Oral HPV Infection and Head and Neck Squamous Cell Carcinoma in HIV-infected and HIV-uninfected Individuals
Beachler, Daniel C.
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Background: Oral HPV infection is etiologically associated with a subset of Head and Neck Squamous Cell Carcinomas (HNSCCs). However, the natural history and risk factors of this infection are largely unexplored particularly in high risk groups such as HIV-infected individuals. Objectives: This dissertation aims to examine the natural history and risk factors for oral HPV infection and HPV-related HNSCC in HIV-infected and HIV-uninfected individuals. Methods: We utilized three different longitudinal studies involving HIV-infected individuals. We semi-annually collected oral rinse samples (in the first and second studies) and anal swabs (in the first study) and analyzed them for 37 different HPV DNA types utilizing the Roche Linear array. In the third study, HNSCCs were validated through chart review or through cancer registry-linkage. In each study, we collected information on biologic and behavior risk factors. We analyzed data utilizing 1) Kaplan-Meier survival analysis, 2) Wei-Lin-Weissfeld regression, and 3) Mixed effects Poisson regression. Results: Study 1: Among HIV-infected individuals, the prevalence (84% vs. 28%), incidence (aHR=4.7, 95%CI=3.6-6.2) and persistence (aHR=1.5, 95%CI=1.2-1.9) were all significantly higher for anal versus oral HPV infections, respectively. Study 2: While 28% of HIV-infected and at risk HIV-uninfected participants had at least one type-specific incident oral HPV infection within 24 months, only 7% of incident oral HPV infections were persistently detected for two or more years. Oral sex and immunosuppression were associated with increased risk of oral HPV infection, while male gender, older age, and current cigarette smoking were associated with increased persistence. Study 3: HPV-related HNSCC is three times more common in HIV-infected individuals compared to the general population. HNSCC was associated with reduced CD4 measured prior to cancer diagnosis. Conclusion: Oral HPV infection is regularly detected in HIV-infected individuals, but commonly clears and HPV-related HNSCC is only modestly elevated in HIV-infected individuals compared to the general population. Older age, gender/sexual orientation, cigarette smoking, and oral sexual behaviors all appear to impact the natural history of oral HPV. HIV-related immunosuppression appears to have the strongest impact in the acquisition or re-activation of oral HPV, but may have a modest role throughout the oral carcinogenesis process.