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 免疫缺陷综合征（AIDS）相关的恶性肿瘤。宫颈癌是世界上第二大致命癌症。 世界各地的妇女，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地区。高危型HPV是宫颈癌的病原体， 世卫组织建议在低收入和中等收入国家进行HPV检测用于宫颈癌筛查 （LMIC），如中国。然而，基于PCR的HPV检测需要昂贵的PCR仪器， 无法在中低收入国家广泛使用。最近出现的careHPVTM检测，基于核酸 杂交检测提供了相对更简单、更便宜和更便携的HPV检测，但 但是对于护理点（POC）诊断应用仍然具有许多缺点，包括：i）相对长的 检测时间（约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 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，最小仪器化的POC诊断 HIV感染妇女中14种高危HPV基因型和HIV病毒快速检测系统 中国的流行区。我们的POC诊断系统在以下方面是独一无二的：i）采用新的等温扩增 用于多重分子诊断的策略（即，HPV，HIV病毒），ii）利用化学外显反应， 产生用于等温扩增的加热并使其操作免于电力，以及iii） 利用无处不在的移动的电话技术来记录、分析和报告结果， 专门的光学探测器。我们提出了以下具体目标：i）开发和优化POC 诊断系统，ii）临床应用可行性的评价和验证，以及iii）现场验证 以及POC系统在中国德宏州等HIV流行区的可接受性评价， 云南省这是一个互补的合作研究之间的美国PI的经验， 床旁诊断技术，以及具有宫颈癌筛查和现场专业知识的中国PI- 试验.如果成功，该项目将很容易转化为宫颈癌筛查的新的护理点工具， 这在资源贫乏的环境中将具有巨大的价值（即，中国农村），惠及众多妇女。

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.