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

• 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
• 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

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 尽管宫颈癌如果及早发现是一种很容易治愈的疾病，但它仍在夺走许多人的生命 全世界有成千上万的女性。医疗保健差距导致了宫颈癌的发病率 低收入和中等收入国家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 对口单位。宫颈癌发病率和死亡率的巨大差异归因于较高的HPV 感染率和缺乏可获得的宫颈侵袭前病变的筛查和治疗。 美国目前的护理标准是基于细胞学的巴氏涂片，需要资源密集型实验室 和临床专家，从样本收集到结果需要很长的周转时间。可选方案，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，领先 过度治疗可能导致包括不孕不育和早产在内的并发症，并进一步加重负担 有限的医疗资源。该提案旨在创建一种综合的护理点筛查测试，该测试可以 在资源不足的情况下由医疗保健提供者使用，以获得相关的临床见解，包括宫颈 癌症风险分层，并实现高危宫颈病变的同一就诊治疗。 在我们初步开发的高灵敏度纸基免疫分析的基础上，测试关键 宫颈癌生物标记物，含有Valosin的蛋白(VCP)，本提案的目的是结合VCP 与其他三个已知的宫颈癌蛋白生物标志物一起检测，在一个敏感和特定的单步点- Of-Care分析。 具体里程碑包括： 1)将宫颈癌生物标志物的多重检测集成和优化到简单的纸质基础上 样本到答案的设备。 2)在回溯性宫颈拭子样本中评估检测的操作和性能指标。 这项提议的结果将是一项具有高度特征性的、具有高敏感性(95%)和 检测高危宫颈上皮内瘤变和浸润性宫颈癌的特异度(90%)在40 几分钟。这一负担得起的宫颈癌筛查和控制程序解决方案将适用于LMIC 并将在美国提供对宫颈上皮内瘤变的高度敏感的监测，它将在那里 尤其是对目前未得到现有筛查计划服务的高危人群。