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: 10246794
• 负责人: Karen Sue Anderson
• 金额: $ 82.34万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10246794
• 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; Electrical Engineering; Emerging Technologies; Engineering; Enzyme-Linked Immunosorbent Assay; Europe; Fingers; Funding; High grade dysplasia; Human Papilloma Virus Vaccine; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immune response; Immunoassay; Immunoglobulin G; India; Individual; Institutes; 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; SMART health; Sampling; Science; Screening for cancer; Sensitivity and Specificity; Serology; Serology test; Serum; Technology; Testing; Training; Triage; Underserved Population; United States National Institutes of Health; Validation; Viral; Visual; Woman; Work; antibody detection; antigen detection; biobank; biomarker development; biomarker panel; biomarker performance; cancer biomarkers; connected health; cost; cost effective; design; detection assay; detection limit; experience; global health; human disease; lateral flow assay; low and middle-income countries; malignant oropharynx neoplasm; mortality; multiplex assay; point of care; point-of-care detection; 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， 据估计，到2020年，宫颈癌将有超过20万例新发病例和超过10万例死亡 印度占全球病例的25%。子宫颈抹片检查及人类乳头瘤病毒检查 DNA检测已经成为美国和欧洲的标准护理，但过于昂贵和后勤 在低收入和中等收入国家（LMIC）。一种简单的床旁（POC）生物标志物面板， 高度不典型增生和宫颈癌可以提供一种具有成本效益的方法， 这些国家的HPV感染诱导系统性体液免疫应答与IgG抗体HPV- 衍生蛋白质。我们以前已经确定了一组五种HPV抗原的抗体， 88%的HPV+口咽癌患者，但不到4%的健康对照。使用经扩展的 在16种HPV抗原中，我们在45%的CIN II/III患者血清中检测到至少一种HPV抗体 发育不良这些结果支持开发一种快速、定量和多路复用的检测方法， 检测HPV相关的宫颈疾病。我们利用蛋白质微阵列技术， 荧光技术，使荧光，可编程，多重ELISA（血清学）检测HPV- 具有高分析灵敏度和快速， 定量输出。我们在这一领域的初步工作已经证明了HPV IgG抗体的检测 抗原的检测下限在10 pg/mL范围内，这是现有技术的100倍改进。 比色法根据我们提出的努力，我们的目标是开发和展示一个原型， 多重荧光可编程护理点检测，具有高分析灵敏度，可同时 从单个手指针刺大小的患者血液中检测16种HPV特异性IgG血清学生物标志物 可以以低于$1/患者样本的总试剂成本制造的样本。我们将利用我们 在微流体、电气工程、光学、生物标志物等方面拥有免疫分析开发方面的专业知识 分析和临床确认，以针对LMIC临床环境的器械和测定。我们还将 提供临床平台和生物储存库，以快速评估宫颈筛查的新兴技术。 该提案将调整工程和生物化学，以开发强大的POC装置， 针对中低收入国家的HPV血清学检测。我们会把这个 这项技术在印度筛查了13,000名患者，全印度医学研究所的一个合作者团队 印度，新德里，印度