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: 10490357
• 负责人: Kathleen Schmeler
• 金额: $ 63.01万
• 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 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490357
• 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; 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; Nitric Oxide; Pain; Population; Positioning Attribute; Prevalence; Prevention strategy; Randomized; Randomized Clinical Trials; Rapid screening; Recommendation; Recurrence; Resources; Risk; Risk Factors; Risk Reduction; 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; comparative safety; compare effectiveness; deep learning; deep learning algorithm; digital; digital imaging; effective therapy; effectiveness evaluation; experience; follow-up; global health; health training; light weight; loop electrosurgical excision procedure; low and middle-income countries; mortality; necrotic tissue; 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.

浸润性宫颈癌是女性中第四大常见癌症和癌症相关死亡原因 国际吧低收入和中等收入国家（LMIC）经历了全球近90%的宫颈癌 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（艾滋病毒）感染，这也不成比例地影响SSA，大大增加了风险， 宫颈癌世界卫生组织现在呼吁采取行动消除宫颈癌， 其中包括对青少年接种人乳头瘤病毒（HPV）疫苗， 子宫颈癌，以及对中年妇女进行筛查，以早期发现和治疗子宫颈异常 在癌变之前。然而，治疗患有宫颈癌的妇女宫颈异常的最佳策略 艾滋病毒（WLWH）从SSA和如何减轻治疗失败是未知的。为了填补这一知识空白，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， 基于气体的冷冻疗法和热凝，用于治疗WLWH女性中的CIN 2/3和高危HPV。 年龄在25-49岁，居住在莫桑比克马普托的符合条件的、经确认的WLWH妇女（n= 5 014）， 与当地的PEPFAR（总统艾滋病紧急救援计划）计划相结合，将招募 在参加常规HIV护理访视时参加本试验。将通过快速， 即时hrHPV DNA检测，乙酸后的独立目视检查（VIA），以及“深度学习”衍生， 自动视觉评估（AVE）算法应用于在蜂窝电话上捕获的数字图像，从而 确保人群中的大多数CIN 2/3得到识别和治疗。筛查阳性（HPV、VIA、6个月AVE 阳性）女性将1）随机分配至GBC或热凝，2）接受严格的 阴道镜评估和活检以确定宫颈异常的（事后）诊断，以及3） 根据WHO指南，如果符合消融资格，则接受分配的治疗，如果不符合条件，则接受LEEP治疗8。不良 将在治疗访视期间和一个月的居家期间系统收集事件和疼痛数据 社区卫生工作者的治疗后访问。6个月和18个月随访访视将用于评估 这些治疗对CIN 2/3和hrHPV的有效性。巢式研究将评价1）特异性 HPV基因型、CD 4和HIV病毒载量和/或病变大小、位置和严重程度（即，对 WHO指南）是每种方法治疗失败的风险因素，2）应用的深度学习算法 数字图像可以预测消融治疗失败，从而在未来用于筛选屏幕阳性 女性LEEP而不是消融，从而可能避免这些治疗失败。二次 分析将评估12种不同的科技战略的有效性，这些战略基于6种战略的不同组合 筛查方法（hrHPV无分诊，hrHPV分诊使用HPV基因型组，hrHPV分诊使用VIA分诊， hrHPV与AVE分诊、单独的VIA或单独的AVE）和两种消融方法。