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

描述（由申请人提供）：如果一种强大的即时护理（POC） HPV检测可用于首选的“筛查和治疗（SAT）”方法，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，如果对HPV检测进行修改，或增加额外的检测，以提高单轮筛查的特异性，而不降低检测宫颈疾病的敏感性，SAT项目可能会更具吸引力。这将减少过度治疗的规模，而不会损害该计划对公共卫生的影响。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关系，我们在低资源环境下进行了大规模的宫颈癌预防临床研究。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检测而受到广泛尊重，该检测已成为全球标准。造父变星公司最近开发了一种用于欧洲的HPV POC检测（Xpert HPV Assay）。我们建议重新设计造父变星HPV检测，使其更适合于LMIC的SAT。该测试将被重新设计，以提高HPV检测的特异性和阳性预测值（PPV）：(1)对不同的HPV基因型分组使用不同的周期阈值（CT）截止值

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.