As millions of Africans living with HIV (LWH) live longer due to effective antiretroviral therapy (ART), their incidence of diseases of aging, including cancer, is increasing. Human papillomavirus (HPV) is the causal agent for almost all cervical and anal cancers, and ~50% of head and neck cancers. Cervical cancer, an AlDS- defining malignancy, is a leading cause of cancer deaths in women worldwide. The transforming capability of HPV is enhanced in women LWH (WLWH), whose HPV-related cervical lesions are more prevalent, more likely to progress, and more likely to become cancer. HPV also causes transformation of the anal mucosa. Men who have sex with men (MSM) constitute a substantial proportion of persons living with HIV (PLWH) around the world, and the incidence of HPV-related anal cancer is growing among MSM living with HIV. The incidence of cervical and anal cancers has not declined with the introduction of ART and remains elevated several fold in women and men LWH. We propose to establish an HIV-Associated HPV-related Malignancies Research Center (HAMRC) in Rwanda and the Democratic Republic of Congo (DRC), a partnership of four institutions: Albert Einstein College of Medicine, the University of Rwanda (UR), Rwanda Military Hospital (major teaching hospital for UR), and Université Protestante au Congo (UPC), to investigate HIV/HPV related cancers in Africa. This is an extension of our current U54-funded Rwanda/Einstein Research Consortium for HIV/HPV Malignancies, which has been highly successful in performing high-value rigorous research and developing laboratory and investigator research capacity. We will build upon and strengthen our existing partnerships to create a dynamic, integrated and flexible platform with academic, clinical and administrative expertise to support and foster the growth of scientific knowledge in HPV-related cancers in PLWH. We propose two research projects to be conducted over five years that can quickly impact the prevention of HIV/HPV cancers by supporting evidence-based decision-making to improve health outcomes: 1.) population based effectiveness of HPV vaccination in Rwandan women; and 2.) HPV prevalence and disease burden in men who have sex with men (MSM) in DRC and Rwanda. Embedded in both of these projects will be studies of the interaction of the local microbial flora with cervicovaginal, anal, and penile HPV infection. We propose to support both projects by developing laboratory capacity in molecular diagnostics in DRC, and in next generation sequencing (NGS) in Rwanda. Leadership will be provided by a team of four multiple principal investigators (MPIs): Kathryn Anastos MD, Leon Mutesa MD PhD, Marcel Yotebieng MD PhD, and Philip Castle PhD MPH, bringing strong experience in each or our three countries, Rwanda, DRC and the United States. Our Center, a collaboration of US, Rwandan and DRC institutions will serve as a national and regional resource hub in research, training, and career development for Af...