The overall goal of The CASCADE CLIMB (Cervical cancer prevention in women Living with HIV (WLWH) research Mobilization Base) is to generate critical evidence to inform optimization, implementation, and scale- up of effective cervical cancer prevention interventions for WLWH. Functioning as a scientific hub of the CASCADE Network, CLIMB will drive the network's scientific agenda through skilled and innovative scientific and statistical leadership, rigorous and robust operational oversight, and training and capacity-building opportunities to facilitate research, implementation, and scale-up of cervical cancer prevention interventions in intended-use settings. Our highly capable team of investigators has complimentary and integrated multidisciplinary research and clinical expertise in HPV/cervical cancer prevention and control, gynecologic oncology, women's health, and HIV/AIDS; methodological expertise in epidemiology, statistics, and implementation science; and a strong record of leading clinical trials and studies across the continuum of effectiveness to implementation research in both the US and in low- and middle-income countries (LMICs). The specific aims are to: 1) Develop and conduct rigorous pragmatic, multi-site clinical trials that address unmet needs in cervical cancer prevention for WLWH, and 2) Nurture emerging investigators in resource-limited settings by offering mentorship, capacity-building opportunities and training in the skills and disciplines needed to lead future research in cervical cancer prevention. We will develop trial concepts and protocols and lead implementation, operational oversight, statistical analysis, and manuscript preparation for three trials. We propose pragmatic trials to evaluate important clinical effectiveness and implementation outcomes in the US and in LMICs, with the following aims: 1) Compare strategies for offering HPV self-sampling vs. local standard of care screening approaches on rates of screening and precancer detection; 2) Compare molecular triage (e.g., p16/ki-67 dual stain, methylation) vs. immediate ablation after an HPV-positive result on follow-up rates of HPV/precancer detection; 3) Compare a task shifting strategy to nurses with electronic quality assurance for same day cervical cancer screening and treatment vs. usual care procedures that require referral for follow-up on rates of screening and treatment; and 4) Compare thermal ablation vs. LEEP for treating precancers in WLWH with type 2 transformation zones on rates of post-treatment HPV detection/precancer recurrence. We will leverage the University of Washington Department of Global Health's Treatment, Research, and Expert Education and E-Learning Programs to deliver training and capacity-building activities to CASCADE Clinical Sites, including synchronous online courses in research fundamentals, virtual and on-site trainings to build research capacity, and on-site clinical training in cervical cancer prevention. We will promote development of early-career investigators through a CASCADE Scholars program, including training in epidemiology and statistics and mentorship for manuscript preparation.

We anticipate that the successful completion of our aims will advance clinical practice guidelines for cervical cancer prevention for WLWH in diverse geographic settings, influence public health policy, and ultimately reduce healthcare disparities.