A Randomized Clinical Trial to Assess the Effectiveness of Ablative Treatments for Cervical Cancer Risk Reduction in HIV+ Women living in Mozambique

一项随机临床试验，旨在评估消融治疗对莫桑比克艾滋病毒妇女降低宫颈癌风险的有效性

• 批准号: 10430798
• 负责人: Kathleen Schmeler
• 金额: $ 69.53万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-12 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10430798
• 关键词: Randomized; Clinical; Trial; Assess; Effectiveness

Invasive cervical cancer is the 4th most common cancer and cause of cancer-related mortality in women worldwide. Low- and middle-income countries (LMICs) experience almost 90% of the global cervical-cancer burden, with sub-Saharan Africa (SSA) experiencing the highest rates of cervical cancer. Human immunodeficiency virus (HIV) infection, which also disproportionately affects SSA, greatly increases the risk of cervical cancer. The World Health Organization now has a call-to-action for the elimination of cervical cancer, which includes vaccination young adolescents against human papillomavirus (HPV), the obligate viral cause of cervical cancer, and screening mid-adult women for the early detection and treatment of cervical abnormalities before becoming cancerous. However, both the best strategy for treating cervical abnormalities in women living with HIV (WLWH) from SSA and how to mitigate treatment failures are unknown. To address this gap in knowledge, we propose a randomized clinical trial to assess the treatment effectiveness of two ablative methods of treatment, gas-based cryotherapy and thermocoagulation, for treatment of CIN2/3 and high-risk HPV in WLWH women. Eligible, confirmed WLWH women (n=5,014), ages 25-49 years, and living in Maputo, Mozambique, in conjunction with the local PEPFAR (President's Emergency Plan For AIDS Relief) program, will be recruited to participate in this trial when attending their routine HIV-care visit. Consenting WLWH will be screened by rapid, point-of-care hrHPV DNA testing, unaided visual inspection after acetic acid (VIA), and “deep learning”-derived, automated visual evaluation (AVE) algorithm applied to a digital image captured on a cell phone, thereby ensuring that most CIN2/3 in the population is identified and treated. Screen-positive (HPV, VIA, 6-mo AVE positive) women will be 1) randomly assigned to either the GBC or thermocoagulation, 2) undergo a rigorous colposcopic evaluation and biopsies to determine the (post-hoc) diagnosis of the cervical abnormality, and 3) undergo their assigned treatment if ablation eligibility or LEEP if ineligible based on WHO guidelines8. Adverse events and pain data will be collected systematically during the treatment visit and during an at-home, one month post-treatment visit by community health workers. Six- and 18-month follow-up visits will be used to assess effectiveness of these treatments against CIN2/3 and hrHPV. Nested studies will evaluate whether 1) specific HPV genotypes, CD4 and HIV viral load, and/or lesion size, location, and severity (i.e. imperfect adherence to WHO guidelines), are risk factors for treatment failures by each method and 2) deep-learning algorithms applied to digital images can predict ablative treatment failures and thereby used in the future to triage screen-positive women to LEEP instead of ablation and thereby potentially be avoided those treatment failures. Secondary analyses will assess the effectiveness of 12 different S&T strategies based on different combinations of 6 screening methods (hrHPV with no triage, hrHPV with triage using HPV genotype groups, hrHPV with VIA triage, hrHPV with AVE triage, VIA alone, or AVE alone) and two ablative methods.

浸润性宫颈癌是女性第四大常见癌症，也是导致癌症相关死亡的原因。 全世界。低收入和中等收入国家(LMIC)经历了全球近90%的宫颈癌 负担，撒哈拉以南非洲(SSA)的宫颈癌发病率最高。人类 免疫缺陷病毒(HIV)感染对SSA的影响也不成比例，极大地增加了 宫颈癌。世界卫生组织现在发出了消除宫颈癌的行动呼吁， 这包括为青少年接种人乳头瘤病毒(HPV)疫苗，HPV是导致 宫颈癌，筛查中年妇女，以便及早发现和治疗宫颈异常 在变得癌症之前。然而，这两种治疗宫颈异常的最佳策略都是 来自SSA的艾滋病毒(WLWH)以及如何减少治疗失败尚不清楚。为了解决这一知识差距，我们 提出一项随机临床试验，以评估两种消融治疗方法的治疗效果， 气基冷冻和热凝治疗WLWH妇女CIN2/3和高危HPV。 符合条件的、经确认的世界卫生组织妇女(n=5,014)，年龄25-49岁，居住在莫桑比克马普托 与当地的总统艾滋病紧急救援计划(PEPFAR)一起，将被招募到 在参加他们例行的艾滋病毒护理探视时参加这项试验。同意的WLWH将由RAPID， 护理点hrHPV DNA检测，醋酸(VIA)后的无辅助目视检查，以及由深度学习衍生的， 自动视觉评估(AVE)算法应用于在手机上捕获的数字图像，从而 确保人口中的大多数CIN2/3得到识别和治疗。屏幕阳性(HPV、VIA、6个月平均 阳性)妇女将被随机分配到GBC或热凝组，2)接受严格的 镜评估和活检以确定宫颈异常的(后)诊断，以及3) 根据世卫组织指南8，如果符合消融资格，则接受分配的治疗；如果不符合，则接受LEEP治疗。不利的 事件和疼痛数据将在治疗访问期间和一个月的在家期间系统地收集 社区卫生工作者的治疗后访视。将使用为期6个月和18个月的随访访问来评估 这些治疗方法对CIN2/3和hrHPV的疗效。嵌套研究将评估1)特定的 HPV基因型别、CD4和HIV病毒载量和/或病变大小、位置和严重程度(即未完全遵守 世卫组织指南)，是每种方法治疗失败的风险因素和2)应用的深度学习算法 TO数字图像可以预测消融治疗失败，从而在未来用于筛查阳性 妇女接受LEEP而不是消融，从而有可能避免这些治疗失败。次要的 分析将基于6种不同的组合来评估12种不同的S战略的有效性 筛查方法(hrHPV没有分流，hrHPV使用HPV基因型组进行分流，hrHPV通过分流， HrHPV采用AVE分流、单独VIVE或单独AVE)和两种消融方法。