Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months

Authors

  • Saskia Bulk,

    1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
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    • Saskia Bulk and Nicole W.J. Bulkmans have contributed equally to this manuscript. Bulk performed the analyses and prepared the manuscript. N.W.J. Bulkmans was responsible for the data collection. J. Berkhof was responsible for the conception of the study and statistical methods. P.J.F. Snijders was responsible for the virology determinations. C.J.L.M. Meijer was the principal investigator of the project, and had access to all data and final responsibility for the decision to submit for publication. All authors participated in the preparation of the design of the study, interpretation of data, writing of the manuscript and approved the final version of the manuscript.

  • Nicole W.J. Bulkmans,

    1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
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    • Saskia Bulk and Nicole W.J. Bulkmans have contributed equally to this manuscript. Bulk performed the analyses and prepared the manuscript. N.W.J. Bulkmans was responsible for the data collection. J. Berkhof was responsible for the conception of the study and statistical methods. P.J.F. Snijders was responsible for the virology determinations. C.J.L.M. Meijer was the principal investigator of the project, and had access to all data and final responsibility for the decision to submit for publication. All authors participated in the preparation of the design of the study, interpretation of data, writing of the manuscript and approved the final version of the manuscript.

  • Johannes Berkhof,

    1. Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, The Netherlands
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  • Lawrence Rozendaal,

    1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
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  • A. Joan P. Boeke,

    1. Department of General Practice, Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands
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  • René H.M. Verheijen,

    1. Department of Obstetrics and Gynaecology, Division of Gynecologic Oncology, VU University Medical Center, The Netherlands
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  • Peter J.F. Snijders,

    1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
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  • Chris J.L.M. Meijer

    Corresponding author
    1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
    • Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands
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    • Fax: +31-20-444-2964


  • POBASCAM study collaborators other than authors: Dr. K. V Groningen (Spaarne Ziekenhuis, Hoofddorp), Dr. W. Ruitinga (Kennemer Gasthuis, Haarlem), Dr. M.E. Boon (Leiden Cytology and Pathology Laboratory, Leiden), Dr. M. van Ballegooijen (Department of Public Health and Social Medicine, Erasmus University Rotterdam), Dr. F.J. Voorhorst and Dr. F.J. van Kemenade (Unit cytopathology, VU University Medical Center, Amsterdam).

Abstract

Adding a test for high-risk human papillomavirus (hrHPV) to cytological screening enhances the detection of high-grade cervical intraepithelial neoplasia (≥CIN2), but data are required that enable long-term evaluation of screening. We investigated the ≥CIN2 risk for women participating in population-based screening as a function of hrHPV and cytology testing results at baseline and at 6 months. We included 2,193 women aged 30–60 years participating in a population-based screening trial who received colposcopy or a repeat testing advice at baseline. The main endpoint was histologically confirmed ≥CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for ≥CIN2 (relative sensitivity 1.4, 95%CI: 1.3–1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18-month ≥CIN2 risks in women with a hrHPV-positive smear and in women with abnormal cytology were similar (relative risk 0.9, 95%CI: 0.8–1.1). Women with HPV16 and/or HPV18 had a higher ≥CIN2 risk than other hrHPV-positive women irrespective of the cytological grade. Repeat testing showed that both cytological regression and viral clearance were strongly associated with a decrease in ≥CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a ≥CIN2 risk of only 0.2% (95%CI: 0.0–1.1) and hrHPV-negative women with baseline borderline or mild dyskaryosis and normal cytology at 6 months had a ≥CIN2 risk of 0% (95%CI: 0.0–0.8). Using hrHPV and/or cytology testing, risk of ≥CIN2 can be assessed more accurately by repeat testing than single visit testing. Hence, when hrHPV testing is implemented, patient management with repeat testing is a promising strategy to control the number of referrals for colposcopy. © 2007 Wiley-Liss, Inc.

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