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)

基本信息

批准号：
10673097
负责人：
MODUPE COKER
金额：
$ 92.9万
依托单位：
RUTGERS BIOMEDICAL AND HEALTH SCIENCES
依托单位国家：
美国
项目类别：
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/10673097
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 Nigeria Nigerian Observational Study Oral Oral Characters 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 Shotgun Sequencing Shotguns Taxonomy Technology Testing Therapeutic Intervention Time Training Translating Tumor Promotion United States National Institutes of Health Vaccination Vaccines Viral Load result Woman Youth advanced analytics aged antiretroviral therapy bacterial community bacteriome 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 risk mitigation saliva sample sex sexually active treatment strategy whole genome

项目摘要

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.

项目概要尽管进行了抗逆转录病毒治疗，艾滋病毒感染者 (PLWH) 感染口腔 HPV 和与未感染人群相比，最终会患上 HPV 相关的口腔癌和口咽癌。尽管正在努力了解 HPV 高危成人人群的流行病学、HPV 感染的自然史儿童和青少年的口腔 HPV 基本上未经调查。确定口腔 HPV 的自然史儿童和青少年时期的感染对于减轻长期风险和有针对性的疫苗干预至关重要程序。此外，PLWH 口腔 HPV 感染持续存在的机制尚不清楚，但对于预防 HPV 相关癌症和疾病至关重要。 HIV感染对人的影响的最新研究与 HIV+ 和 HIV- 相比，口腔微生物组显示某些细菌的丰度存在差异孩子们。然而，对于可以促进的关键微生物功能途径的了解有限。口腔 HPV 感染。该项目的总体目标是调查口腔 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艾滋病毒暴露、感染和治疗。为了实现这一目标，我们将利用独特的优势感染艾滋病毒的母亲所生的大量儿童/青少年与未感染艾滋病毒的母亲所生的儿童/青少年。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) HIV 感染者 (HI)、2) HIV 暴露但未感染 (HEU) 以及 3) HIV 暴露和未感染者未感染（HUU）的儿童。核心假设是，与 HUU 儿童相比，HI 和 HEU 儿童将口腔 HPV 类型特异性持续率较高，这与独特的微生物群落有关和功能途径。我们将通过三个具体目标来检验这一假设：1）描述并比较感染艾滋病毒的妇女和未感染艾滋病毒的妇女所生的青少年口腔 HPV 感染的自然史； 2）识别与感染 HIV 的儿童口腔 HPV 持续存在相关的炎症介导的功能途径； 3) 开发和测试基于临床和口腔分类/功能微生物组的深度学习算法来预测口腔 HPV 持续性。对于第一个目标，将使用来自母婴的口腔冲洗液样本描述 2 年随访期间口腔 HPV 亚型分布的动态特征。第二个目标涉及使用全基因组（鸟枪测序）对口腔微生物组进行功能表征，以研究其与 HPV 类型特异性持久性的关系。对于第三个目标，我们将训练基于纵向微生物组特征、细胞因子水平和其他危险因素，以确定哪些特征强烈预测口腔 HPV。该项目将导致人们更全面地了解免疫状态受损的情况增加口腔 HPV 感染的易感性和持久性。获得的有关贡献的知识口腔微生物群，将为未来的预防和治疗干预奠定基础。