Oral HPV Research Among Latin Americans Living with HIV (ORAL - H² Study)

摘要 口咽癌(OPC)主要由HPV16和其他致癌类型的HPV引起， 对男性和艾滋病毒携带者(PLWH)的影响不成比例。目前还没有可靠的方法来检测OPC 癌前病变为二级预防。评估9vHPV疫苗预防OPC效果的试验 由我们的团队正在进行：NCI资助的U54赠款，口腔和宫颈癌研究，HPV和HIV在 美洲[ROCCHHA]针对艾滋病毒携带者的201项试验，以及默克V503-049针对未感染艾滋病毒者的试验 男人。虽然接种HPV疫苗是OPC初级预防的一种有前途的方法，但接种疫苗可能不会 提供给最有需要的人，因为大多数国家将男性排除在其国家计划之外，并且可能没有 公共卫生部门的疫苗接种政策。预防OPC和确定PLWH风险最高的其他方法 迫切需要监测，特别是考虑到OPC发病率在 美国和拉丁美洲。为预防策略提供信息，识别可更改的风险因素，并轻松 需要测量的生物标记物来识别那些风险最高的人。人乳头瘤病毒相关OPC的发展是多方面的 阶乘。性行为导致口腔致癌性HPV感染是必要的步骤。不管 解剖部位的感染，只有一部分感染持续并进展为癌症。多重互动 影响病毒持久性的因素。我们是少数几个进行了大量口服HPV Natural的组织之一 历史研究为这部文学做出了贡献。我们和其他研究的结果表明，年龄较大、贫穷 口腔健康，免疫失调，如PLWH，以及DNA甲基化异常影响口腔 HPV持久型。雪上加霜的是，PLWH活得更老了，这导致了终身免疫 功能障碍可能会加速生物衰老，增加获得或重新激活大量 感染，如EB病毒，并最终导致减少致癌病毒控制。社会因素加剧了这一点 由于PLWH对牙科护理和其他服务的利用率较低，导致长时间未治疗的口腔 感染、随后的慢性口腔炎症、牙周病和牙齿脱落，这些因素可能 促进口腔HPV致癌，并已独立地与HPV-OPC风险相关。我们是 作为我们ROCCHHA拨款的一部分，在PLWH中进行两项大型研究，获得临床数据和口腔 在每两年一次的研究访问中为标本漱口，我们将利用这一机会来研究口腔HPV自然历史。的目标是 这一应用是为了确定PLWH中致癌性口腔HPV感染的自然病史。中环 拉丁美洲艾滋病毒携带者口服HPV研究(口服H2)研究的假设是 在PLWH中，高龄生物年龄、牙齿健康和病毒因素与持久口腔有关 致癌的人乳头瘤病毒。我们将评估口腔HPV16和致癌性HPV感染，评估与病毒相关的因素 持久性，并确定预测口腔的生物标志物和行为因素的最佳组合 致癌的HPV持续存在。

ABSTRACT Oropharyngeal cancer (OPC) is predominantly caused by HPV 16 and other oncogenic HPV types and disproportionately impacts men and people living with HIV (PLWH). There is no reliable method to detect OPC pre-cancerous lesions for secondary prevention. Trials assessing efficacy of the 9vHPV vaccine to prevent OPC are ongoing by our team: NCI-funded U54 grant, Research on Oral and Cervical Cancer, HPV and HIV in the Americas [ROCCHHA] Trial 201 among men with HIV, and the Merck v503-049 trial among HIV-uninfected men. While HPV vaccination is a promising approach for the primary prevention of OPC, vaccination may not be available to those in greatest need as most countries exclude males in their national programs and may not have policies for PLWH vaccination. Additional methods to prevent OPC and identify PLWH at highest risk for surveillance are urgently needed, particularly given that OPC incidence rates are significantly increasing in the US and Latin America. To inform prevention strategies, the identification of modifiable risk factors and easily measured biomarkers identifying those at highest risk is needed. Development of HPV-related OPC is multi- factorial. Sexual behavior leading to an oral oncogenic HPV infection is a necessary step. Regardless of anatomic site of infection, only a proportion of infections persist and progress to cancer. Multiple interplaying factors influence viral persistence. We are among the few groups that have conducted large oral HPV natural history studies contributing to this literature. Results from ours and other studies indicate that older age, poor oral health, immune dysregulation, such as occurs among PLWH, and aberrant DNA methylation influence oral HPV persistence. Exacerbating this is the fact that PLWH are living to older ages which results in lifelong immune dysfunction that may accelerate biological aging, increase risk of acquiring or reactivating a multitude of infections such as EBV, and ultimately lead to reduced oncogenic viral control. Social factors compound this scenario as PLWH have lower utilization of dental care and other services resulting in prolonged untreated oral infections, subsequent chronic oral inflammation, periodontal disease, and tooth loss, factors that potentially promote oral HPV carcinogenesis, and have independently been associated with HPV-OPC risk. We are conducting two large studies as part of our ROCCHHA grant among PLWH that obtain clinical data and oral gargle specimens at bi-annual study visits, which we will leverage to study oral HPV natural history. The goal of this application is to define the natural history of oncogenic oral HPV infection among PLWH. The central hypothesis of the Oral HPV Research Among Latin Americans Living with HIV (ORAL H2) Study is that among PLWH advanced biological age, dental health, and viral factors are associated with persistent oral oncogenic HPV. We will estimate oral HPV 16 and oncogenic HPV infection, assess factors associated with viral persistence, and determine the optimal combination of biomarkers and behavioral factors that predict oral oncogenic HPV persistence.