Cytology-Free POC Cervical Cancer Diagnostics for Global Health

无细胞学 POC 宫颈癌诊断促进全球健康

• 批准号: 9296093
• 负责人: JENNIFER SUSAN SMITH
• 金额: $ 49.1万
• 依托单位: BECTON, DICKINSON AND COMPANY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9296093
• 关键词: Academy; Antibodies; Antigens; Bedside Testings; Biological; Biological Assay; Blood; Brazil; Businesses; Cancer Detection; Cancer Diagnostics; Cancer Hospital; Cancer cell line; Cancerous; Cause of Death; Cervical; Cervical Cancer Screening; Cervical dysplasia; Cessation of life; China; Chinese People; Clinical; Clinical Oncology; Collaborations; Colposcopy; Complex; Country; Cytology; Detection; Developed Countries; Developing Countries; Development; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Engineering; Feces; Goals; Government; Health system; Healthcare; Human Papillomavirus; Human Resources; Immune response; Immunoassay; Incidence; Income; Kenya; Lesion; Location; Magnetism; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Medical; Medical Device; Medical Research; Nanotechnology; Neoplasms; Optics; Outcome; Pap smear; Performance; Preparation; Prevention program; Proteins; Reader; Reagent; Reporting; Research Infrastructure; Research Institute; Resources; Role; Running; Sampling; Science; Sensitivity and Specificity; Signal Transduction; Site; Specificity; Specimen; Surface; Swab; Symptoms; Technology; Testing; Time; Triage; Urine; Validation; Water; Woman; assay development; base; biomarker panel; clinical application; clinical research site; cost; design; diagnostic assay; experience; global health; health care delivery; improved; instrument; low and middle-income countries; member; mortality; multidisciplinary; multiplex detection; nanoparticle; novel; performance tests; point of care; point-of-care diagnostics; portability; programs; protein biomarkers; public health relevance; screening; targeted biomarker; tumor progression

 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).

 描述（由申请人提供）：HPV相关宫颈癌是全球女性死亡的主要原因之一，每年有超过500，000例病例和275，000例死亡。虽然通过频繁使用巴氏涂片（Pap）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，但绝大多数宫颈癌相关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。基于细胞学的预防计划已被证明在资源匮乏的环境中极难实施和维持，因此超过85%的新发宫颈癌病例起源于发展中国家。缺乏适当的基础设施进行传统的细胞学筛查，加上宫颈癌的表现，其中症状不存在，直到癌症处于晚期阶段，强调临床需要适合低资源环境的筛查测试。开发具有高灵敏度和特异性的可靠床旁（POC）检测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检测平台，以在低资源环境中检测宫颈癌进展。目前Becton Dickinson（BD）正在开发用于非肿瘤学应用的这种多重检测平台，其设计成本低，易于使用且价格低廉。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，该测试将筛选不需要治疗的妇女，并确定需要进行阴道镜检查的宫颈病变妇女。该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分钟的时间内完成，提供了“样品输入-回答”的工作流程，使该平台成为低资源环境下“筛选和治疗”测试的理想选择。诊断开发和验证将与一个在HPV和宫颈癌筛查以及临床肿瘤学方面具有专业知识的多学科团队密切合作。通过将BD在检测开发、全球医疗保健服务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，该团队拥有为低资源环境开发和验证POC宫颈癌检测所需的专业知识。除了BD检测开发、工程、全球医疗服务和监管人员外，该团队还包括Jennifer S. Smith博士（UNC-Chapel Hill）、道格拉斯克拉克博士（UNM）、Mark Stelland博士（UVA Health System）、Scott McClelland博士（UW）和临床验证中心负责人，包括You-Lin Qiao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（Barretos癌症医院）和Adhemar Longatto-Filho博士（Barretos癌症医院，巴西）。