This application is to establish the UNC-Malawi Cancer Consortium (UNC-MCC), to develop capacity and conduct high-impact research focused on HIV-associated cancers. The consortium builds on longstanding collaborations between the University of North Carolina at Chapel Hill, Lighthouse Trust, Malawi Ministry of Health, and University of Malawi College of Medicine. These partnerships have resulted in internationally recognized contributions for HIV care and prevention in sub-Saharan Africa. Achievements have been made possible by leadership and participation in NIH networks conducting clinical trials and epidemiologic research in the region. This infrastructure can now be leveraged for HIV-associated malignancies, which are overwhelming contributors to cancer burden in Malawi even after antiretroviral therapy (ART) scale-up. UNCMCC is focused on the herpes virus-associated cancers, Kaposi sarcoma (KS), and lymphoma. Our consortium will be led by three principal investigators with highly complementary expertise (Satish Gopal MD, clinical research; Sam Phiri PhD, implementation science; Blossom Damania PhD, virology). It will include three support cores (Administrative/Coordinating, Mentoring/Career Development, Applied Analytics) and three research projects. The three research projects include: (1) a record linkage study between the Malawi National Cancer Registry and large HIV cohorts to clarify changing patterns of cancer risk in the ART era; (2) a cohort study to elucidate KS subsets to improve outcomes; and (3) a cohort study to develop risk-adapted, response-guided treatment of HIV-associated lymphoma. To support consortium objectives, a diverse team of investigators has been assembled spanning the clinical, population, and basic sciences, and includes Malawian and US scientific leaders, as well as other select international collaborators. The consortium will enhance existing administrative, operational, and research relationships between all partnering institutions and investigators. The External Advisory Board and Scientific Advisors will ensure that the consortium remains highly responsive to community needs in Malawi, while also addressing urgent research questions facing the international HIV-associated cancer community. A focus is to develop sufficient internal capacity such that Malawi can become a leading country for HIV-associated cancer research, as it has long been for HIV care and treatment. Building on prior successes and partnerships outlined in this application, UNC-MCC is extremely well-positioned to catalyze a broad, coordinated, cancer control effort in Malawi, and advance the overall NCI scientific agenda for sub-Saharan Africa.