Improving specificity of HPV Screen-and-Treat in South Africa

提高南非 HPV 筛查和治疗的特异性

基本信息

批准号：
8789475
负责人：
Louise Kuhn
金额：
$ 49.99万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-19 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8789475
关键词：
Address Adverse effects Africa South of the Sahara Age-Years Algorithms Bedside Testings Biological Assay Biological Markers Cancer Etiology Cervical Cervical Cancer Screening Cervix Neoplasms Cessation of life Clinical Research Collaborations Communities Computer software Country Cytology Data Detection Disease Effectiveness Engineering Enrollment Europe Genotype Government Grouping HIV Health Services Human Papillomavirus Human papilloma virus infection Human papillomavirus 16 Income International Malignant Neoplasms Malignant neoplasm of cervix uteri Messenger RNA Molecular Morbidity - disease rate Phase Point-of-Care Systems Population Predictive Value Public Health Resources Rural Safety Sampling South Africa Specificity Testing Time Triage Tuberculosis United States Public Health Service Universities Vagina Viral Load result Viral load measurement Visit Woman assay development base cancer prevention cervical cancer prevention clinical research site design improved instrument mortality novel point of care programs public health relevance screening success

项目摘要

DESCRIPTION (provided by applicant): The momentum to implement cervical cancer screening in low and middle income countries (LMIC) could be greatly enhanced if a robust point-of-care (POC) HPV test were available to utilize in the preferred "screen- and-treat (SAT)" approach. Furthermore, SAT programs could be made more attractive if HPV tests were modified, or additional tests added, to improve specificity of a single-round of screening without reducing sensitivity for the detection of cervical disease. This would reduce the magnitude of over-treatment without compromising the public health impact of the program. Our group at Columbia University has a well- established collaboration with the University of Cape Town, South Africa, with whom we have undertaken large clinical studies of cervical cancer prevention in low resource settings. We propose to partner with Cepheid, who have pioneered POC testing (GeneXpert) using self-contained real-time PCR cartridges and who are widely respected for their POC tests for tuberculosis that have become the global standard. Cepheid has recently developed a HPV POC test (Xpert HPV Assay) for use in Europe. We propose to re-engineer the Cepheid HPV test to make it more suitable for SAT in LMIC. The test will be re-engineered to improve specificity and positive predictive value (PPV) of HPV testing by: (1) utilizing differet cycle threshold (CT) cutoffs for different groupings of HPV genotypes, 2) investigating testing for only selected HPV genotypes and (3) investigating the potential of using quantitative HPV "viral load" measurements for HPV 16 and possibly other genotypes. To further address the challenge of over-treatment in the SAT approach, we propose to investigate the potential added value of tests for cellular mRNA cancer biomarkers. Cepheid has novel preliminary data demonstrating the utility of cellular mRNA biomarkers to distinguish high-grade cervical neoplasia. Some have already been formatted for the GeneXpert platform. These approaches are designed to improve the specificity and PPV of a single round of screening, and thereby reduce the number of women without cervical disease undergoing treatment, without seriously compromising sensitivity, so as to preserve the public health impact of a SAT program.

描述（由申请人提供）：如果可以在首选的“屏幕和水平（SAT）”方法中使用稳健的护理点（POC）HPV测试，则可以在低收入国家（LMIC）（LMIC）实施宫颈癌筛查（LMIC）的势头。此外，如果修改了HPV测试或添加了其他测试，则可以使SAT程序更具吸引力，以提高单轮筛查的特异性，而不会降低对宫颈疾病的敏感性的敏感性。这将减少过度治疗的程度，而不会损害该计划的公共卫生影响。我们在哥伦比亚大学的小组与南非开普敦大学建立了良好的合作，我们与他们在低资源环境中对宫颈癌预防进行了大型临床研究。我们建议与Cepheid合作，Cepheid使用独立的实时PCR弹药术进行了开创性的POC测试（GenExpert），并广受尊重的结核病测试已成为全球标准。 Cepheid最近开发了用于欧洲的HPV POC测试（XPERT HPV分析）。我们建议重新设计Cepheid HPV测试，以使其更适合在LMIC中进行SAT。该测试将经过重新设计，以提高HPV测试的特异性和正预测值（PPV）：（1）使用不同分组的HPV基因型分组利用不同的循环阈值（CT）截止，2）研究测试以研究测试以进行研究仅选择的HPV基因型和（3）研究对HPV 16和其他基因型使用定量HPV“病毒载荷”测量的潜力。为了进一步解决SAT方法中过度治疗的挑战，我们建议研究细胞mRNA癌症生物标志物测试的潜在附加值。 Cepheid具有新的初步数据，证明了细胞mRNA生物标志物区分高级宫颈肿瘤的实用性。一些已经为GenExpert平台格式化了。这些方法旨在提高一轮筛查的特异性和PPV，从而减少接受治疗的没有宫颈疾病的妇女的数量，而不会严重损害敏感性，从而保留SAT计划的公共卫生影响。