Rapid Point of Care Detection of HPV-Associated Malignancies

HPV 相关恶性肿瘤的快速护理点检测

• 批准号: 9933545
• 负责人: Karen Sue Anderson
• 金额: $ 77.9万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-12 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9933545
• 关键词: Acetic Acids; Anogenital cancer; Antibodies; Antigens; Area; Biochemistry; Biological Assay; Biological Markers; Blood; Blood specimen; Cancer Center; Cancer Detection; Caring; Cervical; Cervical Cancer Screening; Cervical dysplasia; Cervix Uteri; Cessation of life; Clinical; Country; DNA; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Dysplasia; Electrical Engineering; Emerging Technologies; Engineering; Enzyme-Linked Immunosorbent Assay; Europe; Fingers; Funding; Health; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune response; Immunoassay; Immunoglobulin G; India; Individual; Institutes; Lateral; Logistics; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Medical; Microarray Analysis; Microfluidics; Optics; Output; Pap smear; Patients; Performance; Phase; Pilot Projects; Predictive Value; Protein Array; Protein Microchips; Proteins; Proteome; Publications; Quality Control; Reagent; Resources; Risk; Sampling; Science; Screening for cancer; Sensitivity and Specificity; Serologic tests; Serological; Serum; Technology; Testing; Training; Triage; Underserved Population; United States National Institutes of Health; Validation; Viral; Visual; Woman; Work; biobank; biomarker development; biomarker panel; biomarker performance; cancer biomarkers; cost; cost effective; design; experience; global health; human disease; low and middle-income countries; malignant oropharynx neoplasm; mortality; point of care; portability; programs; prospective; prototype; response; screening; standard of care

Project Summary. Despite the development of effective human papillomavirus (HPV) vaccines, it has been estimated that there will be over 200,000 new cases and over 100,000 deaths due to cervical cancer by 2020 in India, which has 25% of the global burden of cases. Cervical cancer screening by Pap smears and HPV DNA testing has become standard of care in the US and Europe, but has been too expensive and logistically challenging in low and middle income countries (LMICs). A simple, point-of-care (POC) biomarker panel for high-grade dysplasia and cervical cancer could provide a cost-effective means for triage of cervical disease in these countries. HPV infection induces systemic humoral immune responses with IgG antibodies to HPV- derived proteins. We have previously identified antibodies to a panel of five HPV antigens that detect up to 88% of patients with HPV+ oropharyngeal cancer, but less than 4% of healthy controls. Using an expanded panel of 16 HPV antigens, we have detected at least one HPV antibody in the sera of 45% of CIN II/III cervical dysplasia. These results support the development of a rapid, quantitative, and multiplexed assay for the detection of HPV-related cervical disease. We leverage our protein microarray technology with advances in fluorescent technologies to enable a fluorescent, programmable, multiplexed ELISA (serologic) assay for HPV- specific IgG antibodies in a compact and disposable configuration with high analytic sensitivity and rapid, quantitative output. Our preliminary work in this area has demonstrated detection of IgG antibodies to HPV antigens with lower limits of detection in the 10pg/mL range, which is a 100-fold improvement over existing colorimetric approaches. Under our proposed effort, we aim to develop and demonstrate a prototype multiplexed fluorescent programmable point-of-care assay with high analytical sensitivity for the simultaneous detection of 16 individual HPV-specific IgG serologic biomarkers from a single finger stick-sized patient blood sample which can be manufactured for a total reagent cost of less than $1/patient sample. We will leverage our expertise in immunoassay development with expertise in microfluidics, electrical engineering, optics, biomarker analytical and clinical validation to target the device and assays for the LMIC clinical setting. We will also provide a clinical platform and biorepository to rapidly evaluate emerging technologies for cervical screening. This proposal will adapt the engineering and biochemistry for the development of robust POC devices for detection of HPV serology specifically for low and middle-income countries. We will transfer and evaluate this technology, screening 13,000 patients in India, with a team of collaborators in the All India Institute of Medical Sciences (AIIMS) in New Delhi, India.

项目摘要。尽管开发了有效的人乳头瘤病毒（HPV）疫苗，但它一直是 估计到2020 在印度，有25％的全球案件负担。子宫颈抹片检查和HPV筛查宫颈癌筛查 DNA测试已成为美国和欧洲的护理标准，但在逻辑上太昂贵了 在低收入国家（LMIC）中具有挑战性。一个简单的护理（POC）生物标志物面板 高级发育不良和宫颈癌可以为宫颈疾病中的宫颈疾病提供一种经济有效的手段 这些国家。 HPV感染可诱导全身性体液免疫反应，其IgG抗体对HPV- 衍生的蛋白质。我们以前已经鉴定出对五个HPV抗原的面板的抗体，该抗原检测到 HPV+口咽癌患者中有88％，但不到4％的健康对照。使用扩展 16 HPV抗原的面板，我们在CIN II/III宫颈45％的血清中至少检测到一种HPV抗体 发育不良。这些结果支持开发快速，定量和多路复用测定法 检测与HPV相关的宫颈疾病。我们利用蛋白质微阵列技术的进步 荧光技术可实现HPV-的荧光，可编程，多重ELISA（血清学）测定 紧凑型和一次性构型中的特定IgG抗体具有高度分析敏感性和快速， 定量输出。我们在该领域的初步工作表明了对HPV的IgG抗体的检测 抗原在10pg/mL范围内具有下限的抗原，这比现有的100倍改善 比色方法。在我们提出的努力下，我们旨在开发和展示原型 多路复用荧光可编程的护理点测定，对同时的分析灵敏度高 从单手指大小的患者血液中检测16个单独的HPV特异性IgG血清学生物标志物 样品可以以总试剂成本低于$ 1/患者样本制造。我们将利用我们的 免疫测定开发方面的专业知识，具有微流体，电气工程，光学，生物标志物方面的专业知识 分析和临床验证以针对该设备和LMIC临床环境的测定法。我们也会 提供临床平台和生物座席，以快速评估新兴技术进行宫颈筛查。 该建议将适应工程和生物化学的开发，以开发可靠的POC设备 专门针对低收入和中等收入国家的HPV血清学检测。我们将转移和评估 技术，在印度筛查13,000名患者，并与全印度医学研究所的一组合作者团队 印度新德里的科学（AIIMS）。