Cooperative Agreement U24CA275417

CASCADE COORDINATING CENTER - PROJECT SUMMARY/ABSTRACT WOMEN LIVING WITH HIV (WLWH) HAVE A HIGHER RISK FOR ACQUISITION, PERSISTENCE, AND PROGRESSION OF CERVICAL HUMAN PAPILLOMAVIRUS (HPV) TO PRECANCEROUS LESIONS, WHICH, IN THE ABSENCE OF EFFECTIVE SCREENING AND TREATMENT SERVICES, CAN PROGRESS TO INVASIVE CANCER AT FIVE-TO-SIX TIMES HIGHER RATES THAN IN WOMEN WITHOUT HIV. THE MASSIVE GLOBAL MOBILIZATION OF HUMANITARIAN RESOURCES SPANNING OVER THE PAST COUPLE OF DECADES, THROUGH INITIATIVES SUCH AS THE US PRESIDENT'S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR), HAS RESULTED IN MILLIONS OF WLWH IN LOW- AND MIDDLE-INCOME COUNTRIES (LMICS) NOW ACCESSING AFFORDABLE ANTIRETROVIRAL THERAPY AND CONSEQUENTLY LIVING LONGER LIVES. YET, THEIR RISK FOR CERVICAL CANCER CONTINUES UNABATED SINCE EFFECTIVE SCREENING AND PRE-CANCER TREATMENT SERVICES REMAIN UNAVAILABLE IN MOST LMICS. THE HIV/CERVICAL CANCER PREVENTION "CASCADE" CLINICAL TRIALS NETWORK PLANS TO CONDUCT PRAGMATIC CLINICAL TRIALS EVALUATING THE EFFECTIVENESS OF CLINICALLY PROVEN INTERVENTIONS TO OPTIMIZE THE CERVICAL CANCER SCREENING, MANAGEMENT, AND PRE-CANCER TREATMENT CASCADE FOR WLWH. THESE CLINICAL TRIALS WILL BE CONDUCTED IN INTENDED- USE ENVIRONMENTS IN RESOURCE-CONSTRAINED SETTINGS IN LMICS AND IN REGIONS WITH HEALTH DISPARITIES IN THE UNITED STATES. THE CASCADE NETWORK WILL HAVE FOUR MAJOR SCIENTIFIC FOCUS AREAS: INCREASING SCREENING UPTAKE, IMPROVING MANAGEMENT OF SCREEN POSITIVES, FACILITATING PRE-CANCER TREATMENT ACCESS, AND OPTIMIZING PRE-CANCER TREATMENT FOR CERVICAL CANCER PREVENTION IN WLWH. THE CASCADE NETWORK CLINICAL TRIALS WILL FOCUS ON THE MEASUREMENT OF THE CLINICAL EFFECTIVENESS OF INTERVENTIONS IN INTENDED USE SETTINGS WHILE GATHERING CRUCIAL INFORMATION INFORMING THE IMPLEMENTATION AND SCALE-UP OF SUCH INTERVENTIONS ACROSS THE CASCADE OF SCREENING AND PRE-CANCER TREATMENT FOR WLWH. SUCH HYBRID EFFECTIVENESS-IMPLEMENTATION DESIGNS WILL PRIMARILY FOCUS ON CLINICAL EFFECTIVENESS ENDPOINTS SUCH AS HPV POSITIVITY RATES AND/OR PRE-CANCER DETECTION/INCIDENCE/RECURRENCE RATES AND WILL SECONDARILY GATHER DATA ON IMPLEMENTATION-INFORMING ASPECTS SUCH AS COSTS, ACCEPTABILITY, AND INTERVENTION FIDELITY WHILE STUDYING IMPLEMENTATION STRATEGY. TO SUPPORT THE CASCADE CLINICAL TRIALS NETWORK IN PARTNERSHIP WITH THE NCI'S DIVISION OF CANCER PREVENTION, CASCADE RESEARCH BASES AND CASCADE CLINICAL SITES, THE CASCADE NETWORK COORDINATING CENTER WILL (I) PROVIDE OVERALL NETWORK COORDINATION AND FACILITATE SCIENTIFIC REVIEW OF NETWORK CLINICAL TRIAL CONCEPTS AND PROTOCOLS, (II) PROVIDE CENTRALIZED SUPPORT FOR DATA MANAGEMENT FOR NETWORK CLINICAL TRIALS, AND (III) CONDUCT INDEPENDENT RISK-APPROPRIATE AUDITING OF NETWORK CLINICAL TRIALS. THE CASCADE NETWORK COORDINATING CENTER WILL SERVE AS THE ORGANIZATIONAL AND COORDINATION HUB FOR THE CASCADE NETWORK AND PROVIDE MULTI-DISCIPLINARY EXPERTISE IN PROGRAM AND OPERATIONS MANAGEMENT, CLINICAL RESEARCH INFORMATICS/INFORMATION TECHNOLOGY, AND CLINICAL TRIALS AUDITING.