Oral HPV Infection in HIV-Infected Men and Women

描述（由申请人提供）：HPV在主要由扁桃体引起的口腔癌的一个独特子集的发展中起病因学作用。感染艾滋病毒的人患扁桃体癌的风险增加。因此，口腔HPV感染是一个新近受到重视的公共卫生问题。本提案的目的是进行一项全面的分子流行病学研究，以确定hiv感染者口腔人乳头瘤病毒（HPV）感染的患病率、危险因素、传播机制和自然史，并确定HPV相关头颈部鳞状细胞癌（HPV相关HNSCC）的前驱病变。扁桃体癌约占所有口腔癌和口咽癌的15-23%。从1973年到1995年，美国男性扁桃体癌的发病率每年增加2-3%。同时感染HPV和HIV可能是导致这种无法解释的增加的原因。初步数据表明，在HIV感染者中，高危型HPV感染口腔和扁桃体的几率显著升高，并且口腔HPV感染与性行为、免疫抑制的严重程度和潜在的癌前口腔粘膜病变有关。一项针对800名HIV感染者的前瞻性队列研究，每半年随访36个月，以实现以下具体目标：(i)确定口腔黏膜HPV感染的患病率和类型分布，并确定与口腔HPV感染相关的宿主、环境（烟草和酒精）和生物因素（如CD4计数、HIV病毒载量）；（ii）在调整混杂因素后，确定与口腔HPV感染存在相关的特定性行为；（iii）评估高危HPV （HPV基因组DNA的存在、病毒载量、整合）与扁桃体发育不良和其他口腔粘膜异常之间的关系；（iv）确定烟草使用、免疫抑制和HPV类型（低与高风险）是否影响口腔HPV感染的发生率和/或持续性。这一建议有可能为未来HPV-HNSCC的一级预防和早期发现提供重要信息。

DESCRIPTION (provided by applicant): 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.