Rapid Point of Care Detection of HPV-Associated Malignancies

HPV 相关恶性肿瘤的快速护理点检测

基本信息

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
项目类别：
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

项目摘要

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，但预计到2020年，宫颈癌新发病例将超过20万，死亡人数将超过10万印度的病例负担占全球的 25%。通过子宫颈抹片检查和 HPV 进行宫颈癌筛查 DNA 检测已成为美国和欧洲的护理标准，但成本过高且不方便低收入和中等收入国家 (LMIC) 面临挑战。一个简单的即时护理 (POC) 生物标志物组高度不典型增生和宫颈癌可以为宫颈疾病的分诊提供具有成本效益的方法这些国家。 HPV 感染可诱导全身体液免疫反应，产生针对 HPV 的 IgG 抗体衍生蛋白质。我们之前已经鉴定出针对一组五种 HPV 抗原的抗体，可检测最多 88% 的患者患有 HPV+ 口咽癌，但低于健康对照的 4%。使用扩展的 16种HPV抗原，我们在45%的CIN II/III宫颈癌患者的血清中检测到至少一种HPV抗体发育不良。这些结果支持快速、定量和多重检测的开发 HPV相关宫颈疾病的检测。我们利用我们的蛋白质微阵列技术和先进技术荧光技术可实现 HPV 荧光、可编程、多重 ELISA（血清学）检测特异性 IgG 抗体采用紧凑且一次性的配置，具有高分析灵敏度和快速、定量输出。我们在该领域的前期工作已证明可检测 HPV IgG 抗体抗原检测限在 10pg/mL 范围内，比现有技术提高了 100 倍比色法。根据我们提议的努力，我们的目标是开发和演示一个原型多重荧光可编程即时检测，具有高分析灵敏度，可同时进行从指尖大小的患者血液中检测 16 种 HPV 特异性 IgG 血清学生物标志物样品的生产总试剂成本低于 1 美元/患者样品。我们将利用我们的免疫分析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针对 LMIC 临床环境的设备和检测进行分析和临床验证。我们还将提供临床平台和生物样本库，以快速评估新兴的宫颈筛查技术。该提案将调整工程和生物化学，以开发稳健的 POC 设备专门针对低收入和中等收入国家的 HPV 血清学检测。我们将对此进行转移和评估技术，与全印度医学研究所的合作者团队在印度筛查了 13,000 名患者印度新德里科学 (AIIMS)。