Point of Care Diagnostics of HPV-Associated Cervical Cancer in HIV Epidemic Areas in China

摘要：人乳头瘤病毒(HPV)相关的宫颈癌是最常见的获得性宫颈癌之一。 免疫缺陷综合征(艾滋病)相关的恶性肿瘤。宫颈癌是全世界死亡率第二高的癌症。 全世界的妇女，目前已成为中国妇女健康的主要威胁，特别是在 中国农村和艾滋病流行区。高危类型的HPV是宫颈癌和 世卫组织建议将HPV检测用于低收入和中等收入国家的宫颈癌筛查 (LMIC)，如中国。然而，基于聚合酶链式反应的人乳头瘤病毒检测需要昂贵的聚合酶链式反应仪器，而且 在低成本集成电路中广泛使用是负担不起的。新近出现的基于核酸的CareHPVTM检测 杂交检测提供了相对更简单、更便宜和更便携的HPV检测，但 医疗点(PoC)诊断应用仍有许多缺点，包括：i)相对较长 检测时间(~3小时)，ii)由训练有素的技术人员使用，iii)依赖相对昂贵的仪器。在……里面 与中国医学科学院肿瘤研究所/医院的研究人员合作 (CICAMS)，我们建议开发、测试和验证一种低成本、最少仪器的POC诊断 HIV感染妇女中14种高危HPV基因和HIV病毒的快速检测系统 在中国的疫区。我们的POC诊断系统的独特之处在于：i)采用新的等温放大 多重分子诊断策略(即，HPV、HIV病毒)，ii)利用化学放热反应 为等温放大产生加热，使其运行不受电力影响，以及iii) 利用无处不在的移动电话技术记录、分析和报告结果，而无需 专门的光学探测器。我们提出了以下具体目标：i)PoC的发展和优化 诊断系统，ii)评估和验证其临床应用的可行性，以及iii)现场验证 以及德宏州等中国地区艾滋病流行地区POC系统可接受性评价， 云南省。这是美国PI与美国PIE之间的补充合作研究 护理点诊断技术，以及在宫颈癌筛查和现场领域拥有专业知识的中国PI- 测试。如果成功，这个项目将很容易转化为一种新的宫颈癌筛查护理点工具， 这在资源贫乏的环境下(即农村中国)将具有巨大的价值，使无数妇女受益。

Abstract: Human papillomavirus (HPV)-associated cervical cancer is one of the most common acquired immunodeficiency syndrome (AIDS)-related malignancies. Cervical cancer is the second deadliest cancer in women around the world, and has currently become a major threat to Chinese women's health, especially in rural China and HIV epidemic areas. High-risk types of HPV are the causative agents of cervical cancer and WHO has recommended HPV testing for cervical cancer screening in low- and middle-income countries (LMICs), such as China. However, PCR-based HPV detection requires expensive PCR instruments and is unaffordable for widespread use in LMICs. Recently emerging careHPVTM test, based on nucleic acid hybridization detection, has offered comparatively simpler, less expensive and more portable HPV testing, but still has many shortcomings for point-of-care (POC) diagnostic applications, including: i) relatively long detection time (~3 h), ii) use by well-trained technicians, and iii) reliance on relatively expensive instruments. In collaboration with investigators at the Cancer Institute/Hospital, Chinese Academy of Medical Sciences (CICAMS), we propose to develop, test, and validate a low-cost, minimally-instrumented POC diagnostic system for rapid detection of 14 individual high-risk HPV genotypes and HIV virus among women in HIV epidemic areas in China. Our POC diagnostic system is unique in: i) adapting a new isothermal amplification strategy for multiplex molecular diagnostics (i.e., HPV, HIV virus), ii) utilizing chemical exothermal reactions to produce the heating for isothermal amplification and freeing its operation from electrical power, and iii) leveraging ubiquitous mobile phone technology to record, analyze and report the results without the need for specialized optical detectors. We propose the following specific aims: i) development and optimization of POC diagnostic system, ii) evaluation and validation of its feasibility for clinical application, and iii) field validations and acceptability evaluation of POC system in HIV epidemic areas of China such as Dehong Prefecture, Yunnan Province. This is a complementary collaboration research between the U.S. PI with the experience on point-of-care diagnostic technology, and the Chinese PI with expertise on cervical cancer screening and field- testing. If successful, this project will readily translate into a new point-of-care tool for cervical cancer screening, which will be of tremendous value in resource poor settings (i.e., rural China) benefiting numerous women.