Multi-Omics Predictors of Oral HPV Outcomes among PLWH

PLWH 口腔 HPV 结果的多组学预测

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT Advances in antiretroviral therapy (ART) have not reduced the disproportional incidence and prevalence of oral human papilloma virus (HPV) and oropharyngeal cancers in people living with HIV (PLWH), suggesting ART alone may not fully restore mucosal immunity. This may be because HIV alters the oral microbiome, affecting mucosal immunity, and biological aging, such as changes in DNA methylation and immune senescence, can worsen HIV-associated immunosuppression. Reshaping the microbiome or reprogramming DNA methylation patterns may be a safe way to identify, prevent, or treat HPV persistence; however, understanding how these factors interact to promote cancer is a crucial gap in our existing knowledge. Our objective is to investigate these two biological processes (oral microbiome, biological aging), combined with socioeconomic and behavioral factors (sexual practices, lifestyle factors) to determine the impact of the natural history of HPV infection in PLWH, and to construct a machine learning classifier using these factors that can predict HPV infection and persistence. Our overarching hypothesis is that dysbiosis of the oral microbiome and older methylation aging are risk factors for HPV-related complications and can dampen the mucosal immune response in PLWH. Therefore, this proposed longitudinal study plans to collect saliva at two time points (baseline and after six months) from 150 virologically suppressed PLWH (men and women, ≥21 years old) from Puerto Rico CoNCRA, a community-based organization specialized in the prevention and treatment of HIV. PLWH who attend PR CoNCRA constitute a unique high-risk group where the prevalence of both HIV and oral HPV infection is higher, allowing our team of experts in HIV, HPV, epidemiology, cancer biology, oral health and bioinformatics to establish these relationships with high efficiency. The specific aims of this proposal are: (1) to determine how HPV incident infection and persistence affects the oral microbiome and oxidative stress in saliva in PLWH, (ii) to characterize the oral methylome of PLWH with and without HPV and assess the impact of methylation aging in the natural history of HPV infection, and (iii) to construct a diagnostic and prognostic classifier based on biological data (microbiome and methylation) and socio-behavioral characteristics capable of discriminating HPV infection and persistence among PLWH. We will characterize the oral microbiota by 16S rDNA sequencing, HPV genotypes by PCR, DNA methylation by Illumina Infinium Methylation BeadChip arrays and oxidative stress by immuno spectrophotometry assays. Additionally, remaining saliva and voluntary blood collection will be used to create a biorepository for future research. This study leverages resources from the UPRCCC and CePCHE including (i) the UPRCCC Biobank for the biospecimen storage, (ii) the Biostatistics and Bioinformatics Core for assistance in the analyses and storage of the data generated, and (iii) the Outreach Core to help with participant recruitment and promotion of his project. This study will also provide data needed for R01 submission, and graduation of Dr. Josué Pérez-Santiago as a project leader of CePCHE.
项目总结/摘要 抗逆转录病毒治疗(ART)的进展并没有减少口服抗逆转录病毒药物的不成比例的发病率和患病率。 人类乳头状瘤病毒(HPV)和口咽癌的艾滋病毒感染者(PLWH),建议ART 单独使用不能完全恢复粘膜免疫。这可能是因为HIV改变了口腔微生物组, 粘膜免疫和生物老化,如DNA甲基化和免疫衰老的变化,可以 加重艾滋病相关的免疫抑制。重塑微生物组或重新编程DNA甲基化 模式可能是识别,预防或治疗HPV持续性的安全方法;然而,了解这些模式是如何发生的, 因素相互作用,促进癌症是我们现有知识的一个关键空白。我们的目标是调查 这两个生物过程(口腔微生物组,生物老化),结合社会经济和行为 因素(性行为,生活方式因素),以确定HPV感染的自然史的影响, PLWH,并使用这些因素构建机器学习分类器,可以预测HPV感染和 坚持不懈我们的总体假设是,口腔微生物组的生态失调和老年甲基化老化 是HPV相关并发症的危险因素,并可抑制PLWH的粘膜免疫反应。 因此,这项纵向研究计划在两个时间点(基线和6个月后)收集唾液。 来自波多黎各CoNCRA的150例病毒学抑制的PLWH(男性和女性,≥21岁), 一个专门从事艾滋病毒预防和治疗的社区组织。参加公共关系的艾滋病毒携带者 CoNCRA构成了一个独特的高危人群,其中HIV和口腔HPV感染的患病率更高, 使我们的HIV、HPV、流行病学、癌症生物学、口腔健康和生物信息学专家团队能够 以高效率建立这些关系。本建议的具体目标是:(1)确定如何 HPV偶发感染和持续性影响PLWH中口腔微生物组和唾液中的氧化应激,(ii) 表征有和没有HPV的PLWH的口腔甲基化组,并评估甲基化老化对 HPV感染的自然史,以及(iii)构建基于生物学的诊断和预后分类器 能够区分HPV感染的数据(微生物组和甲基化)和社会行为特征 而在《易经》中,我们将通过16 S rDNA测序、HPV 基因型通过PCR、DNA甲基化通过Illumina Infinium甲基化BeadChip阵列和氧化应激通过 免疫分光光度测定。此外,剩余的唾液和自愿血液收集将用于 为未来的研究建立一个生物储存库。这项研究利用了UPRCCC和CePCHE的资源 包括(i)用于生物样本储存的UPRCCC生物库,(ii)用于生物样本储存的生物统计学和生物信息学核心, 协助分析和储存所产生的数据,以及(iii)外联核心,以帮助参与者 招聘和推广他的项目。本研究还将提供R 01提交所需的数据,以及 Josué Pérez-Santiago博士毕业,担任CePCHE项目负责人。

项目成果

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Josue Perez-Santiago其他文献

Josue Perez-Santiago的其他文献

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{{ truncateString('Josue Perez-Santiago', 18)}}的其他基金

Cross Sectional Association of the Oral Microbiota and the Inflammasome with Oral HPV among HIV+ Adults
HIV 成人口腔微生物群和炎症小体与口腔 HPV 的横断面关联
  • 批准号:
    10447167
  • 财政年份:
    2021
  • 资助金额:
    $ 27.4万
  • 项目类别:
Cross Sectional Association of the Oral Microbiota and the Inflammasome with Oral HPV among HIV+ Adults
HIV 成人口腔微生物群和炎性体与口腔 HPV 的横断面关联
  • 批准号:
    10669316
  • 财政年份:
    2021
  • 资助金额:
    $ 27.4万
  • 项目类别:
Cross Sectional Association of the Oral Microbiota and the Inflammasome with Oral HPV among HIV+ Adults
HIV 成人口腔微生物群和炎症小体与口腔 HPV 的横断面关联
  • 批准号:
    10305164
  • 财政年份:
    2021
  • 资助金额:
    $ 27.4万
  • 项目类别:
Short Chain Fatty Acids: Route for Facilitation of Oral HPV via Inflammasome Dysregulation in People Living with HIV
短链脂肪酸:通过 HIV 感染者炎症小体失调促进口腔 HPV 的途径
  • 批准号:
    10532974
  • 财政年份:
    2021
  • 资助金额:
    $ 27.4万
  • 项目类别:

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