Evaluating immunity to oral human papillomavirus to understand the lower oropharyngeal cancer risk among MSM

评估对口腔人乳头瘤病毒的免疫力，以了解 MSM 中口咽癌的风险较低

基本信息

批准号：
10491845
负责人：
Rebecca G. Nowak
金额：
$ 19.69万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-21 至 2024-09-21
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491845
关键词：
Accounting Acquired Immunodeficiency Syndrome Address Affect Anal Sex Anal canal Anatomy Antibodies Antibody Response Antibody titer measurement Antigen-Presenting Cells Anus Biological Assay Bisexual Canis familiaris Capsid Country DNA Data Detection Exposure to Future Gays General Population Generations Genotype Goals HIV HPV-High Risk Heterosexuals Human Papilloma Virus Vaccine Human Papillomavirus Human papillomavirus 16 Immune Immune response Immunity Immunoassay Immunoglobulin A Immunoglobulin G Immunologics Incidence Individual Infection Laboratories Lesion Linear Regressions Low Prevalence Lymphoid Measurement Measures Mediating Modeling Mucous Membrane Nigeria Oncogenic Oral Oral Sex Oral cavity Oral mucous membrane structure Papillomavirus Participant Patient Self-Report Persons Plasma Positioning Attribute Proxy Research Risk Serum Sex Behavior Sex Orientation Site Smoking Standardization Swab Testing Vaccination Viral Viral Load result Virus-like particle Work base cancer risk cohort differential expression high risk indexing insight keratinization logarithm malignant oropharynx neoplasm man men men who have sex with men mucosal site oral HPV penis prevent rectal sample archive seropositive sex sexually active therapy development transgender women vaccine acceptance

项目摘要

Project Abstract Oral human papillomavirus (HPV) is associated with 60-70% of oropharyngeal cancers (OPC), which are highly preventable with vaccination prior to HPV exposure. Men who have sex with men (MSM) living with HIV are at high risk for HPV, but they have a paradoxically low risk of OPC. It is hypothesized that repeated mucosal exposures to HPV in the anal canal generates protective antibody responses, potentially preventing oral HPV acquisition and persistence, resulting in a lower risk of OPC. It remains unclear whether site-specific exposures contribute to systemic immunity and whether systemic immunity is correlated with differential expression of HPV DNA between mucosal sites. The objective of this proposal is to test whether HPV-specific antibodies are associated with oral and rectal mucosal exposures and whether type-specific immunity induced by oral and rectal exposures protect the oral cavity from detectable HPV DNA. We are leveraging archived samples collected cross-sectionally from 620 participants from a well characterized cohort (TRUST/RV368) of MSM and transgender women in Nigeria to disentangle the interactions between mucosal site exposures, systemic immunity, and oral HPV DNA detection. To achieve this goal, we address the following specific aims: AIM 1: Quantify HPV type-specific immunity in relationship to mucosal exposure (penile, rectal, both oral and rectal) indexed to self-reported sexual behavior; AIM 2: Compare the concordance between type-specific serum antibodies with type-specific DNA detection in the oral cavity and anal canal. Findings will yield information on type-specific immunity in the oral cavity and whether it has a differential effect on detection of HPV DNA by mucosal site. With the oral cavity being an uncharacterized site of HPV modulation, our research is key to the development of therapies that control oral HPV and prevent OPC.

项目摘要口腔人乳头瘤病毒 (HPV) 与 60-70% 的口咽癌 (OPC) 相关，这些癌症在接触 HPV 之前接种疫苗是可以高度预防的。感染艾滋病毒的男男性接触者 (MSM) HPV 的风险很高，但 OPC 的风险却很低。假设重复肛管中的粘膜暴露于 HPV 会产生保护性抗体反应，可能预防口腔 HPV 获得并持续存在，从而降低 OPC 风险。目前还不清楚是否存在特定地点暴露有助于系统免疫以及系统免疫是否与差异相关粘膜部位之间 HPV DNA 的表达。该提案的目的是测试 HPV 是否具有特异性抗体与口腔和直肠粘膜暴露以及是否诱导类型特异性免疫有关通过口腔和直肠暴露可以保护口腔免受可检测到的 HPV DNA 的影响。我们正在利用存档从 620 名参与者中横断面收集的样本，这些参与者来自一个特征明确的队列 (TRUST/RV368) 尼日利亚的 MSM 和跨性别女性要理清粘膜部位暴露之间的相互作用，全身免疫、口腔HPV DNA检测。为了实现这一目标，我们实现以下具体目标：目标 1：量化与粘膜暴露（阴茎、直肠、口腔和口腔）相关的 HPV 类型特异性免疫力直肠）与自我报告的性行为相关；目标 2：比较特定类型之间的一致性口腔和肛管中具有类型特异性 DNA 检测的血清抗体。调查结果将产生有关口腔中类型特异性免疫的信息以及它是否对检测有不同的影响粘膜部位的 HPV DNA。由于口腔是 HPV 调节的一个未知部位，我们的研究是开发控制口腔 HPV 和预防 OPC 疗法的关键。