and possibly hepatitis C, while insertive oro-genital contact is an important risk factor for acquisition of HSV 1. Oro-anal transmission can occur with hepatitis A and B. The transmission of other viruses may occur but is unproved. The relative importance of oral sex as a route for the transmission of viruses is likely to increase as other, higher risk sexual practices are avoided for fear of acquiring HIV infection.

https://sti.bmj.com/content/sextrans/74/1/6.full.pdf

Oral sex and the transmission of viral STIs

This review discusses diseases of the lower genital tract in which the presence of human papillomavirus (HPV) DNA is well documented. We discuss epidemiologic, clinical, and experimental data supporting a causative role for HPV in mucosal malignancies, with emphasis on the role of viral and host factors in their pathogenesis. Of special interest is the recently discovered association of cutaneous tumors with HPVs, previously known only for tumors in epidermodysplasia verruciformis (EV). The frequent detection of EV-specific or EV-related HPVs in immunosuppressed persons and in cutaneous tumors in the general population supports the importance of EV as a model of cutaneous oncogenesis. We also discuss recent serologic findings based on enzyme-linked immunosorbent assay results with the use of viruslike particles. This is important both for detection of present or past HPV infection and for epidemiologic and immunologic studies. Novel therapeutic modalities for HPV tumors and prospects for prophylactic and therapeutic vaccination are presented.

Human papillomavirus-associated tumors of the skin and mucosa

In the past 20 years, there has been an increasing interest in human papillomaviruses (HPV) because of their potential role in the pathogenesis of malignant tumors. In 1983, we published the first evidence that HPV might be involved in oral squamous cell carcinomas. The identification of morphological similarities between oral and cervical mucosa lead us to this original proposal. In a recent meta-analysis, HPV was indeed confirmed as an independent risk factor for oral carcinoma. To date, totally more than 100 types of HPV have been identified. As in anogenital cancers, HPV type 16 is the most prevalent type in oral carcinomas. The benign oral lesions, associated with HPV infection, include squamous cell papilloma, condyloma acuminatum, verrucca vulgaris and focal epithelial hyperplasia (FEH). Papillomas and condylomas are mostly caused by HPV type 6 or 11, while oral verrucas are associated with the skin types 2 or 4. A family history of FEH has been suggested. The FEH lesions are caused by HPV types 13 and 32, only detected in oral epithelium. In immunocompromised patients, benign HPV-induced lesions are characterized by atypical morphology and the simultaneous detection of multiple HPV types. Oral benign HPV lesions are mostly asymptomatic, and may persist or regress spontaneously.

Human papillomavirus infections and oral tumors.

More than 65 distinct types of human papillomavirus (HPV) have been identified to date. Several of the HPV types have been proposed as etiologic agents of squamous cell carcinoma. In the oral cavity, HPVs have been found associated with several benign squamous cell proliferations. Evidence from histology and DNA hybridization studies suggests that HPV is also involved in oral carcinogenesis. It is apparent, however, that substantial amount of confusion exists in the diagnosis of oral HPV infections. The keratotic, papillary lesions in the oral cavity are usually small and easily overlooked. The gross appearance of these viral lesions is not distinct enough to be readily diagnosed by the clinicians. Degenerative changes found on oral mucosa frequently simulate koilocytosis. Thus, caution should be exercised to avoid overdiagnosis of HPV infection in the oral cavity. The present review summarizes the current evidence available on HPV infections in general and on oral HPV infections in particular. The diagnostic techniques available as well as the problems encountered in the distinction of these lesions are also discussed in short.

Human papillomavirus (HPV) infections and their associations with oral disease

Warty lesions of the oral cavity were examined for etiologic association with genital tract papillomaviruses HPV-6, HPV-11, and HPV-16. DNAs extracted from ten oral biopsies were screened for HPV genomic sequences by Southern transfer hybridization with 32P-labeled viral DNA probes. Nonstringent hybridization with an HPV-6 probe revealed papillomavirus DNA sequences in four of seven tissues with histologic evidence of papillomatosis, in none of two tissues without histologic evidence of papillomatosis, and in one tissue that was not examined by histology. Stringent hybridization tests with HPV-6 and HPV-16 probes identified the genome in one tissue as being HPV-16, in a second tissue as being HPV-6 subtype a, and in a third tissue as HPV-6 (subtype unidentified); papillomavirus DNA sequences in two tissues are as yet not identified. An additional case of HPV-6 or HPV-11 related oral cavity lesion was diagnosed by in situ hybridization of paraffin sections with a 35S-labeled, mixed HPV-6 + HPV-11 probe. The hybridization in the positive section was extensive and confined to epithelial nuclei. The oral lesions associated with genital tract papillomaviruses were asymptomatic, multiple or single, and were located in different parts of the oral cavity, for example, on the gingivae, on the tongue, on the lip, on the tonsillar pillar, and on the floor of the mouth.

Mark J. Kutcher

Papers

Identification of genital tract papillomaviruses HPV-6 and HPV-16 in warts of the oral cavity.

Blood pressure fluctuations in hypertensive patients during oral surgery