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

HIV 感染者口腔 HPV 感染的口腔微生物组和牙周病

基本信息

批准号：
10680541
负责人：
LISA C. FLOWERS
金额：
$ 78.33万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-11 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10680541
关键词：
Address Affect African American Age Atlases Attitude Behavior Disorders Biological Markers Carcinogens Carcinoma Caring Cells Cohort Studies Communities Complex Eligibility Determination Environment Epithelium Etiology Flow Cytometry Functional disorder General Population Goals HIV HIV Infections HIV diagnosis Head and Neck Cancer Health Human Human Papilloma Virus-Related Malignant Neoplasm Human Papillomavirus Human papilloma virus infection Immune Immune response Immunologics Impairment Incidence Inflammation Inflammation Mediators Inflammatory Inflammatory Response Intervention Lead Link Malignant Neoplasms Mediating Metagenomics Mouth Diseases Mucosal Immunity Neighborhoods Oral Oral Examination Oral mucous membrane structure Outcome Participant Pathogenicity Pathologic Pathway interactions Patients Penetration Periodontal Diseases Persons Play Population Predisposition Prevalence Prognosis Recommendation Recurrence Reduce health disparities Research Resources Role Secondary to Solid Neoplasm Survival Rate Testing Tight Junctions Tissues Virus Virus Diseases antiretroviral therapy cancer therapy cancer type dysbiosis federal poverty level follow-up head and neck cancer prevention health care service high dimensionality immune activation immunoregulation improved insight malignant oropharynx neoplasm microbial microbiome microorganism new therapeutic target novel sequencing technology oral HPV oral HPV infection oral HPV-positive head and neck cancers oral cavity epithelium oral infection oral microbial community oral microbiome prevent reconstruction recruit social determinants social health determinants transcriptome sequencing treatment comparison virus related cancer

项目摘要

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.

抽象的这项研究的目的是了解口腔微生物组和牙周疾病在口腔HPV中的作用艾滋病毒（PWH）的感染；拟议的研究还将检查口服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服HPV中起作用 PWH的感染。 HPV感染已被确定为口咽癌的致癌物，最多在美国，PWH，口服HPV感染率的美国常见HPV相关癌症以及口咽癌明显高于普通人群。然而，病因和 PWH中口服HPV感染的病理生理并未得到充分证明。口服微生物群的作用很长在许多口腔感染和疾病的病因学中得到认可。持续的免疫激活和 HIV感染和治疗的炎症和口服粘膜上皮紧密连接处可能导致在口腔微生物营养不良中，导致口服HPV感染。但是，目前有关协会的证据 PWH之间缺乏口服微生物组和口服HPV感染之间。另外，作为多数菌状况和另一种主要炎症资源，牙周疾病最常见于PWH 面对艺术，可能会促进口服HPV感染。研究评估牙周疾病作用的研究关于口服HPV的采集和持久性很少，尤其是在口服微生物组的背景下。此外，口服微生物组是炎症和免疫调节的关键介质，两个主要的口服HPV感染的贡献者。尽管如此，口服粘膜对HPV感染的炎症和免疫反应不了解。因此，我们提出了一项500 PWH的纵向队列研究，以检查口服微生物组，牙周疾病和口服HPV感染之间的关联。参与者将遵循每六个月进行口服HPV测试和牙周状态，每年每年一次，每年都有每年的口服微生物组评估。我们还将每年检查口腔免疫和炎症反应研究与口服微生物组和口服HPV感染有关的口服免疫学分析的改变。此外，我们合格的患者中总共有86％是非裔美国人，其中52％的患者低于联邦贫困水平，表明接受医疗服务的困难以及学习社会的重要性 PWH的健康决定因素。因此，我们还将探讨社会决定因素的影响，作为邻里条件，口服微生物组和口服HPV感染。调查结果将提供所需的关于口服微生物组和牙周疾病在口服HPV中的重要作用的证据 PWH中的感染。确定的口腔微生物群将有助于制定目标干预措施为了减少口服HPV感染，并随后降低了PWH中与HPV相关的HNC发病率。解决关键的卫生社会决定因素将为减少健康差异并改善与健康相关的PWH结果。