Evaluating immunity to oral human papillomavirus to understand the lower oropharyngeal cancer risk among MSM

项目摘要 口腔人乳头瘤病毒（HPV）与60-70%的口咽癌（OPC）有关， 在暴露于HPV之前接种疫苗是高度可预防的。男男性行为者（MSM）艾滋病毒感染者 HPV感染的风险很高，但OPC的风险却很低。据推测，重复 肛管粘膜暴露于HPV会产生保护性抗体反应， 口腔HPV感染和持续存在，导致OPC风险降低。目前尚不清楚是否有特定地点 暴露有助于全身免疫，以及全身免疫是否与不同的 粘膜部位之间HPV DNA的表达。本提案的目的是测试HPV特异性 抗体与口腔和直肠粘膜暴露相关， 通过口腔和直肠暴露，保护口腔免受可检测到的HPV DNA的侵害。我们正在利用归档 样本从620名参与者中收集，这些参与者来自一个良好表征的队列（TRUST/RV 368）， 尼日利亚的MSM和跨性别女性，以解开粘膜部位暴露之间的相互作用， 全身免疫和口腔HPV DNA检测。为实现这一目标，我们致力于实现以下具体目标： 目的1：量化HPV类型特异性免疫与粘膜暴露（阴茎，直肠，口腔和口腔）的关系。 直肠）索引自我报告的性行为;目的2：比较类型特异性 血清抗体与型特异性DNA检测在口腔和肛管。调查结果将产生 关于口腔中的类型特异性免疫的信息，以及它是否对检测 粘膜部位HPV DNA。由于口腔是HPV调节的非特征性部位，我们的研究 是开发控制口腔HPV和预防OPC疗法的关键。

Project Abstract Oral human papillomavirus (HPV) is associated with 60-70% of oropharyngeal cancers (OPC), which are highly preventable with vaccination prior to HPV exposure. Men who have sex with men (MSM) living with HIV are at high risk for HPV, but they have a paradoxically low risk of OPC. It is hypothesized that repeated mucosal exposures to HPV in the anal canal generates protective antibody responses, potentially preventing oral HPV acquisition and persistence, resulting in a lower risk of OPC. It remains unclear whether site-specific exposures contribute to systemic immunity and whether systemic immunity is correlated with differential expression of HPV DNA between mucosal sites. The objective of this proposal is to test whether HPV-specific antibodies are associated with oral and rectal mucosal exposures and whether type-specific immunity induced by oral and rectal exposures protect the oral cavity from detectable HPV DNA. We are leveraging archived samples collected cross-sectionally from 620 participants from a well characterized cohort (TRUST/RV368) of MSM and transgender women in Nigeria to disentangle the interactions between mucosal site exposures, systemic immunity, and oral HPV DNA detection. To achieve this goal, we address the following specific aims: AIM 1: Quantify HPV type-specific immunity in relationship to mucosal exposure (penile, rectal, both oral and rectal) indexed to self-reported sexual behavior; AIM 2: Compare the concordance between type-specific serum antibodies with type-specific DNA detection in the oral cavity and anal canal. Findings will yield information on type-specific immunity in the oral cavity and whether it has a differential effect on detection of HPV DNA by mucosal site. With the oral cavity being an uncharacterized site of HPV modulation, our research is key to the development of therapies that control oral HPV and prevent OPC.