Mechanisms of disparities in the natural history of oral and oropharyngeal HPV infection among persons living with HIV: the CAMPO oral cohort study

摘要 口咽癌（OPC）在美国和全球许多地区正在增加。有 美国（US）、波多黎各（PR）和 墨西哥（MX）（分别为每10万人2.4、1.9和0.23）。人乳头瘤病毒（HPV）占 70%的OPC和人类免疫缺陷病毒（PLWH）感染者的风险高出2-3倍。 流行的口腔HPV感染和2-6倍的OPC风险比HIV未感染的个体。虽然研究 免疫抑制的严重程度（CD 4/CD 8比值）与口腔HPV感染的患病率较高相关， PLWH中的过度风险表明其他因素可能促进HPV传播和持续， 导致HPV特异性免疫缺陷和随后的癌症。尽管如此， PLWH中口腔HPV的清除率研究不足。我们的长期目标是研究生物学， 临床和社会文化因素导致的差异，种族差异和OPC的风险增加， 西班牙裔PLWH; OPC预防工作的基本信息。虽然西班牙裔PLWH的风险增加 口腔HPV感染和OPC，西班牙裔人群在遗传背景，地理位置，饮食， 生活方式和其他社会文化行为。使用加利福尼亚-MX-PR（CAMPO）的基础设施 联盟临床试验计划”（U 54 CA 242646），我们将进行多中心队列研究，以实现我们的 目的是了解生物学、临床和社会文化因素的相互作用， 在HIV感染的情况下，口腔HPV感染的发生率和持续性更高。具体目标是：（1） 评估口咽部HPV感染的基线患病率、发病率、清除率和持续率 在墨西哥、PR和San弗朗西斯科（美国）的西班牙裔PLWH中;（2）确定生物因素的影响 (i.e.遗传祖先，口腔微生物群，和HPV甲基化）对口腔HPV感染获得，持续， （3）评估临床（即艾滋病毒感染者的年数、抗逆转录病毒治疗的使用、口服 卫生，牙周炎，肛门生殖器HPV感染，免疫功能障碍）和社会文化（即吸烟，饮食， 性行为、社会经济地位）因素对口腔HPV感染获得、持续和清除的影响 在PLWH中。我们将在MX、PR和弗朗西斯科招募600名西班牙裔PLWH（每个研究中心200名）。 这些个体将每4个月完成一次基线访视和5次额外的随访访视： 随访期20个月。数据收集程序将包括牙周病的口腔评估 评估，用于类型特异性HPV测定的漱口水样本，用于口腔微生物组的唾液样本， HPV甲基化分析，以及用于CD 4/CD 8和血统评估的血液样品。基线和随访 调查还将提供有关社会文化协变量的信息。考虑到HPV的相关性 感染和持续性对OPC风险的影响，我们的研究结果将告知OPC差异的潜在机制 西班牙裔人群的风险。

ABSTRACT Oropharyngeal cancers (OPC) are increasing in the United States and in many regions globally. There are marked differences in the incidence rates of OPC among the United States (US), Puerto Rico (PR), and Mexico (MX) (2.4, 1.9, and 0.23 per 100,000, respectively). Human Papillomavirus (HPV) accounts for over 70% of OPC and people living with Human Immunodeficiency Virus (PLWH) have a 2-3 fold higher risk of prevalent oral HPV infection and 2-6 fold-higher risk of OPC than HIV-uninfected individuals. While studies have associated severity of immunosuppression (CD4/CD8 ratio) with higher prevalence of oral HPV infection, excess risk among PLWH suggests that additional factors may facilitate HPV transmission and persistence, contributing to HPV-specific immune deficiency and subsequent cancer. Nonetheless, the persistence and clearance rates of oral HPV among PLWH are understudied. Our long-term goal is to investigate biological, clinical, and sociocultural factors contributing to disparities, ethnic differences and increased risk of OPC in Hispanic PLWH; essential information for OPC prevention efforts. While Hispanic PLWH are at increased risk of oral HPV infection and OPC, Hispanic populations differ in genetic background, geographic location, diet, lifestyle and other socio-cultural behaviors. Using the infrastructure of the California-MX-PR (CAMPO) Consortium Clinical Trials Program” (U54CA242646), we will perform a multicenter cohort study to achieve our objective of understanding the interplay of biological, clinical and socio-cultural factors contributing to the higher incidence and persistence of oral HPV infection in the context of HIV infection. Specific aims are: (1) To assess baseline prevalence, incidence, clearance, and persistence rates of oropharyngeal HPV infection among Hispanics PLWH in MX, PR and San Francisco (US); (2) To determine the impact of biological factors (i.e. genetic ancestry, oral microbiota, and HPV methylation) on oral HPV infection acquisition, persistence, and clearance among PLWH and (3) To evaluate the impact of clinical (i.e. years living with HIV, ART use, oral hygiene, periodontitis, anogenital HPV infection, immune dysfunction) and socio-cultural (i.e. smoking, diet, sexual behaviors, socioeconomic status) factors on oral HPV infection acquisition, persistence, and clearance among PLWH. We will recruit 600 Hispanic PLWH in MX, PR, and San Francisco (200 in each study site). These individuals will complete a baseline visit and 5 additional follow-up visits every 4 months: for a complete follow-up period of 20 months. Data collection procedures will include oral evaluation for periodontal disease assessment, mouthwash samples for type-specific HPV determination, saliva samples for oral microbiome and HPV-methylation analysis, and blood samples for CD4/CD8 and ancestry assessment. Baseline and follow-up surveys will also provide information on relevant socio-cultural covariates. Given the relevance of HPV infection and persistence on OPC risk, our study results will inform mechanisms underlying disparities in OPC risk among Hispanic populations.