HPV plays an etiologic role in the development of a distinct subset of oral cancers that arise predominantly from the tonsils. HIV-infected individuals are at increased risk for tonsillar cancer. Oral HPV infection is therefore a newly appreciated public health problem. The objective of this proposal is to perform a comprehensive molecular epidemiologic study to determine the prevalence, risk factors, mechanisms of transmission, and natural history of oral human papillomavirus (HPV) infection in HIV-infected individuals and to identify precursor lesions for HPV-associated head and neck squamous cell carcinomas (HPV associated HNSCC). Tonsillar cancers comprise approximately 15-23% of all oral and oropharyngeal cancers. There was a 2-3% increase in tonsillar cancer incidence per year from 1973-1995 in men in the United States. Concurrent HPV and HIV infection may have contributed to this unexplained increase. Preliminary data suggest that the odds of oral and tonsillar infection by a high-risk HPV type are significantly elevated in HIV infected individuals, and that oral HPV infection is associated with sexual behaviors, severity of immunosuppression and the presence of potentially premalignant oral mucosal lesions. A prospective cohort study of 800 HIV-infected men and women with 36 months of semiannual follow-up is proposed to accomplish the following specific aims: (i) to determine the prevalence and type distribution of oral mucosal HPV infection and to characterize host, environmental (tobacco and alcohol) and biological factors (e.g. CD4 count, HIV viral load) associated with oral HPV infection; (ii) to identify specific sexual practices associated with presence of oral HPV infection after adjustment for confounders; (iii) to evaluate the relationship between high-risk HPVs (presence of HPV genomic DNA, viral load, integration) and tonsillar dysplasia and other oral mucosal abnormalities, and (iv) to determine if tobacco use, immunosuppression, and HPV type (low versus high-risk) affect the incidence and/or persistence of oral HPV infection. This proposal has the potential to yield information important for future efforts at primary prevention and early detection of HPV-HNSCC.
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