Abstract

BackgroundIt is well acknowledged that HPV testing should not be performed at young age and at short intervals. Cytological screening practices have shown that over-screening, i.e., from a younger age and at shorter intervals than recommended, is hard to avoid. We quantified the consequences of a switch to primary HPV screening for over-screened women, taking into account its higher sensitivity but lower specificity than cytology.MethodsThe health effects of using the HPV test instead of cytology as the primary screening method were determined with the MISCAN-Cervix model. We varied the age women start screening and the interval between screens. In the sensitivity analyses, we varied the background risk of cervical cancer, the HPV prevalence, the discount rate, the triage strategy after cytology, and the test characteristics of both cytology and the HPV test.ResultsFor women screened 5 yearly from age 30, 32 extra deaths per 100,000 simulated women were prevented when switching from primary cytology to primary HPV testing. For annual screening from age 20, such a switch resulted in 6 extra deaths prevented. It was associated with 9,044 more positive primary screens in the former scenario versus 76,480 in the latter. Under all conditions, for women screened annually, switching to HPV screening resulted in a net loss of quality-adjusted life years.ConclusionFor over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary HPV testing. The extent of over-screening should be considered when deciding on inclusion of primary HPV screening in cervical cancer screening guidelines.Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-016-0732-7) contains supplementary material, which is available to authorized users.

Highlights

  • In several Western countries, cytological screening has considerably reduced the cervical cancer incidence and mortality over the past four decades [1]

  • For over-screened women, the harms associated with a lower test specificity outweigh the life years gained when switching from primary cytology to primary human papillomavirus (HPV) testing

  • HPV human papillomavirus, CIN cervical intraepithelial neoplasia, ASCUS atypical squamous cells of undetermined significance, high-grade squamous intraepithelial lesion (HSIL) highgrade squamous intraepithelial lesion a Depends on age, age dependency was not varied b The number of false-positive referrals to colposcopy and CIN grade I lesions was doubled c Value was determined in model calibration d Probability to detect an HPV infection, regardless of whether a CIN lesion or cancer is present e A possible lack of specificity was modeled by including fast-clearing HPV infections f As a lower specificity of the HPV test corresponds with a higher prevalence of harmless HPV infections in the model, this parameter was not varied

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Summary

Introduction

In several Western countries, cytological screening has considerably reduced the cervical cancer incidence and mortality over the past four decades [1]. A summary of meta-analyses estimated that the HPV test has a 23 % (95 % CI 13–33 %) higher sensitivity, but a 6 % (95 % CI 4–8 %) lower specificity than cytology for detecting high-grade lesions and cervical cancer [8]. HPV human papillomavirus, CIN cervical intraepithelial neoplasia, ASCUS atypical squamous cells of undetermined significance, HSIL highgrade squamous intraepithelial lesion a Depends on age, age dependency was not varied b The number of false-positive referrals to colposcopy and CIN grade I lesions was doubled c Value was determined in model calibration d Probability to detect an HPV infection, regardless of whether a CIN lesion or cancer is present e A possible lack of specificity was modeled by including fast-clearing HPV infections f As a lower specificity of the HPV test corresponds with a higher prevalence of harmless HPV infections in the model, this parameter was not varied. No risk of cervical in CIN grade I or cytology ; cytology ; HPV test : HPV test ; xtriaged as in discounting cancer mortality : lessa : Dutch program 5% discounting

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