Oral microbiome and periodontal diseases in oral HPV infection among people living with HIV

摘要 本研究的目的是了解口腔微生物组和牙周疾病在口腔HPV中的作用 艾滋病病毒感染者（PWH）的免疫基础;拟议的研究还将研究 口腔HPV感染以及健康的社会决定因素是否在口腔微生物组和口腔HPV中发挥作用 感染威尔斯亲王医院。HPV感染已被确定为口咽癌的致癌物质， 在PWH中，口腔HPV感染率，沿着 口咽癌的发病率明显高于一般人群。然而，病因学和 PWH口腔HPV感染的病理生理学没有很好的记录。长期以来，口腔微生物群的作用 在许多口腔感染和疾病的病因学中被认识到。持续的免疫激活和 HIV感染和治疗可能导致炎症和口腔粘膜上皮紧密连接受损 口腔微生物生态失调，导致口腔HPV感染。然而，目前有关该协会的证据表明， 口腔微生物组和口腔HPV感染之间的关系在PWH中缺乏。此外，作为一种多微生物 牙周病是另一种主要的炎症来源，在PWH中最常见 面对ART，可能会促进口腔HPV感染。牙周病的危害有哪些？ 口腔HPV感染和持久性的研究很少，特别是在口腔微生物组的背景下。 此外，口腔微生物组是炎症和免疫调节的关键介质，这两个主要的炎症和免疫调节是由细菌引起的。 口腔HPV感染的原因尽管如此，口腔粘膜对HPV感染的炎症和免疫反应 更少被理解。因此，我们建议对500名PWH进行纵向队列研究，以检查 口腔微生物组、牙周病和口腔HPV感染之间的关联。参与者将被跟踪 最多两年，每六个月进行一次口腔HPV检测和牙周状况检查， 微生物组评估。我们还将每年检查口腔免疫和炎症反应， 研究与口腔微生物组和口腔HPV感染相关的口腔免疫学特征的变化。 此外，我们的合格患者中共有86%是非洲裔美国人，其中52%低于联邦 贫困水平，这表明在接受医疗保健服务的困难和研究社会的重要性， 威尔斯亲王医院的健康决定因素。因此，我们还将探讨健康的社会决定因素的影响， 作为邻近条件，对口腔微生物组和口腔HPV感染的影响。调查结果将提供所需的 关于口腔微生物组和牙周病是否以及如何在口腔HPV中发挥关键作用的证据 威尔斯亲王医院感染个案。确定的口腔微生物群将有助于制定有针对性的干预措施 以减少口腔HPV感染，从而降低PWH中HPV相关HNC的发病率。 解决健康的关键社会决定因素将为以下方面提供宝贵的执行建议： 减少健康差距，改善威尔斯亲王医院与健康相关的成果。

Abstract The goal of this study is to understand the role of the oral microbiome and periodontal diseases in oral HPV infection among people with HIV (PWH); the proposed study will also examine immunological underpinnings of oral HPV infection and whether social determinants of health play a role in the oral microbiome and oral HPV infections for PWH. HPV infection has been identified as a carcinogen for oropharyngeal cancer, the most common HPV-associated cancer in the U.S. Among PWH, rates of oral HPV infection, along with oropharyngeal cancer, are significantly higher than in the general population. Yet, the etiology and pathophysiology of oral HPV infection in PWH are not well-documented. The role of oral microbiota has long been recognized in the etiology of many oral infections and diseases. Persistent immune activation and inflammation and impaired oral mucosa epithelial tight junctions from HIV infection and treatment could result in oral microbial dysbiosis, leading to oral HPV infection. However, current evidence on the association between the oral microbiome and oral HPV infection is lacking among PWH. Additionally, as a polymicrobial condition and another primary inflammatory resource, periodontal diseases are most commonly seen in PWH in the face of ART and may facilitate oral HPV infection. Research evaluating the role of periodontal diseases on oral HPV acquisition and persistence is sparse, particularly in the context of the oral microbiome. Furthermore, the oral microbiome is a crucial mediator of inflammation and immune regulation, two major contributors to oral HPV infection. Still, oral mucosa's inflammatory and immune responses to HPV infection are less understood. Therefore, we propose a longitudinal, cohort study of 500 PWH to examine the association among oral microbiome, periodontal diseases, and oral HPV infection. Participants will be followed up to two years with every six months for oral HPV testing and periodontal status and every year for oral microbiome assessments. We will also examine the oral immune and inflammatory responses yearly and investigate the alterations in oral immunological profiling related to oral microbiome and oral HPV infection. Moreover, a total of 86% of our eligible patients are African American, and 52% of them are below the federal poverty level, suggesting the difficulties in receiving health care services and the importance of studying social determinants of health for PWH. Thus, we will also explore the impact of social determinants of health, such as neighborhood conditions, on oral microbiome and oral HPV infection. Findings will provide needed evidence on whether and how the oral microbiome and periodontal disease play a crucial role in oral HPV infection among PWH. The identified oral microbiota will be instrumental in developing targeted interventions to reduce oral HPV infection and subsequently lower HPV-associated HNC incidences among PWH. Addressing critical social determinants of health will provide invaluable implementation recommendations to reduce health disparities and improve health-related outcomes for PWH.