Einstein/Rwanda/DRC Consortium for Research in HIV/HPV/ Malignancies

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PROJECT SUMMARY Sub-Saharan Africa carries a disproportionate burden of HIV, with 69% of infections globally, as well as a high burden of virally induced malignancies, even before the HIV epidemic. Currently a third of all cancers in Sub- Saharan Africa are virally induced. While data from Africa are scant, evidence from other parts of the world indicates that with increasing rates of treatment with combination antiretroviral therapy for persons living with HIV (PLWH), the incidence of HIV-associated malignancies (i.e., Kaposi’s Sarcoma, non-Hodgkin’s Lymphoma) has declined dramatically. However, cancers caused by human papillomavirus (HPV), specifically invasive cervical cancer and anal cancer, have not declined and may have increased. Investigations of HPV-related malignancies are heavily dependent on laboratory testing and histopathology, which can be implemented in resource limited settings. The Rwanda/DRC/Einstein HIV-Associated HPV- Malignancies Research Center (HAMRC) proposed in this application will extend both the geographic and the scientific scope of our research and capacity-building activities. We will leverage our existing HIV research partnerships in the Democratic Republic of Congo (DRC) to include much desired research capacity to assess HPV-related cancers in PLWH. The Center proposes major studies of HPV-related malignancies through two projects: 1) evaluating the impact of HPV prophylactic vaccination in young women living with HIV; and 2) assessing HPV infection and disease in Congolese (DRC) and Rwandan men who have sex with men with and without HIV infection. In both studies we will investigate the interactions of HPV infection and disease with the local microbial flora. The Shared Resources Core addresses the goal of the HAMRC by fostering sustainable research capacity in Rwanda and the DRC to support investigation of viral-associated cancers. Thus, the specific aims of the Shared Resources Core are to provide rigorous molecular diagnostic analyses to support studies of the impact of both HAMRC projects, and to increase capacity to conduct research in HPV-related malignancies in PLWH in Rwanda and the DRC, and will specifically: 1. Replicate in the Pathology Laboratory at Université Protestante au Congo, the real-time PCR platform for hrHPV typing previously established at Rwanda Military Hospital (RMH), in the Einstein/RMH Research Laboratory. 2. Develop at the Rwanda Military Hospital (RMH), in the Einstein/RMH Research Laboratory, and in collaboration with the University of Rwanda, next generation sequencing. 3. Support further development of ELISA testing in Rwanda, at the Einstein/RMH Research Laboratory, using an assay to measure anti-HPV16 and HPV18 IgG antibody titers implementing a protocol established by the Frederick National Laboratory of Cancer Research HPV Serology Laboratory. The proposed capacity building will include personnel development of both research staff and investigators and will efficiently leverage existing research infrastructure previously developed in large part by the efforts of the proposed HARMC leadership.