Point-of-care HPV mRNA test for cervical cancer screening in low-resource settings

在资源匮乏地区进行宫颈癌筛查的护理点 HPV mRNA 检测

基本信息

批准号：
10331882
负责人：
Rebecca R. Richards-Kortum
金额：
$ 18.19万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10331882
关键词：
Address Benign Biological Assay Biological Markers Biopsy Cancerous Cervical Cervical Cancer Screening Cessation of life Climate Clinical Clinical Sensitivity Collaborations Colposcopy Complex Consensus Country Cytology DNA Detection Development Devices Diagnosis Diagnostic Early Diagnosis Early treatment Electricity Epidemiology Equipment Future Goals HPV E7 HPV-High Risk Human Papilloma Virus Vaccination Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 Human papillomavirus 18 Incidence Industrialization Infrastructure Lateral Lesion Malignant Neoplasms Malignant neoplasm of cervix uteri Measures Medically Underserved Area Messenger RNA Methods Molecular Nucleic Acid Amplification Tests Nucleic Acids Oncoproteins Papillomavirus Transforming Protein E6 Patients Performance Point-of-Care Systems Population Preparation Prevention program Process Production Publications RNA Reagent Research Resource-limited setting Resources Risk Sampling Secondary Prevention Sensitivity and Specificity Specificity System Technology Temperature Test Result Testing Texas Transcript Translating Visual Woman accurate diagnosis amplification detection cancer care cancer invasiveness cervical cancer prevention cost cost effective design detection method early screening effectiveness testing experience follow-up improved innovation instrument instrumentation isothermal amplification laboratory equipment low and middle-income countries medically underserved mortality novel overtreatment point of care point of care testing point-of-care diagnostics premalignant prevent prospective prototype public health relevance randomized trial screening screening program standard of care stem viral DNA

项目摘要

Abstract: There is a significant need to improve global access to cervical cancer screening. Globally, approximately 570,000 women are diagnosed with and 311,000 women die from cervical cancer each year. Nearly 90 percent of cervical cancer deaths occur in low- and middle-income countries (LMICs), due mainly to challenges in implementing effective screening programs. Likewise, cervical cancer rates in medically underserved areas in the US remain high. For example, in the Rio Grande Valley of Texas, cervical cancer incidence rates are 55% higher than the US average, and approximately 10% of eligible women are screened. There is broad consensus that high-risk human papillomavirus (hrHPV) testing is the best approach to improve global screening efforts. An HPV biomarker that provides excellent sensitivity and better specificity than DNA is hrHPV mRNA. However, currently available hrHPV mRNA testing remains too complex and costly (e.g. >$45,000 for equipment and roughly $74 per test) for effective implementation into low-resource and medically underserved settings. Advances in isothermal amplification and lateral flow detection offer an opportunity to develop a point-of-care (POC) hrHPV mRNA test that is accurate, affordable, and can be performed in low-resource settings. The goal of this proposal is to combine isothermal amplification and lateral flow detection within an integrated point-of- care device to dramatically lower the cost of hrHPV mRNA testing. We will develop a low-cost, POC hrHPV E7 mRNA test that requires minimal laboratory equipment and performs as well as commercial RNA tests. Isothermal amplification reduces the instrumentation cost and complexity typically associated with nucleic acid amplification requiring only a single-temperature heater. Lateral flow detection integrates sample manipulation processes and wicks all detection reagents past pre-defined test zones, producing a simple, colorimetric readout. Our proposed proof-of-concept test will detect HPV types 16 and 18, the two types responsible for 70% of cervical cancer, and we estimate will cost <$3 per test in low-volume production. Consistent with the exploratory/developmental goals of an R21 proposal, we aim to (1) design and optimize HPV 16 and 18 E7 mRNA amplification assays and lateral flow detection; (2) combine mRNA amplification and detection into a single POC device; (3) evaluate performance of the developed mRNA test using synthetic and clinical samples. We will leverage the expertise of our interdisciplinary team, which includes designing technologies for LMICs, cervical cancer care, HPV diagnostics, and epidemiology, to develop, validate, and translate this novel screening test. We intend to build from this proof-of-concept test to incorporate HPV mRNA detection for types 31,33, 35, 45, 52, and 58 in the future to achieve detection of the HPV types that cause >90% of cervical cancer. Collectively, this research will lead to the development and implementation of a scalable, cost- effective screening test, a critical and necessary step toward the global elimination of cervical cancer.

抽象的：非常需要改善全球对宫颈癌筛查的机会。大约在全球每年有57万名妇女被诊断出患有宫颈癌，311,000名妇女死亡。将近90％宫颈癌死亡发生在低收入和中等收入国家（LMIC），这主要是由于挑战实施有效的筛选计划。同样，在医学匮乏地区的宫颈癌发生率美国仍然很高。例如，在德克萨斯州的里奥格兰德谷（Rio Grande Valley）中，宫颈癌的发病率为55％筛选高于美国的平均水平，约有10％的合格妇女被筛选。有广泛的共识高风险的人乳头瘤病毒（HRHPV）测试是改善全球筛查工作的最佳方法。一个与DNA相比，HPV生物标志物具有出色的灵敏度和更好的特异性是HRHPV mRNA。然而，目前可用的HRHPV mRNA测试仍然太复杂且昂贵（例如，设备和45,000美元每次测试约74美元）有效实施低资源和医疗服务不足的设置。等热放大和横向流动检测的进步提供了一个机会来开发护理点（POC）精确，负担得起的HRHPV mRNA测试，可以在低资源设置中进行。目标该建议的是将等温扩增和横向流动检测结合在综合点护理设备可大大降低HRHPV mRNA测试的成本。我们将开发低成本的POC HRHPV E7 MRNA测试需要最少的实验室设备并执行商业RNA测试。等温扩增可降低仪器成本和通常与核酸相关的复杂性放大只需要单个温度加热器。侧流检测整合样品操作流程和焊缝所有检测试剂都超过了预定义的测试区，从而产生了简单的比色读数。我们提出的概念验证测试将检测HPV类型16和18，这两种造成70％的宫颈的类型癌症，我们估计在低量生产中，每次测试的费用<$ 3。与R21提案的探索性/发展目标一致，我们的目标是（1）设计和优化HPV 16和18 E7 mRNA扩增测定和横向流动检测；（2）结合mRNA扩增和检测到单个POC设备；（3）使用合成和临床样品。我们将利用跨学科团队的专业知识，包括设计 LMIC，宫颈癌护理，HPV诊断和流行病学的技术，用于发展，验证和翻译这种新颖的筛选测试。我们打算通过此概念验证测试构建以纳入HPV mRNA 未来的31,33、35、45、52和58类型的检测以实现导致> 90％的HPV类型的检测宫颈癌。总的来说，这项研究将导致开发和实施可扩展的，成本 - 有效的筛查测试，这是朝着全球消除宫颈癌的关键和必要的步骤。