Point-of-Care Diagnostic Tools to Improve Global Cervical Cancer Control Programs

描述(申请人提供)：宫颈癌以前是美国女性癌症相关死亡的主要原因；然而，由于引入了检测早期宫颈癌及其先兆的筛查计划，发病率和死亡率下降了70%。与此形成鲜明对比的是，在低收入和中等收入国家(LMIC)，宫颈癌仍然是女性癌症死亡的第一或第二大原因。非常需要能够在资源有限的情况下使用的适当的宫颈癌筛查和诊断工具。世界卫生组织对低资源环境下宫颈癌预防方法的建议侧重于使用单独或联合使用醋酸(VIA)或HPV检测的目测检查进行筛查和治疗的策略。然而，在许多大型研究中，VIA和HPV检测的阳性预测价值被发现为10%。因此，仅根据VIA或HPV筛查，90%的检测结果呈阳性的女性将在诊疗环境中得到不适当的治疗。在这里，我们建议优化和验证高分辨率显微内窥镜(HRME)用于诊疗计划，以在不降低敏感性的情况下提高特异性。该应用程序的目标是优化和验证HRME的性能，以便在巴西的城市和农村环境中实时诊断宫颈癌。在UH2阶段，我们将展示HRME在一种新型移动诊断和治疗单元中的成功实施，以便在一次访问中实时诊断和治疗筛查阳性妇女的宫颈癌前病变，以减少失去随访的妇女数量。在UH3阶段，我们将开展一项涉及12,000多名女性的研究，以验证与VIA和阴道镜相比，HRME在一次就诊中结合诊断和治疗具有更高的诊断敏感性和特异性。我们的项目将验证HRME作为一种实时的活体诊断工具的使用，该工具可以作为阴道镜和活检等传统诊断方法的替代方案应用于各种情况，这些方法在许多LMICs中是不切实际的。我们的团队包括生物工程(莱斯大学)和宫颈癌预防和治疗(UT MD安德森癌症中心和巴雷托斯癌症医院)方面的专业知识。我们的团队已经合作了两年，以开发负担得起的、有效的技术，在低资源环境下预防宫颈癌。为了确保这项工作的成果在巴西国内外可持续实施和扩大规模，我们与全球子宫颈癌联盟合作，这是一个帮助LMICs实施全面、可持续和有效的子宫颈癌预防和控制的非政府组织。我们的发展合作伙伴是Becton Dickinson，这是一家跨国医疗技术公司，坚定地致力于全球改善妇女健康的努力。

DESCRIPTION (provided by applicant): Cervical cancer was previously the leading cause of cancer-related death among women in the US; however, incidence and mortality have decreased by >70% due to the introduction of screening programs to detect early cervical cancer and its precursors. In stark contrast, cervical cancer continues to be the 1st or 2nd leading cause of cancer death among women in low- and middle-income countries (LMICs). There is a significant need for appropriate cervical cancer screening and diagnostic tools that can be used in resource- limited settings. The World Health Organization's recommendations for cervical cancer prevention methods in low-resource settings focus on screen-and-treat strategies using visual inspection with acetic acid (VIA) or HPV testing, alone or in combination. However in many large studies, the positive predictive value of VIA and HPV testing have been found to be <10%. Thus, based on VIA or HPV screening alone, >90% of women with a positive test result would be inappropriately treated in a see-and-treat setting. Here, we propose to optimize and validate a high resolution microendoscope (HRME) to be used in see- and-treat programs to improve specificity without reducing sensitivity. The goal of this application is to optimize and validate the performance of the HRME for real-time diagnosis of cervical cancer in urban and rural settings in Brazil. In the UH2 phase, we will demonstrate successful implementation of the HRME in a novel mobile diagnostic and treatment unit for real-time diagnosis and treatment of cervical precancer in screen-positive women in a single visit in order to reduce the number of women lost to follow-up. In the UH3 phase, we will carry out a study involving over 12,000 women to validate that the HRME has improved diagnostic sensitivity and specificity compared to VIA and colposcopy for combined diagnosis and treatment in a single visit. Our project will validate the use of HRME as a real-time, in vivo diagnostic tool that can b applied in a variety of scenarios as an alternative to the traditional diagnostic methods of colposcopy and biopsy, which are impractical in many LMICs. Our team includes expertise in bioengineering (Rice University) and cervical cancer prevention and treatment (UT MD Anderson Cancer Center and Barretos Cancer Hospital). Our teams have worked together for two years to develop affordable, effective technologies for cervical cancer prevention in low-resource settings. To ensure that results of this work lead to sustainable implementation and scale-up within and beyond Brazil, we are teamed with the Global Coalition Against Cervical Cancer, an NGO that assists LMICs in the implementation of comprehensive, sustainable, and effective cervical cancer prevention and control. Our development partner is Becton Dickinson, a multi-national medical technology company with a strong commitment to global efforts to improve women's health.