HPV, HIV and Oral Microbiota Interplay in Nigerian Youth (HOMINY)

尼日利亚青少年中的 HPV、HIV 和口腔微生物群相互作用 (HOMINY)

• 批准号: 10528927
• 负责人: MODUPE COKER
• 金额: $ 74.38万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10528927
• 关键词: Adolescence; Adolescent; Adult; Affect; Africa South of the Sahara; Age; Anus; Bacteria; CD4 Positive T Lymphocytes; Cancer Patient; Cell Count; Cervical; Child; Childhood; Clinical; Data; Detection; Development; Disease; Eligibility Determination; Epidemiology; Exhibits; Exposure to; Foundations; Frequencies; Funding; Future; HIV; HIV Infections; HIV Seronegativity; HPV oropharyngeal cancer; Hemophilus; Human Papilloma Virus Vaccination; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Immune response; Immune system; Immunologic Markers; Immunologics; Impairment; Incidence; Individual; Infection; Inflammatory; Interleukin-10; Interleukin-6; Intervention; Investigation; Knowledge; Lactobacillus; Leptotrichia; Low Prevalence; Malignant Neoplasms; Measures; Mediating; Microbe; Molecular; Mothers; Mouth Diseases; National Institute of Dental and Craniofacial Research; Natural History; Neisseria; Network-based; Nigeria; Nigerian; Observational Study; Oral; Oral cavity; Oral health; Oral mucous membrane structure; Pathology; Pathway interactions; Patients; Pattern; Perinatal Exposure; Persons; Population; Predisposition; Prevention; Prevention strategy; Prevotella; Prospective Studies; Reaction; Regimen; Reporting; Risk; Risk Factors; Role; Salivary; Sampling; Shotguns; Taxonomy; Technology; Testing; Therapeutic Intervention; Time; Training; Translating; United States National Institutes of Health; Vaccination; Vaccines; Viral Load result; Whole-Genome Shotgun Sequencing; Woman; Youth; advanced analytics; aged; antiretroviral therapy; bacterial community; bacteriome; base; cancer epidemiology; cancer prevention; clinical practice; cohort; cytokine; deep learning algorithm; deep learning model; follow-up; high risk; inflammatory marker; innovation; intervention program; malignant mouth neoplasm; malignant oropharynx neoplasm; metagenomic sequencing; microbial; microbial community; microbiome; microbiota; neural network; oral HPV; oral HPV infection; oral lesion; oral microbial community; oral microbiome; perinatal HIV; predictive modeling; prevent; preventive intervention; prospective; recruit; saliva sample; sex; sexually active; treatment strategy; tumor

