Lan Xu1, Ina Benoy2, Kate Cuschieri3, Mario Poljak4, Jesper Bonde5, Marc Arbyn1. 1. a Unit of Cancer Epidemiology & Belgian Cancer Centre , Scientific Institute of Public Health , Brussels , Belgium. 2. b Department of Molecular Pathology , AML Laboratory, Sonic Healthcare , Antwerp , Belgium. 3. c Scottish HPV Reference Laboratory , Royal Infirmary of Edinburgh, Edinburgh , Scotland , UK. 4. d Institute of Microbiology and Immunology, Faculty of Medicine , University of Ljubljana , Ljubljana , Slovenia. 5. e Molecular Pathology Laboratory, Department of Pathology , Copenhagen University Hospital , Hvidovre , Denmark.
Abstract
Background: Genotyping for the most carcinogenic human papillomavirus (HPV) types (HPV16/HPV18) can identify high risk of underlying cervical precancer and guide further management. Research design and methods: A pooled analysis was performed of the clinical accuracy of high-risk HPV (hrHPV) testing and HPV16/18 genotyping in triage of women with low-grade squamous intraepithelial lesions (LSIL). Data regarding 24 assays evaluated in four VALGENT validation panels were used. Results: In women with LSIL, hrHPV had a pooled sensitivity for CIN2+ of 95.5% (95% CI: 91.0-97.8%) and a specificity of 25.3% (95% CI: 22.2-28.6%). HPV16/18 genotyping had a sensitivity and specificity for CIN2+ of 52.9% (95% CI: 48.4-57.4%) and 83.5% (95% CI: 79.9-86.5%), respectively. The average risk of CIN2+ was 46.1% when HPV16/18-positive, 15.5% in women who were HPV16/18-negative but positive for other hrHPV types and 4.3% for hrHPV-negative women. Conclusions: Triage of women with LSIL with HPV16/18 genotyping increases the positive predictive value compared to hrHPV testing but at the expense of lower sensitivity. Arguably, women testing positive for HPV16/18 need further clinical work-up. Whether colposcopy referral or further surveillance is recommended for women with other hrHPV types may depend on the post-test risk of precancer and the local risk-based decision thresholds.
Background: Genotyping for the most carcinogenic human papillomavirus (HPV) types (HPV16/HPV18) can identify high risk of underlying cervical precancer and guide further management. Research design and methods: A pooled analysis was performed of the clinical accuracy of high-risk HPV (hrHPV) testing and HPV16/18 genotyping in triage of women with low-grade squamous intraepithelial lesions (LSIL). Data regarding 24 assays evaluated in four VALGENT validation panels were used. Results: In women with LSIL, hrHPV had a pooled sensitivity for CIN2+ of 95.5% (95% CI: 91.0-97.8%) and a specificity of 25.3% (95% CI: 22.2-28.6%). HPV16/18 genotyping had a sensitivity and specificity for CIN2+ of 52.9% (95% CI: 48.4-57.4%) and 83.5% (95% CI: 79.9-86.5%), respectively. The average risk of CIN2+ was 46.1% when HPV16/18-positive, 15.5% in women who were HPV16/18-negative but positive for other hrHPV types and 4.3% for hrHPV-negative women. Conclusions: Triage of women with LSIL with HPV16/18 genotyping increases the positive predictive value compared to hrHPV testing but at the expense of lower sensitivity. Arguably, women testing positive for HPV16/18 need further clinical work-up. Whether colposcopy referral or further surveillance is recommended for women with other hrHPV types may depend on the post-test risk of precancer and the local risk-based decision thresholds.
Entities:
Keywords:
Cervical cancer screening; HPV genotyping; diagnostic test accuracy; low-grade squamous intraepithelial lesions; triage
Authors: Eliane Rohner; Claire Edelman; Busola Sanusi; John W Schmitt; Anna Baker; Kirsty Chesko; Brian Faherty; Sean M Gregory; LaHoma S Romocki; Vijay Sivaraman; Julie A E Nelson; Siobhan O'Connor; Michael G Hudgens; Andrea K Knittel; Lisa Rahangdale; Jennifer S Smith Journal: Cancer Epidemiol Biomarkers Prev Date: 2020-09-17 Impact factor: 4.254