Project Summary: For >18 years, Makerere and Johns Hopkins universities have partnered in Uganda to characterize the epidemiology of hepatitis B (HBV) and HIV co-infection, define the subsequent sequelae including hepatocellular carcinoma (HCC) and advance clinical management. Through an NCI-supported U54 program, we conducted one of the largest and well-characterized studies of HCC in Africa, recruiting from both central urban and northern rural regions of Uganda. Moreover, we have performed mixed-methods research to identify knowledge and clinical barriers to implementation of HBV screening and diagnosis within HIV care settings. Recently, our collaborative team successfully completed a demonstration project focused on integrating HBV diagnostic and treatment services into HIV care in the West Nile region and also launched an implementation assessment of antenatal care screening for and delivery of HepB birth dose vaccination at multiple sites across Uganda. Importantly, the burden and lethality of HCC can be successfully ameliorated with implementation of evidence- based and contextually appropriate prevention, screening, diagnostic and treatment interventions. However, these measures have not been comprehensively implemented into routine care settings in Uganda or other high HCC burden regions of sub-Saharan Africa. Leveraging this long-standing work in Uganda, our proposed bundle of interventions, the Liver Cancer Comprehensive Control (LC3) package, incorporates diagnostic testing and treatment of HBV, primary prevention through vaccination of susceptible adults, and referral for liver disease staging and active surveillance for early HCC detection among at-risk populations. We will integrate the LC3 package into existing HIV care delivery platforms among adults living with HIV in Uganda. Our overarching goal is to demonstrate the reach, effectiveness, and maintenance of delivering LC3 services within HIV care settings. Successful implementation of LC3 in Uganda will serve as a model for integrating complex cancer control intervention packages into existing HIV care delivery systems across similar countries in sub-Saharan Africa.