PROJECT SUMMARY Despite antiretroviral therapy, people living with HIV (PLWH) have an increased risk of acquiring oral HPV and ultimately developing HPV-associated oral and oropharyngeal cancers compared to uninfected groups. While efforts are being made to understand the epidemiology of HPV-at-risk adult populations, the natural history of oral HPV in children and adolescents is largely uninvestigated. Determining the natural history of oral HPV infection in childhood and adolescence is critical in mitigating long-term risk and targeting vaccine intervention programs. Furthermore, the mechanisms underlying the persistence of oral HPV infection in PLWH are unclear, yet crucial to preventing HPV-associated cancers and diseases. Recent studies of the impact of HIV infection on the oral microbiome have shown differences in abundance of certain bacteria as compared HIV+ and HIV- children. Yet, there is limited understanding regarding the key microbial functional pathways that could facilitate oral HPV infection. The overall objectives of this project are to investigate the natural history of oral HPV infection and determine the taxonomic and functional roles of the oral microbiome in HPV persistence in the context of perinatal HIV exposure, infection, and treatment. To accomplish this, we will take advantage of a unique and large cohort of children/adolescents born to HIV-infected mothers vs. those born to HIV uninfected mothers. The proposed prospective observational study will recruit three groups of children and their respective mothers in Nigeria. Namely: 1) HIV-infected (HI), 2) HIV exposed-and-uninfected (HEU) and 3) HIV-unexposed-and- uninfected (HUU) children. The central hypothesis is that HI and HEU children, compared to HUU children, will have higher rates of oral HPV type-specific persistence, which is associated with a distinct microbial community and functional pathways. We will test this hypothesis via three specific aims: 1) Characterize and compare the natural history of oral HPV infection among youth born to HIV-infected women and uninfected women; 2) Identify inflammatory-mediated functional pathways associated with oral HPV persistence in children infected with HIV; and 3) Develop and test a deep learning algorithm based on clinical and oral taxonomic/functional microbiome profiles to predict oral HPV persistence. For the first aim, oral rinse samples from child-mother pairs will be used to characterize the dynamics of oral HPV subtype distribution over 2 years of follow-up. The second aim involves functional characterization of the oral microbiome using whole genome (shotgun sequencing) to investigate its relationship with HPV-type-specific persistence. For the third aim, we will train neural networks based on longitudinal microbiome features, cytokine levels, and other risk factors to determine which features strongly predict oral HPV. This project will lead to a more complete understanding of how impaired immunological states increase susceptibility to oral HPV infection and persistence. Knowledge gained regarding the contribution of oral microbiota, will lay a foundation for future prevention and therapeutic interventions.

项目摘要 尽管抗逆转录病毒疗法，但艾滋病毒（PLWH）的患者仍有增加口服HPV和的风险 与未感染的组相比，最终发展了与HPV相关的口服和口咽癌。尽管 正在努力了解HPV-AT风险成人人群的流行病学，这是自然历史 儿童和青少年的口服HPV在很大程度上没有评估。确定口腔HPV的自然历史 儿童和青春期感染对于缓解长期风险和靶向疫苗干预至关重要 程序。此外，PLWH中口服HPV感染持续性的基础机制尚不清楚， 但对于防止与HPV相关的癌症和疾病至关重要。最近关于HIV感染对 口服微生物组显示出某些细菌的丰度差异，因为HIV+和HIV- 孩子们。但是，人们对可能有助于促进的关键微生物功能途径的理解有限 口服HPV感染。该项目的总体目标是调查口服HPV感染的自然史 并确定口腔微生物组在HPV持久性中的分类学和功能作用 围产期HIV暴露，感染和治疗。为此，我们将利用独特的和 艾滋病毒感染的母亲与艾滋病毒未感染的母亲所生的大量儿童/青少年相比。这 拟议的前瞻性观察研究将招募三组儿童及其各自的母亲 尼日利亚。即：1）感染了HIV的（HI），2）暴露于HIV（HEU）和3）艾滋病毒无暴露和 - 未感染的（胡）儿童。中心假设是，与Huu儿童相比，HI和HEU儿童将 口服HPV类型特异性持久性的率较高，这与独特的微生物群落有关 和功能途径。我们将通过三个特定目的检验该假设：1）表征和比较 感染了艾滋病毒的妇女和未感染的妇女的青年口腔HPV感染的自然历史； 2）识别 感染HIV的儿童口服HPV持久性相关的炎症介导的功能途径； 3）基于临床和口服分类/功能性微生物组开发和测试深度学习算法 概况以预测口服HPV持久性。为了第一个目标，将使用子女对的口头冲洗样品 为了表征在2年的随访中口服HPV亚型分布的动力学。第二个目标涉及 使用整个基因组（shot弹枪测序）对口服微生物组的功能表征来研究其 与HPV型特异性持久性的关系。对于第三个目标，我们将根据 纵向微生物组特征，细胞因子水平和其他风险因素，以确定哪些特征强烈 预测口服HPV。该项目将使对免疫状态受损的方式有更全面的了解 增加对口服HPV感染和持久性的敏感性。关于贡献的知识 口服微生物群将为将来的预防和治疗干预奠定基础。