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

HIV 感染者口腔和口咽 HPV 感染自然史差异的机制：CAMPO 口腔队列研究

• 批准号: 10677502
• 负责人: ANA Patricia ORTIZ
• 金额: $ 74.71万
• 依托单位: COMPREHENSIVE CANCER CENTER/ UNIV/PR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-22 至 2024-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10677502
• 关键词: Affect; African; African American; African ancestry; Age; Anogenital Human Papilloma Virus Infection; Bacteria; Behavior; Biological; Biological Factors; Biological Markers; Black Populations; Blood specimen; CD4/CD8 ratio procedure; CD8B1 gene; California; Cervical; Chromosomal Instability; Clinical; Clinical Trials; Cohort Studies; DNA Damage; DNA Integration; Data Collection; Dental Hygiene; Development; Diet; Ethnic Origin; Ethnic group; European; Evaluation; Fibrinogen; Genetic; Genital; Genitalia; Genome; Geographic Locations; Goals; HIV; HIV Infections; HIV antiretroviral; Hemophilus; High Prevalence; Hispanic Populations; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Immune; Immune System Diseases; Immunosuppression; Incidence; Indigenous; Individual; Infection; Inflammatory; Inflammatory Response; Infrastructure; Lactobacillus; Lesion; Life Style; Malignant Neoplasms; Metabolic Clearance Rate; Methylation; Mexico; Minor; Mouthwash; Native American Ancestry; Natural History; Not Hispanic or Latino; Oral; Oral cavity; Oropharyngeal; Pathogenicity; Periodontal Diseases; Periodontitis; Persons; Population Study; Prevalence; Prevention strategy; Procedures; Puerto Rican; Puerto Rico; Research; Risk; Role; Saliva; Sampling; San Francisco; Severities; Sex Behavior; Sex Differences; Site; Smoking; Socioeconomic Status; Surveys; United States; Virus Integration; Visit; Work; antiretroviral therapy; biological sex; cancer prevention; cancer risk; carcinogenicity; dysbiosis; ethnic difference; follow-up; genital microbiome; geographic difference; head and neck cancer patient; high risk; high risk population; immune function; malignant mouth neoplasm; malignant oropharynx neoplasm; men; microbial; mouth squamous cell carcinoma; multi-ethnic; oral HPV; oral HPV infection; oral microbial community; oral microbiome; programs; racial and ethnic; recruit; saliva sample; screening guidelines; social culture; transmission process; tumor

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.

抽象的 在美国和全球许多地区，口咽癌 (OPC) 的发病率正在增加。有 美国 (US)、波多黎各 (PR) 和其他国家之间 OPC 的发病率存在显着差异 墨西哥 (MX)（每 10 万人分别为 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) 感染者患此病的风险高出 2-3 倍 口腔 HPV 感染普遍存在，OPC 风险比未感染 HIV 的人高 2-6 倍。在学习的同时 免疫抑制的严重程度（CD4/CD8 比率）与口腔 HPV 感染患病率较高相关， PLWH 中的过高风险表明其他因素可能会促进 HPV 传播和持续存在， 导致 HPV 特异性免疫缺陷和随后的癌症。尽管如此，坚持和 PLWH 中口腔 HPV 的清除率尚未得到充分研究。我们的长期目标是研究生物学、 导致差异、种族差异和 OPC 风险增加的临床和社会文化因素 西班牙裔艾滋病感染者； OPC 预防工作的重要信息。虽然西班牙裔艾滋病感染者的风险增加 口腔 HPV 感染和 OPC 的影响，西班牙裔人群的遗传背景、地理位置、饮食、 生活方式和其他社会文化行为。使用 California-MX-PR (CAMPO) 的基础设施 联盟临床试验计划”（U54CA242646），我们将进行一项多中心队列研究以实现我们的目标 目的是了解导致疾病发生的生物、临床和社会文化因素之间的相互作用 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、发生率、清除率和持续率 墨西哥、波多黎各和旧金山（美国）的西班牙裔艾滋病感染者； (2)确定生物因素的影响 （即遗传血统、口腔微生物群和 HPV 甲基化）对口腔 HPV 感染获得、持续性、 (3) 评估临床（即感染艾滋病毒的年数、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）影响口腔 HPV 感染获得、持续和清除的因素 感染者之中。我们将在墨西哥、波多黎各和旧金山招募 600 名西班牙裔 PLWH（每个研究点 200 名）。 这些人将每 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、用于特定型 HPV 测定的漱口水样本、用于口腔微生物组的唾液样本以及 HPV 甲基化分析以及用于 CD4/CD8 和血统评估的血液样本。基线和后续行动 调查还将提供相关社会文化协变量的信息。鉴于 HPV 的相关性 感染和持续性 OPC 风险，我们的研究结果将为 OPC 差异背后的机制提供信息 西班牙裔人群中的风险。