Cytology-Free POC Cervical Cancer Diagnostics for Global Health

 描述(申请人提供)：HPV相关宫颈癌是全球妇女死亡的主要原因之一，每年有500,000多例病例和275,000人死亡。虽然通过频繁使用巴氏涂片进行重复筛查大大降低了发达国家宫颈癌的发病率和死亡率，但绝大多数与宫颈癌相关的死亡发生在医疗保健基础设施最少的低收入和中等收入国家。事实证明，以细胞学为基础的预防方案在低资源环境下极难实施和维持，因此85%以上的宫颈癌新病例起源于发展中国家。传统的细胞学筛查缺乏足够的基础设施，加上宫颈癌的表现，直到癌症进入晚期才出现症状，这强调了临床上需要一种适合低资源环境的筛查测试。开发一种具有高灵敏度和高特异度的可靠的护理点(POC)测试能够降低全球宫颈癌的发病率和死亡率。我们建议开发一种新的基于纳米技术的诊断分析平台，以在低资源环境下检测宫颈癌进展。该多重分析平台目前正由Becton Dickinson(BD)开发用于非肿瘤学应用，其设计具有低成本、易使用和廉价的特点。我们建议调整这一平台，以开发一种高度特异性的诊断测试，该测试将筛查不需要治疗的妇女，并确定需要转诊为阴道镜检查的宫颈病变的妇女。这种诊断测试基于表面增强拉曼散射(SERS)技术，能够在不需要洗涤或纯化的情况下检测复杂样品中的多个目标。测试和分析在不到30分钟内完成，提供了“样本输入-答案输出”的工作流程，使该平台成为在低资源环境下进行“筛选和处理”测试的理想平台。诊断开发和验证将与拥有HPV和宫颈癌筛查以及临床肿瘤学专业知识的多学科团队密切合作进行。通过将BD在化验开发、全球医疗保健提供和监管批准方面的经验与其他团队成员的临床专业知识相结合，该团队拥有在低资源环境下开发和验证POC宫颈癌测试所需的专业知识。除了BD检测开发、工程设计、全球医疗服务和监管人员外，该团队还包括Jennifer S.Smith博士(北卡罗来纳大学教堂山分校)、Douglas Clark博士(UNM)、Mark Stoler博士(UVA Health System)、Scott McClelland博士(UW)，以及临床验证网站负责人包括乔友林博士(中国医学科学院)、Nelly Mugo博士(肯尼亚医学研究所)、Jose Fregnani博士(巴雷托斯癌症医院)和Adhemar Longatto-Filho博士(巴西巴雷托斯癌症医院)。

 DESCRIPTION (provided by applicant):HPV-associated cervical cancer is among the leading causes of death in women worldwide, with more 500,000 cases and 275,000 deaths annually. While repeated screening through frequent use of the Papanicolaou (Pap) smear has drastically reduced the incidence and mortality of cervical cancer in developed nations, the vast majority of cervical cancer-related deaths occur in low- and middle-income countries with minimal healthcare infrastructure. Cytology-based prevention programs have proven to be extremely difficult to implement and sustain in low-resource settings, and as a result over 85% of new cervical cancer cases originate in developing countries. The lack of adequate infrastructure for traditional cytology-based screening combined with the presentation of cervical cancer, where symptoms are not present until the cancer is in an advanced stage, emphasize the clinical need for a screening test appropriate for low resource settings. Development of a reliable Point-of-Care (POC) test with high sensitivity and specificity has the ability to reduce the incidence and mortality of cervical cancer worldwide. We propose to develop a novel nanotechnology- based diagnostic assay platform to detect cervical cancer progression in low-resource settings. This multiplex assay platform, which is currently being developed for non-oncology applications by Becton Dickinson (BD), is designed to be low-cost, easy to use, and inexpensive. We propose to adapt this platform to develop a highly specific diagnostic test that will screen women who do not need treatment and identify women with cervical lesions who need to be referred for colposcopy. The diagnostic test is based on Surfaced Enhanced Raman Scattering (SERS) technology, that enables detection of multiple targets in a complex sample without the need for washing or purification. The test and analysis is completed in less than 30 minutes, provides a "sample-in- answer-out" workflow, making the platform ideal for a "screen and treat" test in low-resource settings. Diagnostic development and validation will be done in close collaboration with a multidisciplinary team with expertise in HPV and cervical cancer screening as well as clinical oncology. By combining BD's experience in assay development, global healthcare delivery, and regulatory approval with the clinical expertise of other team members, the team has the expertise required to develop and validate a POC cervical cancer test for low resource settings. In addition to BD assay development, engineering, global healthcare delivery, and regulatory personnel, the team includes Dr. Jennifer S. Smith (UNC-Chapel Hill), Dr. Douglas Clark (UNM), Dr. Mark Stoler (UVA Health System), Dr. Scott McClelland (UW), and clinical validation site leaders including Dr. You-Lin Qiao (Chinese Academy of Medical Sciences), Dr. Nelly Mugo (Kenya Medical Research Institute), Dr. Jose Fregnani (Barretos Cancer Hospital), and Dr. Adhemar Longatto-Filho (Barretos Cancer Hospital, Brazil).