title: Risk of high-grade cervical intra-epithelial neoplasia based on cytology and high-risk HPV testing at baseline and at 6-months.
abstract: Adding a test for high-risk human papillomavirus (hrHPV) to cytological screening enhances the detection of high-grade cervical intraepithelial neoplasia (>or=CIN2), but data are required that enable long-term evaluation of screening. We investigated the >or=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 >or=CIN2 diagnosed within 36 months. hrHPV testing was more sensitive than cytology for >or=CIN2 (relative sensitivity 1.4, 95%CI: 1.3-1.5; absolute sensitivity 94.1 and 68.0%, respectively). The 18-month >or=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 >or=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 >or=CIN2 risk. Notably, women who had a double negative repeat test at 6 months had a >or=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 >or=CIN2 risk of 0% (95%CI: 0.0-0.8). Using hrHPV and/or cytology testing, risk of >or=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.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Bulk
authors.forename: Nicole W J
authors.initials: NW
authors.lastname: Bulkmans
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rozendaal
authors.forename: A Joan P
authors.initials: AJ
authors.lastname: Boeke
authors.forename: René H M
authors.initials: RH
authors.lastname: Verheijen
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D003127:Colposcopy / Q000379:methods* / Q000592:standards; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008403:Mass Screening / Q000379:methods / Q000592:standards; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears / Q000379:methods* / Q000592:standards; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000821:virology