Grant Number:	5UH3CA189908-05 Interpret this number
Primary Investigator:	Kuhn, Louise
Organization:	Columbia University Health Sciences
Project Title:	Improving Specificity of HPV Screen-and-Treat in South Africa
Fiscal Year:	2018

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.




Point-of-care testing with Xpert HPV for single-visit, screen-and-treat for cervical cancer prevention: a demonstration study in South Africa.
Authors: Denny L. , Saidu R. , Boa R. , Mbatani N. , Castor D. , Moodley J. , Kuhn L. .
Source: Scientific reports, 2023-09-27; 13(1), p. 16182.
EPub date: 2023-09-27.
PMID: 37758811
Related Citations

Clinical Utility of Reflex Testing with Cancer Biomarkers to Improve Diagnostic Accuracy of Primary Human Papillomavirus Screening.
Authors: Johnson L.G. , Saidu R. , Svanholm-Barrie C. , Boa R. , Moodley J. , Tergas A. , Persing D. , Campbell S.A. , Tsai W.Y. , Wright T.C. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2022-03-01; 31(3), p. 595-603.
PMID: 35027434
Related Citations

Performance of Xpert HPV on Self-collected Vaginal Samples for Cervical Cancer Screening Among Women in South Africa.
Authors: Saidu R. , Kuhn L. , Tergas A. , Boa R. , Moodley J. , Svanholm-Barrie C. , Persing D. , Campbell S. , Tsai W.Y. , Wright T.C. , et al. .
Source: Journal of lower genital tract disease, 2021-01-01; 25(1), p. 15-21.
PMID: 33105451
Related Citations

Selecting human papillomavirus genotypes to optimize the performance of screening tests among South African women.
Authors: Johnson L.G. , Saidu R. , Mbulawa Z. , Williamson A.L. , Boa R. , Tergas A. , Moodley J. , Persing D. , Campbell S. , Tsai W.Y. , et al. .
Source: Cancer medicine, 2020 Sep; 9(18), p. 6813-6824.
EPub date: 2020-07-24.
PMID: 32706163
Related Citations

Assessing the diagnostic value of Xpert HPV - Authors' reply.
Authors: Kuhn L. , Saidu R. , Denny L. .
Source: The Lancet. Global health, 2020 Aug; 8(8), p. e998.
PMID: 32710877
Related Citations

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.
Authors: Kuhn L. , Saidu R. , Boa R. , Tergas A. , Moodley J. , Persing D. , Campbell S. , Tsai W.Y. , Wright T.C. , Denny L. .
Source: The Lancet. Global health, 2020 Feb; 8(2), p. e296-e304.
PMID: 31981559
Related Citations

[Not Available].

Error Notice