Point-of-care screening test for early cervical cancer detection

用于早期宫颈癌检测的护理点筛查测试

基本信息

批准号：
10650144
负责人：
Jacqueline Linnes
金额：
$ 40.54万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-22 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10650144
关键词：
Acetic Acids Antibodies Area Binding Biological Assay Biological Markers Biomedical Engineering Blinded Buffers CDKN2A gene Cancerous Caring Cause of Death Cell Culture Techniques Cervical Cervical Cancer Screening Cervical Intraepithelial Neoplasia Cessation of life Characteristics Clinical Cold Therapy Country Cytology Cytolysis Detection Development Devices Diagnostic Disease Disease Progression Disparity Early Diagnosis Ensure Enzyme-Linked Immunosorbent Assay Evaluation Flowers Goals Gynecologic Oncologist Health Personnel Healthcare Horseradish Peroxidase Human Papilloma Virus Vaccination Human Papillomavirus Human Resources Human papilloma virus infection Immunoassay Incidence Income Infertility Infrastructure Laboratories Lesion MCM2 gene Malignant Neoplasms Malignant neoplasm of cervix uteri Marketing Methods Monitor North Carolina Outcome Pap smear Paper Pathologist Patients Performance Policies Predictive Value Premature Birth Prevention Primary Prevention Process Proteins Rapid screening Rare Diseases Reagent Receiver Operating Characteristics Refrigeration Resource-limited setting Resources Risk Reduction Rural Sampling Scientist Screening procedure Sensitivity and Specificity Signal Transduction Specialist Specificity Specimen Step Tests Swab TOP2A gene Techniques Technology Testing Time United States Universities Vaccines Visit Visual Woman World Health Organization Zambia beta Actin cancer biomarkers cancer health disparity cancer invasiveness clinical infrastructure clinically relevant early screening follow-up health care availability health care delivery health care disparity high risk high risk population infection rate insight instrumentation low and middle-income countries mortality multiplex detection nanoGold overtreatment performance tests point of care point of care testing premalignant programs protein biomarkers protein purification risk stratification rural America sample collection scale up screening screening program skills standard of care tumor progression two-dimensional valosin-containing protein viral detection

项目摘要

SUMMARY ABSTRACT Although cervical cancer is an easily curable disease if detected early, it continues to claim the lives of hundreds of thousands of women worldwide. Healthcare disparities have resulted in cervical cancer incidence and mortality that are five times higher in low and middle income countries (LMICs) than in high-income countries. In the United States, cervical cancer mortality rates are twice as high among rural women than their urban counterparts. The wide disparity in cervical cancer incidence rates and deaths is attributed to both higher HPV infection rates and a lack of accessible screening and treatment of pre-invasive cervical lesions. The current standard of care in the US, a cytology-based Pap smear, requires resource intensive laboratory and clinical specialists with a long turnaround time from sample collection to result. Alternatives, such as visual inspection with acetic acid and emerging HPV-targeted tests, have poor specificity for cervical cancer, leading to overtreatment that can cause complications including infertility and pre-term births and that further the burden on limited healthcare resources. This proposal aims to create an integrated point-of-care screening test that can be used by healthcare providers in under-resourced settings to obtain relevant clinical insights, including cervical cancer risk stratification, and enable same-visit treatment of high risk cervical lesions. Building on our preliminary development of a highly sensitive paper-based immunoassay to test for the key cervical cancer biomarker, valosin containing protein (VCP), the objective of this proposal is to combine VCP detection with three other known cervical cancer protein biomarkers, in a sensitive and specific single-step point- of-care assay. Specific milestones include: 1) Integrating and optimizing multiplex detection of cervical cancer biomarkers into a simple paper-based sample-to-answer device. 2) Evaluating the operational and performance metrics of the test in retrospective cervical swab samples. The outcome of this proposal will be a highly characterized point-of-care test with high sensitivity (95%) and specificity (90%) to detect high-risk cervical intraepithelial neoplasia and invasive cervical cancer within 40 minutes. This affordable solution for cervical cancer screening and control programs will be applicable in LMICs and will provide highly sensitive monitoring of cervical intraepithelial neoplasia in the US, where it will be especially impactful in high-risk populations that are currently underserved by existing screening programs.

摘要摘要尽管宫颈癌是一种如果及早发现就很容易治愈的疾病，但它仍然夺去了许多人的生命。全世界有数十万女性。医疗保健差异导致宫颈癌发病率低收入和中等收入国家 (LMIC) 的死亡率是高收入国家的五倍。在美国，农村妇女的宫颈癌死亡率是城市妇女的两倍同行。宫颈癌发病率和死亡率的巨大差异归因于较高的 HPV 感染率高以及缺乏对浸润前宫颈病变的筛查和治疗。美国当前的护理标准是基于细胞学的子宫颈抹片检查，需要资源密集型实验室从样本采集到结果的周转时间较长的临床专家。替代方案，例如视觉醋酸检查和新兴的 HPV 靶向检测对宫颈癌的特异性较差，导致过度治疗可能导致不孕症和早产等并发症，并进一步加重负担在有限的医疗资源上。该提案旨在创建一个集成的护理点筛查测试，可以供资源贫乏地区的医疗保健提供者使用以获得相关的临床见解，包括宫颈癌癌症风险分层，并实现高危宫颈病变的同诊治疗。基于我们初步开发的高灵敏度纸基免疫测定法来测试关键宫颈癌生物标志物，valosin 含蛋白（VCP），本提案的目标是结合 VCP 与其他三种已知的宫颈癌蛋白质生物标志物一起检测，以敏感且特异的单步点进行检测护理检测。具体里程碑包括： 1) 将宫颈癌生物标志物的多重检测整合并优化为简单的纸质文件样本到答案设备。 2) 评估回顾性宫颈拭子样本中测试的操作和性能指标。该提案的结果将是一个高度特征化的护理点测试，具有高灵敏度 (95%) 和特异性 (90%) 检测 40 以内的高危宫颈上皮内瘤变和浸润性宫颈癌分钟。这种经济实惠的宫颈癌筛查和控制计划解决方案将适用于中低收入国家并将在美国提供对宫颈上皮内瘤变的高度敏感监测，对目前现有筛查计划服务不足的高危人群尤其有影响力。