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

摘要 虽然子宫颈癌是一种容易治愈的疾病，如果早期发现，它继续夺去生命， 全世界成千上万的女性。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 感染率以及缺乏对浸润前宫颈病变的筛查和治疗。 美国目前的护理标准是基于细胞学的巴氏涂片检查，需要资源密集型实验室 和临床专家，从样本采集到结果的周转时间很长。替代方案，如视觉 醋酸检查和新出现的HPV靶向检测对宫颈癌的特异性较差， 过度治疗可能导致并发症，包括不孕症和早产， 有限的医疗资源。该提案旨在创建一种综合的即时筛查测试， 供医疗保健提供者在资源不足的环境中使用，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一次就诊治疗。 基于我们初步开发的一种高灵敏度的纸基免疫检测方法， 宫颈癌生物标志物，含Valosin蛋白（VCP），本提案的目的是将联合收割机VCP 检测与其他三个已知的宫颈癌蛋白质生物标志物，在一个敏感和特定的单步点- 护理测定。 具体里程碑包括： 1)整合和优化宫颈癌生物标志物的多重检测到一个简单的纸基 采样-应答装置 2)在回顾性宫颈拭子样本中评价检测的操作和性能指标。 该提案的结果将是一个高度特征化的床旁检测，具有高灵敏度（95%）， 特异性（90%）检测高危宫颈上皮内瘤变和浸润性宫颈癌在40 分钟这种负担得起的宫颈癌筛查和控制方案将适用于中低收入国家 并将在美国提供高度敏感的宫颈上皮内瘤变监测， 特别是对目前现有筛查项目服务不足的高危人群有影响。

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.