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Triage of women with equivocal or low-grade cervical cytology results: a meta-analysis of the HPV test positivity rate
Authors:Marc Arbyn  Pierre Martin-Hirsch  Frank Buntinx  Marc Van Ranst  Evangelos Paraskevaidis  Joakim Dillner
Institution:Unit of Cancer Epidemiology, Scientific Institute of Public Health, Brussels, Belgium;ECCG (European Cooperation on development and implementation of Cancer screening and prevention Guidelines, IARC, Lyon, France;CCPRB (Cancer Control using Population-based cancer Registries and Biobanking) Network, Lund University, Malmö, Sweden;Central Lancashire Teaching Hospitals, Preston, UK;Belgian Centre of Evidence-Based Medicine, Belgian Branch of the Cochrane Collaboration, University of Leuven, Belgium;Department of General Practice, University of Leuven, Belgium &University of Maastricht, The Netherlands;Department of Clinical and Epidemiological Virology, University of Leuven, Belgium;Department of Obstetrics and Gynaecology, University Hospital of Ioannina, Greece;Department of Medical Microbiology, Lund University, MalmöUniversity Hospital, Malmö, Sweden
Abstract:Consistent evidence underlines the utility of human papillomavirus (HPV) DNA testing in the management of women with equivocal cervical cytological abnormalities, but not in case of low-grade lesions. We performed a meta-analysis including studies where the high-risk probe of the Hybrid Capture-II is used to triage these two cytological categories. The triage test-positivity rate reflects the colposcopy referral workload.Data were pooled on the HPV test positivity rate in women with atypical squamous cells of undetermined significance (ASCUS/ASC-US) or low-grade squamous intraepithelial lesions (LSIL), derived from different cytological classification systems. The meta-analysis was restricted to studies, published between 1991 and 2007. A random-effect model was applied for meta-analytical pooling and the influence of covariates on the HPV positivity rate was analyzed by meta-regression. The variation by age was assessed within individual studies since age strata were not defined uniformly. On an average, 43% (95% CI: 40–46%) of women with ASCUS/ASC-US were high-risk HPV positive (range 23–74%). In women with LSIL, the pooled positivity rate was 76% (95% CI: 71–81%; range 55–89%). In spite of considerable inter-study heterogeneity, the difference in HPV positivity between the two triage groups was large and highly significant: 32% (95% CI: 27–38%). HPV rates dropped tremendously as age and cutoffs of test positivity increased. Other factors (cytological classification system, country, continent, collection method and year of publication) had no statistically significant impact, except in LSIL triage where HPV positivity was significantly lower in European compared to American studies. Women with LSIL, especially younger women, have high HPV positivity rates suggesting limited utility of reflex HPV triaging these cases. Research is needed to identify more specific methods to triage women with low-grade squamous cervical lesions.
Keywords:cervical cancer  atypical squamous cells of undetermined significance  low-grade squamous intraepithelial lesions  triage  human papillomavirus  HPV  meta-analysis
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