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

提高南非 HPV 筛查和治疗的特异性

• 批准号: 8929184
• 负责人: Louise Kuhn
• 金额: $ 49.82万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8929184
• 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; 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; screening; success

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）：如果能够在首选的“筛查和治疗（SAT）”方法中使用强大的护理点（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可能会大大增强。此外，如果修改 HPV 检测或添加额外的检测，以提高单轮筛查的特异性，同时又不降低宫颈疾病检测的敏感性，那么 SAT 计划可能会更具吸引力。这将减少过度治疗的程度，同时又不会影响该计划对公共卫生的影响。我们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，我们与该大学一起在资源匮乏的环境中开展了宫颈癌预防的大型临床研究。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受到广泛尊重。 Cepheid 最近开发了一种 HPV POC 检测（Xpert HPV Assay），供欧洲使用。我们建议重新设计 Cepheid HPV 检测，使其更适合中低收入国家的 SAT。该测试将被重新设计，以通过以下方式提高 HPV 测试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，2) 研究针对 仅选择选定的 HPV 基因型，并且 (3) 研究对 HPV 16 和可能的其他基因型使用定量 HPV“病毒载量”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 拥有新颖的初步数据，证明细胞 mRNA 生物标志物可用于区分高级别宫颈肿瘤。有些已经针对 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无宫颈疾病的女性数量，同时不会严重影响敏感性，从而保持 SAT 计划对公共健康的影响。

项目成果

Point-of-care testing with Xpert HPV for single-visit, screen-and-treat for cervical cancer prevention: a demonstration study in South Africa.

• DOI: 10.1038/s41598-023-43467-2
• 发表时间: 2023-09-27
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Denny, Lynette;Saidu, Rakiya;Boa, Rosalind;Mbatani, Nomonde;Castor, Delivette;Moodley, Jennifer;Kuhn, Louise
• 通讯作者: Kuhn, Louise

Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women.

• DOI: 10.1002/cam4.3329
• 发表时间: 2020-09
• 期刊: Cancer medicine
• 影响因子: 4
• 作者: Johnson LG;Saidu R;Mbulawa Z;Williamson AL;Boa R;Tergas A;Moodley J;Persing D;Campbell S;Tsai WY;Wright TC;Denny L;Kuhn L
• 通讯作者: Kuhn L

Performance of Xpert HPV on Self-collected Vaginal Samples for Cervical Cancer Screening Among Women in South Africa.

XPERT HPV在南非女性中进行宫颈癌筛查的自我收集的阴道样品的性能。

• DOI: 10.1097/lgt.0000000000000575
• 发表时间: 2021-01-01
• 期刊: Journal of lower genital tract disease
• 影响因子: 3.7
• 作者: Saidu R;Kuhn L;Tergas A;Boa R;Moodley J;Svanholm-Barrie C;Persing D;Campbell S;Tsai WY;Wright TC;Denny L
• 通讯作者: Denny L

Clinical evaluation of modifications to a human papillomavirus assay to optimise its utility for cervical cancer screening in low-resource settings: a diagnostic accuracy study.

• DOI: 10.1016/s2214-109x(19)30527-3
• 发表时间: 2020-03
• 期刊: The Lancet. Global health
• 作者: Kuhn L;Saidu R;Boa R;Tergas A;Moodley J;Persing D;Campbell S;Tsai WY;Wright TC;Denny L
• 通讯作者: Denny L

Assessing the diagnostic value of Xpert HPV - Authors' reply.

评估 Xpert HPV 的诊断价值 - 作者的回复。

• DOI: 10.1016/s2214-109x(20)30296-5
• 发表时间: 2020
• 期刊: The Lancet. Global health
• 作者: Kuhn,Louise;Saidu,Rakiya;Denny,Lynette
• 通讯作者: Denny,Lynette