UNC CASCADE Network Research Base

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ABSTRACT The Director-General of the World Health Organization has called for invasive cervical cancer (ICC) elimination by 2030. Women living with HIV (WLWH) have a ~10-fold higher risk of ICC. There is an urgent need for high quality evidence on optimal strategies for ICC prevention directly applicable to WLWH who face a disparate burden of cervical precancer and ICC. We will establish a CASCADE Network UG1 Research Base (RB) at the University of North Carolina-Chapel Hill (UNC) to prevent ICC among WLWH. The overarching goal of this UNC RB proposal is to develop, test, and implement effective, scalable, and cost-effective screening and treatment strategies to reduce ICC among WLWH. We will develop, implement, and analyze innovative hybrid effectiveness-implementation trials in the CASCADE Network focus areas of “Improving the Management of Screen Positives” and “Optimizing Precancer Treatment”. The UNC RB will be composed of clinicians, epidemiologists, biostatisticians, and training experts with decades of research experience on ICC prevention and HIV in both LMIC and the US. Our multi-disciplinary team has expertise in implementation science, screening with automated visual evaluation (AVE), pathology, and cost-effectiveness analyses. In Aim 1, we will Develop CASCADE Network trials of evidence-based interventions to optimize the screening for and management of cervical precancer among WLWH by 1) providing scientific, clinical and statistical expertise to develop innovative concepts and protocols for novel, yet pragmatic, hybrid effectiveness- implementation trials, and 2) creating organized processes to efficiently develop concepts and protocols by leveraging diverse input from the UNC RB Scientific, Statistical, Clinical Sites Advisory, Patient Advocacy Advisory, and Scientific Advisory Committees. As an illustrative example of a potential clinical trial for “Improving Management of Screen-Positives”, we propose Protocol 1, a stepped wedge cluster randomized trial to Evaluate AVE triage versus HPV-and-treat among HPV-positive WLWH for CIN2+ prevention. For “Optimizing Precancer Treatment”, we propose Protocol 2, a Hybrid Type 1 trial to evaluate the effectiveness of adjuvant, self- administered intravaginal topical therapy following primary 2/3 treatment to prevent CIN2+ recurrence among WLWH. Outcomes for both trials will include clinical effectiveness for precancer, implementation outcomes, and cost effectiveness analyses. In Aim 2, we will ensure successful Implementation and Analysis of CASCADE Network trials by providing scientific, clinical and statistical expertise, operational support, and regulatory oversight. In Aim 3, we will provide Rigorous Foundational Clinical and Research Training for UG1 Clinical Sites and Early-Stage Investigators to design and implement clinical effectiveness research. If successful, CASCADE Trial findings will advance clinical screening and treatment guidelines for WLWH in LMIC and United States.