UNC CASCADE Network Research Base

摘要 世界卫生组织总干事呼吁消除浸润性宫颈癌（ICC） 到2030年感染艾滋病毒的妇女（WLWH）患ICC的风险高出约10倍。迫切需要高 直接适用于面临不同风险的WLWH的ICC预防最佳策略的质量证据 宫颈癌前病变和ICC的负担。 我们将在北卡罗来纳大学教堂山分校建立一个CASCADE网络UG 1研究基地（RB (UNC)以防止WLWH之间的ICC。本项目的总体目标是开发、测试和 实施有效的、可扩展的和具有成本效益的筛查和治疗策略，以减少 WLWH。我们将开发，实施和分析创新的混合动力的有效性，实施试验， CASCADE网络的重点领域是“改善筛查阳性的管理”和“优化癌前病变” 治疗”。该委员会将由临床医生、流行病学家、生物统计学家和培训专家组成 在LMIC和美国拥有数十年的ICC预防和HIV研究经验。我们的多学科 团队拥有实施科学、自动视觉评估（AVE）筛查、病理学 成本效益分析。 在目标1中，我们将开发CASCADE网络循证干预试验，以优化筛选 通过1）提供科学的，临床的和统计的 专业知识，开发创新的概念和协议，为新的，但务实的，混合的有效性- 实施试验，以及2）创建有组织的流程，以有效地开发概念和协议， 充分利用来自CNORB科学、统计、临床研究中心咨询、患者倡导的各种投入 咨询和科学咨询委员会。作为“改善”的潜在临床试验的说明性实例， 管理的屏幕阳性”，我们提出了协议1，一个阶梯楔形集群随机试验，以评估 在HPV阳性WLWH中，AVE分诊与HPV-和-治疗用于预防CIN 2+。对于“优化预癌 治疗”，我们提出了协议2，一个混合1型试验，以评估有效性的辅助，自我， 在原发性2/3治疗后给予阴道内局部治疗，以预防CIN 2+复发， WLWH。这两项试验的结果将包括癌前病变的临床有效性、实施结果和 成本效益分析。在目标2中，我们将确保成功实施和分析CASCADE 通过提供科学、临床和统计专业知识、运营支持和监管， 上级要员在目标3中，我们将为UG 1临床提供严格的基础临床和研究培训 研究中心和早期研究者设计和实施临床有效性研究。如果成功， CASCADE试验结果将推进LMIC和United地区WLWH的临床筛查和治疗指南 States.

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.