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生活在莫桑比克的艾滋病毒妇女降低宫颈癌风险的有效性

• 批准号: 9927140
• 负责人: PHILIP E CASTLE
• 金额: $ 15.11万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 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 2020-07-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927140
• 关键词: Ablation; Acetic Acids; Acquired Immunodeficiency Syndrome; Address; Adherence; Adolescent; Adoption; Adult; Adverse event; Affect; Africa South of the Sahara; Aftercare; Age; Algorithms; Biopsy; Cancer Burden; Cancer Etiology; Cancerous; Carbon Dioxide; Caring; Cellular Phone; Cervical; Cervical Cancer Screening; Cervical Intraepithelial Neoplasia; Cervical dysplasia; Cervix Uteri; Cessation of life; Cold Therapy; Community Health Aides; Consent; DNA; Data; Devices; Diagnosis; Early Diagnosis; Early treatment; Effectiveness; Electricity; Electrocoagulation; Eligibility Determination; Emergency Situation; Ensure; Evaluation; Excision; Freezing; Future; Gases; Generations; Genotype; Goals; Guidelines; HIV; HIV Seronegativity; HIV diagnosis; HPV-High Risk; Hand; Health Priorities; Home environment; Human Papilloma Virus Vaccination; Human Papillomavirus; Human papilloma virus infection; Knowledge; Lesion; Local anesthesia; Location; Malignant neoplasm of cervix uteri; Medical; Meta-Analysis; Methods; Morbidity - disease rate; Mozambique; Necrosis; Nitric Oxide; Pain; Population; Positioning Attribute; Prevalence; Prevention strategy; Randomized; Randomized Clinical Trials; Recommendation; Recurrence; Resources; Risk; Risk Factors; Risk Reduction; Safety; Screening Result; Serious Adverse Event; Severities; Speculums; Technical Expertise; Technology; Testing; Time; Tissues; Topical application; Treatment Effectiveness; Treatment Failure; Triage; Vaccination; Viral; Viral Load result; Virus Diseases; Visit; Visual; Woman; Work; World Health Organization; alternative treatment; automated visual evaluation; base; cancer risk; cervical cancer prevention; cohort; comparative effectiveness; compare effectiveness; deep learning; deep learning algorithm; digital; digital imaging; effective therapy; experience; follow-up; global health; health training; light weight; loop electrosurgical excision procedure; low and middle-income countries; mortality; point of care; portability; premalignant; prevent; programs; recruit; screening; secondary analysis; standard care; standard of care; treatment comparison; virtual

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.

侵入性宫颈癌是女性第四大常见的癌症，是癌症相关死亡率的原因 全世界。低收入和中等收入国家（LMIC）几乎经历了全球宫颈癌的90％ 负担，撒哈拉以南非洲（SSA）的宫颈癌发生率最高。人类 免疫缺陷病毒（HIV）感染也对SSA产生了不成比例的影响，大大增加了患有SSA的风险 宫颈癌。世界卫生组织现在有一个呼吁采取措施，以消除宫颈癌， 其中包括疫苗接种年轻的青少年针对人乳头瘤病毒（HPV）的疫苗接种，这是专业的病毒原因 宫颈癌，并筛查中学妇女的早期发现和治疗宫颈异常 在取消之前。但是，这是治疗与妇女的宫颈异常的最佳策略 来自SSA的艾滋病毒（WLWH）以及如何减轻治疗失败是未知的。为了解决知识中的这一差距，我们 建议一项随机临床试验，以评估两种消融治疗方法的治疗有效性， 基于气体的冷冻疗法和热凝，用于WLWH女性的CIN2/3和高危HPV的治疗。 符合条件，确认了25-49岁的WLWH妇女（n = 5,014），居住在莫桑比克的马普托 与当地的PEPFAR（总统的艾滋病紧急计划）计划的联系将被招募到 参加常规的艾滋病毒治疗访问时参加此试验。同意WLWH将由Rapid筛选 护理点HRHPV DNA测试，乙酸后无辅助的视觉检查（VIA）和“深度学习”衍生， 自动视觉评估（AVE）算法应用于手机上捕获的数字图像，从而 确保确定和处理大多数CIN2/3。屏幕阳性（HPV，Via，6-Mo Ave 阳性）妇女将为1）随机分配给GBC或热凝，2）严格 阴道镜评估和活检以确定（事后）宫颈异常的诊断，3） 如果基于WHO指南8，则在没有资格的情况下进行消融资格或LEEP进行分配的治疗。8。不利 事件和疼痛数据将在治疗访问期间和在家，一个月内系统地收集 社区卫生工作者的治疗后访问。六个月和18个月的随访将用于评估 这些处理对CIN2/3和HRHPV的有效性。嵌套研究将评估1）是否具体 HPV基因型，CD4和HIV病毒负荷以及/或病变的大小，位置和严重程度（即不完善的遵守 WHO指南），是每种方法的治疗失败的危险因素，2）应用深度学习算法 数字图像可以预测消融治疗失败，从而将来用于分类屏幕阳性 妇女要进行的而不是消融，从而避免了这些治疗失败。次要 分析将根据6种不同组合评估12种不同的S＆T策略的有效性 筛选方法（没有分类的HRHPV，使用HPV基因型组的Triage的HRHPV，HRHPV，via Triage， 具有AVE分类的HRHPV，单独或单独通过AVE）和两种消融方法。