Oral HPV Infection in HIV-Infected Men and Women

描述(申请人提供)：人乳头瘤病毒在口腔癌的一个不同亚型的发展中起病因学作用，口腔癌主要发生在扁桃体。艾滋病毒感染者患扁桃体癌的风险增加。因此，口腔HPV感染是一个新的公共卫生问题。这项建议的目的是进行一项全面的分子流行病学研究，以确定HIV感染者中口腔人乳头瘤病毒(HPV)感染的流行率、危险因素、传播机制和自然病史，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%。HPV和HIV同时感染可能是导致这一原因不明的增加的原因之一。初步数据表明，在艾滋病毒感染者中，高危HPV感染口腔和扁桃体的几率显著增加，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。一项前瞻性队列研究，对800名感染HIV的男女进行为期36个月的半年随访，以实现以下特定目标：(I)确定口腔粘膜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感染相关的具体性行为；(Iii)评估高危HPV(存在HPV基因组DNA、病毒载量、整合)与扁桃体异常增生及其他口腔粘膜异常的关系，及(Iv)确定吸烟、免疫抑制及HPV类型(低危与高危)是否影响口腔HPV感染的发生率及/或持久性。这项建议有可能为今后的HPV-HNSCC初级预防和早期检测工作提供重要的信息。

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.