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

项目简介:

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.