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

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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.