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: 10703511
• 负责人: Anna R. Giuliano
• 金额: $ 66.44万
• 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/10703511
• 关键词: Aberrant DNA Methylation; Acceleration; 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; Exclusion; Funding; Future; Goals; Grant; HIV; HIV therapy; 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; 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; biomarker identification; cancer risk; carcinogenesis; co-infection; disorder risk; efficacy evaluation; epigenetic marker; follow-up; high risk; human old age (65+); male; malignant mouth neoplasm; malignant oropharynx neoplasm; men; modifiable risk; multidisciplinary; novel; oral HPV; oral HPV infection; oral infection; premalignant; prevent; programs; progression risk; 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 类型引起， 对男性和艾滋病毒感染者 (PLWH) 的影响尤为严重。没有可靠的方法来检测OPC 癌前病变的二级预防。评估 9vHPV 疫苗预防 OPC 功效的试验 我们的团队正在进行以下项目：NCI 资助的 U54 资助、口腔癌和宫颈癌研究、HPV 和 HIV 的研究 美洲 [ROCCHHA] 针对 HIV 感染者的试验 201，以及针对未感染 HIV 的默克 v503-049 试验 男人。虽然 HPV 疫苗接种是 OPC 一级预防的一种很有前景的方法，但疫苗接种可能并不适用 为那些最需要帮助的人提供服务，因为大多数国家将男性排除在其国家计划之外，并且可能没有 艾滋病病毒感染者疫苗接种政策。预防 OPC 和识别感染风险最高的 PLWH 的其他方法 迫切需要进行监测，特别是考虑到 OPC 发病率在 美国和拉丁美洲。为预防策略提供信息，识别可改变的风险因素并轻松地 需要测量生物标志物来识别那些风险最高的人。 HPV 相关 OPC 的发展是多方面的 阶乘。导致口腔致癌 HPV 感染的性行为是一个必要的步骤。不管 根据感染的解剖部位，只有一部分感染持续存在并进展为癌症。多重互动 影响病毒持久性的因素。我们是少数进行大规模口服 HPV 自然检测的团体之一 历史研究对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、贫困 口腔健康、免疫失调（例如感染者中发生的情况）以及异常 DNA 甲基化会影响口腔 HPV 持续存在。雪上加霜的是，感染者寿命较长，导致终生免疫 功能障碍可能会加速生物衰老，增加获得或重新激活多种功能的风险 EBV 等感染，最终导致致癌病毒控制能力下降。社会因素加剧了这种情况 由于感染者对牙科护理和其他服务的利用率较低，导致口腔长期得不到治疗 感染、随后的慢性口腔炎症、牙周病和牙齿脱落，这些因素可能会导致 促进口腔 HPV 致癌，并与 HPV-OPC 风险独立相关。我们是 作为我们 ROCCHHA 拨款的一部分，在 PLWH 中开展两项大型研究，获取临床数据和口腔数据 在每两年一次的研究访视中收集漱口样本，我们将利用这些样本来研究口腔 HPV 自然史。目标是 该应用旨在定义 PLWH 中致癌性口腔 HPV 感染的自然史。中央 拉丁美洲艾滋病毒感染者口腔 HPV 研究 (ORAL H2) 研究的假设是： 在 PLWH 中，高生物年龄、牙齿健康和病毒因素与持续性口腔溃疡有关。 致癌性HPV。我们将估计口腔 HPV 16 和致癌性 HPV 感染，评估与病毒相关的因素 持久性，并确定预测口腔的生物标志物和行为因素的最佳组合 致癌性 HPV 持续存在。