UNC CASCADE Network Research Base

摘要 世界卫生组织总干事呼吁根除浸润性宫颈癌 到2030年。艾滋病毒携带者(WLWH)患ICC的风险是女性的10倍。迫切需要高利率 直接适用于面临不同疾病的WLWH的ICC预防最佳策略的优质证据 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级联网络UG1研究基地(RB) (UNC)以防止WLWH中的ICC。该UNC RB提案的总体目标是开发、测试和 实施有效、可扩展且经济高效的筛查和治疗策略，以减少ICC 怎么了。我们将开发、实施和分析创新的混合有效性-实施试验 CASCADE网络重点加强阳性筛查管理和优化癌前病变 治疗“。UNC RB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和美国都有数十年的ICC预防和HIV研究经验。我们的多学科 团队在实施科学、自动视觉评估(AVE)筛查、病理学、 和成本效益分析。 在目标1中，我们将开发循证干预的级联网络试验，以优化筛查 WLWH中宫颈癌前病变的治疗和管理：1)提供科学、临床和统计 开发创新概念和协议的专业知识，以实现新颖而实用的混合效率- 实施试验，以及2)创建有组织的流程，以便通过以下方式有效地开发概念和协议 利用来自UNC RB科学、统计、临床站点咨询、患者倡导的不同意见 咨询委员会和科学咨询委员会。作为一个潜在的临床试验的说明性例子 对于筛查阳性的管理，我们提出了协议1，一种阶梯式楔形群随机试验来评估 在HPV阳性的WLWH中用于预防CIN2+的平均分流与HPV加治疗的比较。为“优化癌前状态” ，我们提出了方案2，一种混合的1型试验，以评估佐剂，自身- 首次2/3治疗后经阴道局部治疗预防CIN2+复发 怎么了。这两项试验的结果将包括癌症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，我们将确保级联的成功实施和分析 通过提供科学、临床和统计专业知识、运营支持和监管，实现网络试验 疏忽。在目标3中，我们将为UG1临床提供严格的基础临床和研究培训 网站和早期研究人员来设计和实施临床有效性研究。如果成功， 级联试验结果将推进LMIC和United的WLWH临床筛查和治疗指南 各州。

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.