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

描述(由申请人提供)：如果在首选的“筛查和治疗(SAT)”方法中可以利用强大的护理点(POC)HPV检测，那么在低收入和中等收入国家(LMIC)实施宫颈癌筛查的势头将大大增强。此外，如果修改HPV检测或增加额外的检测，在不降低检测宫颈疾病的敏感度的情况下，提高单轮筛查的特异性，SAT计划可能会变得更有吸引力。这将减少过度治疗的严重程度，而不会损害该计划对公共健康的影响。我们在哥伦比亚大学的团队与南非开普敦大学建立了良好的合作关系，我们与开普敦大学共同开展了在低资源环境下预防宫颈癌的大型临床研究。我们建议与Cepheid合作，Cepheid率先使用独立的实时PCR试剂盒进行POC检测(GeneXpert)，并因其结核病POC检测已成为全球标准而广受尊敬。造父变种最近开发了一种在欧洲使用的HPV POC检测(Xpert HPV Assay)。我们建议重新设计造父变种HPV测试，使其更适用于LMIC中的SAT。该检测将被重新设计，以提高HPV检测的特异性和阳性预测值(PPV)：(1)对不同的HPV基因型组使用不同的周期阈值(CT)界值；2)调查检测 仅限于选定的HPV基因类型；(3)研究使用定量HPV“病毒载量”测量HPV16和可能的其他基因类型的可能性。为了进一步解决SAT方法中过度治疗的挑战，我们建议调查细胞mRNA癌症生物标记物检测的潜在附加值。造父变种有新的初步数据，证明了细胞信使核糖核酸生物标记物在区分高级别宫颈肿瘤中的作用。其中一些已经针对GeneXpert平台进行了格式化。这些方法旨在提高单轮筛查的特异性和PPV，从而减少接受治疗的非宫颈疾病妇女的数量，而不会严重损害敏感性，从而保护SAT计划对公共健康的影响。

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.