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.

项目总结。尽管有效的人乳头瘤病毒（HPV）疫苗的发展，它一直