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

拉丁美洲艾滋病毒感染者的口腔 HPV 研究（ORAL - H² 研究）

• 批准号: 10528596
• 负责人: Anna R. Giuliano
• 金额: $ 71.84万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-12 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10528596
• 关键词: Aberrant DNA Methylation; Age; Aging; Alcohols; Americas; Anatomy; Area; Behavioral; Biological; Biological Aging; Biological Markers; CD4 Lymphocyte Count; Cancer Etiology; Chronic; Clinical; Clinical Data; Collaborations; Country; Data; Dental Care; Dental Hygiene; Development; Early Diagnosis; Funding; Future; Goals; Grant; HIV; HIV therapy; HIV-1; HPV oropharyngeal cancer; Human Herpesvirus 4; Human Papilloma Virus Vaccination; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune; Immune System Diseases; Incidence; Infection; Inflammation; Infrastructure; Integration Host Factors; Knowledge; Latin America; Latin American; Lead; Literature; Location; Malignant Neoplasms; Malignant neoplasm of anus; Malignant neoplasm of cervix uteri; Measures; Methods; Methylation; Natural History; Nested Case-Control Study; Oncogenic; Oral; Oral health; Patients; Periodontal Diseases; Persons; Policies; Population; Predictive Factor; Prevention; Prevention strategy; Primary Prevention; Prospective Studies; Recording of previous events; Reproducibility; Research; Risk; Risk Factors; Secondary Lesion; Secondary Prevention; Services; Sex Behavior; Specimen; Testing; Tobacco use; Tooth Loss; Tumor Suppressor Genes; Vaccination; Vaccines; Viral; Visit; Woman; cancer risk; cancer vaccination; carcinogenesis; co-infection; disorder risk; epigenetic marker; follow-up; high risk; male; malignant mouth neoplasm; malignant oropharynx neoplasm; men; modifiable risk; multidisciplinary; novel; oral HPV; oral HPV infection; oral infection; premalignant; prevent; programs; screening; social factors

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.

抽象的 口咽癌（OPC）主要由HPV 16和其他致癌HPV类型以及 不成比例地影响男性和艾滋病毒（PLWH）的人。没有可靠的方法来检测OPC 预防继发性病变。评估9VHPV疫苗功效以防止OPC的试验 我们的团队正在进行：NCI资助的U54赠款，口腔和宫颈癌的研究，HPV和HIV Americas [Rocchha]艾滋病毒男性中的2011年，艾滋病毒未感染的默克V503-049试验 男人。尽管HPV疫苗接种是主要预防OPC的有前途的方法，但疫苗可能不是 最需要的人可以使用，因为大多数国家都在其国家计划中排除了男性，并且可能没有 PLWH疫苗接种的政策。防止OPC并识别有最高风险的PLWH的其他方法 迫切需要监视，特别是考虑到OPC的发病率正在显着增加 我们和拉丁美洲。为了告知预防策略，识别可修改的风险因素和轻松 需要测量的生物标志物，以识别最高风险的生物标志物。与HPV相关的OPC的开发是多的 阶乘。导致口服致癌性HPV感染的性行为是必要的步骤。不管 解剖的感染部位，只有一定比例的感染持续并发展为癌症。多个相互作用 因素影响病毒持久性。我们是进行大型口服HPV自然的少数小组之一 历史研究为这一文献做出了贡献。我们和其他研究的结果表明，年龄较大，差 口腔健康，免疫失调，例如在PLWH中发生，异常DNA甲基化影响口服 HPV持久性。加剧这是一个事实，即PLWH生活到年长的年龄，从而导致终生免疫 可能加速生物衰老的功能障碍，增加获得或重新激活的风险 EBV等感染，最终导致致癌病毒控制降低。社会因素加剧了这个 PLWH的场景较低，对牙科护理和其他服务的利用率较低，导致未经治疗的口服延长 感染，随后的慢性口腔炎症，牙周疾病和牙齿脱落，可能是可能的因素 促进口服HPV癌变，并与HPV-OPC风险独立相关。我们是 在PLWH中进行了两项大型研究，作为我们的Rocchha赠款的一部分，这些研究获得了临床数据和口头 在两年一次的研究访问中gargle标本，我们将利用该研究来研究口腔HPV自然史。目标 该应用是为了定义PLWH中致癌口服HPV感染的自然史。中央 在艾滋病毒（口服H2）研究的拉丁美洲人中口头HPV研究的假设是 在PLWH高级生物年龄中，牙齿健康和病毒因素与持续的口服有关 致癌HPV。我们将估计口服HPV 16和致癌HPV感染，评估与病毒相关的因素 持久性，并确定预测口服的生物标志物和行为因素的最佳组合 致癌的HPV持久性。