Project Summary / Abstract Successful HIV treatment programs in Botswana and elsewhere in southern Africa have led to dramatic reductions in mortality from tuberculosis, cryptococcosis, and other non-cancer AIDS deaths. However, cancer deaths have not decreased, and cervical cancer now is the leading cause of death for women living with HIV in the region. Cervical cancer is preventable with early detection and treatment of precancerous lesions but challenges of limited access to initial screening, poor performance of initial screening technologies, high prevalence of cervical precancers, and persistent or relapsed dysplasia following therapy impair the impact of programs for women living with HIV. Working to develop strategies to these challenges, we will establish the Botswana CASCADE Clinical Trials Site at BHP that will participate in and contribute to the following high- impact areas of research: 1) Enhancing cervical precancer screening uptake through patient and context relevant approaches, including HPV self-sampling, non-clinical screening venues, and screening during antenatal care; 2) Strategies and novel technologies to improve management of positive HPV initial screening maximize prevention of invasive cancer while minimizing patient risk and consumption of health system resources; 3) Improving precancer treatment access, treatment completion, and outcomes; and 4) Optimizing treatment approaches to cervical precancers including comparative trials of ablation techniques, intervals of repeat evaluation, and vaccines or other immunologic therapies. The Botswana CASCADE Clinical Trials Site will contribute to conducting high-quality clinical research studies, provide context-relevant input on developing trial concepts, understand disparity in access by geography, economic factors, and language/ethnicity, and continue to develop local research capacity through mentoring and training.

Project Narrative The Botswana CASCADE Clinical Trials Site will study strategies for preventing cervical cancer in women living with HIV. Cervical cancer is the leading cause of death for women on HIV treatment in Botswana and current approaches have not succeeded in reaching population with effective preventative services. Studies to be conducted will focus on strategies to improve access to screening, effectiveness of cervical screening, and access and treatment effectiveness of identified precancers.