Partnership to Assess Viral and Immune Landscape Intersections with ONcology for People Living with HIV (PAVILION)

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PROJECT SUMMARY – OVERALL The partnership center, entitled Partnership to Assess Viral and Immune Landscape Intersections with Oncology (PAVILION) for People Living with HIV Program will bring together experienced research sites and world- renowned HIV, human papillomavirus (HPV), Epstein Barr Virus (EBV), and cancer researchers to offer a novel contribution to the HIV-Associated Malignancies Research Center network. The PAVILION theme is research of understudied, virus-associated tumors that disproportionately impact men and women living with HIV in sub-Saharan Africa (SSA). SSA remains home to two thirds of people living with HIV (PLWH). HIV-related immunosuppression results in an inability to control viruses and therefore a higher risk of virus-associated cancer, even among PLWH on effective antiretroviral therapy. The increasing life-expectancy of PLWH compounds this cancer risk as cancer is now a leading cause of mortality among PLWH in both high and low resource countries. Furthermore, PLWH experience poorer cancer treatment outcomes. Despite this, few studies of cancer etiology and cancer outcomes among PLWH in LMICs have been conducted, with little focus on HPV cancers at extra-cervical anatomic sites and very few studies of a suspected viral etiology for conjunctival tumors. PAVILION will therefore focus on the full range of cancers caused by HPV (anal, cervical, oropharyngeal, penile, and vulvar cancers) and the potential role of EBV in conjunctival squamous cell carcinoma - cancers that are disproportionality higher among PLWH, and which result in substantial morbidity and mortality. The overall goal of PAVILION is to provide the data necessary to inform prevention and therapeutic strategies to reduce the burden of cancers among PLWH in SSA. PAVILION includes partners in South Africa and Zimbabwe, multiple institutions in the US, and the DKFZ in Germany. Notably, Zimbabwe and South Africa have among the highest prevalence of HIV in Africa and have a rapidly increasing cancer burden that is largely comprised of infection-associated cancers. As a partnership, we have long standing collaborations, outstanding research leadership, mutual prioritization of the cancers to study, and institutional and consortium experience that will facilitate translation of scientific findings to achieve our goal. Specific Aims supporting this goal are: Aim 1: Establish a multi-national partnership with research infrastructure (Administrative & Coordinating, Central Laboratory, and Data Management & Statistics Cores) to conduct collaborative, innovative, and impactful research that advances prevention and treatment of infection-related cancers among PLWH in SSA Aim 2: Understand the fraction of tumors attributable to specific oncogenic viruses (i.e., HPV, EBV), the characterization of the immune microenvironment of tumors unique to the setting of HIV, and a more complete understanding of clinical outcomes for PLWH and cancer in SSA (Projects 1 and 2) Aim 3: Build capacity through active mentorship and training programs (Administrative & Coordinating and Developmental Cores) for early stage and junior faculty at partnership institutions