Oral Papilloma Virus, Microbiota and Cancer in People Living with HIV (OHPVMC)

项目摘要： 来自低收入和中等收入人群的HIV感染者的口腔人乳头瘤病毒（OHPV）感染 艾滋病毒负担最重的国家（中低收入国家）由于与艾滋病毒/艾滋病有关， 癌症的发展。人类口腔中有500至700个物种的大群落（口腔 微生物群）已知：共生共存，从父母传给孩子，有种族差异 因此，本发明的组合物在预防疾病或引发/传播疾病方面具有重要作用。在这 我们的项目是为了前瞻性地了解口腔乳头状瘤病毒感染、口腔 微生物组和口腔病变，包括艾滋病毒感染者（PLWHIV）的癌症。多学科 来自乌干达坎帕拉马凯雷雷大学的一个项目小组将共同努力， Makerere附属的各诊所为大约20 000名艾滋病毒感染者提供服务， 大学通过其Makerere联合艾滋病计划（MJAP），以解决以下研究目标： 我们将描述和了解不同的PLWHIV中的致癌口腔人乳头瘤病毒感染。 我们将采用前瞻性队列设计来描述和了解OHPV的自然进展 艾滋病毒感染者。在目标2中，我们将确定PLWHIV与或 没有OPV。我们将前瞻性地比较口腔微生物组的变化，重点关注细菌 与牙周炎的PLWHIV，之前，期间和之后与OHPV感染。为了实现目标3， 确定OHPV，PLWHIV中口腔病变和癌症之间的关系。我们将使用一个前瞻性的 队列设计，比较PLWHIV感染前口腔乳头状瘤病毒感染的频率和严重程度， 在出现口腔病变期间和之后。每个子研究都建立在过去的研究基础上 在项目总监的领导下，团队的经验。项目 是创新的，由于计划使用高度敏感的现代分子技术，如下一步 世代排序，以前瞻性地观察，然后了解每一个下的相互作用 提出的目标。了解这些相互作用将构成实施有效的 预防或治疗策略/方法，如当地试验使用益生菌作为一种形式， 在该人群中进行替代治疗，以确定目前可用的人类替代疗法的新靶点。 乳头瘤病毒疫苗。总的来说，拟议的项目对公众健康具有重大意义。它 将提供解决口腔健康问题所需的先决条件结果数据、培训和基础设施， 乌干达和其他地球仪资源匮乏地区的艾滋病毒和艾滋病负担。

Project Abstract: Oral human papilloma virus (OHPV) infections in individuals with HIV from Low- and Middle-Income Countries (LMICs) that have the highest burden of HIV are a cause for concern due to their association with the development of cancers. The human oral cavity hosts a large community of 500 to 700 species (oral microbiota) known to: co-exist symbiotically, are transmitted from parents to children, have racially distinct composition and play an important role in the protection against or initiation/propagation of disease. In this project we set out to prospectively understand the interactions between oral papilloma virus infections, oral microbiome and oral lesions that include cancers in People living with HIV (PLWHIV). The multidisciplinary project team from Makerere University in Kampala Uganda, will work together to exploit the existing large low-resource setting of approximately 20,000 PLWHIV served by various clinics affiliated to Makerere University through its Makerere Joint Aids Program (MJAP) to address the following study aims: For aim 1 we will characterize and understand oncogenic oral human papilloma virus infections in different PLWHIV. We will use a prospective cohort design to characterize and understand the natural progression of OHPV infections in PLWHIV. In aim 2 we will determine the differences in the oral microbiome of PLWHIV with or without OHPV. We will prospectively compare the changes in oral microbiome with a focus on the bacteria associated with periodontitis in PLWHIV, before, during and after infections with OHPV. For aim 3 we will determine the associations between OHPV, Oral lesions and cancer in PLWHIV. We will use a prospective cohort design to compare the frequency and severity of oral papilloma virus infections in PLWHIV before during and after presentation with oral lesions. Each of the sub studies builds on the past research experiences of the team that has been put together under the leadership of the Project director. The project is innovative due to the planned use of the highly sensitive modern molecular techniques like next generation sequencing to prospectively observe then understand the interactions under each of the proposed aims. Understanding these interactions will form the basis for the implementation of effective preventive or treatment strategies/approaches like local trials on the use of probiotics as a form of replacement therapy in this population to identification of new targets for the currently available Human Papilloma virus vaccine. Taken together, the proposed project has substantial public health importance. It will provide the prerequisite outcomes data, training, and infrastructure needed to address the oral health and HIV burden in Uganda and other low resource settings across the globe.