title: Evaluation of 14 triage strategies for HPV DNA-positive women in population-based cervical screening.
abstract: High-risk human papillomavirus (hrHPV) testing has a higher sensitivity but lower specificity than cytology for detection of high-grade intraepithelial neoplasia (CIN). To avoid over-referral to colposcopy and overtreatment, hrHPV-positive women require triage testing and/or followup. A total of 25,658 women (30-60 years) enrolled in a population-based cohort study had an adequate baseline Pap smear and hrHPV test. The end-point was cumulative two-year risk of CIN grade 3 or worse (CIN3+). In a post-hoc analysis, fourteen triage/followup strategies for hrHPV-positive women (n = 1,303) were evaluated for colposcopy referral rate, positive (PPV) and negative predictive value (NPV). Five strategies involved triage testing without a repeat test and nine strategies involved triage testing followed by one repeat testing. The tests were cytology, hrHPV, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping. Results were adjusted for women in the cohort study who did not attend repeat testing. Of the strategies without repeat testing, combined cytology and HPV16/18/31/33/45 genotyping gave the highest NPV of 98.9% (95%CI 97.6-99.5%). The corresponding colposcopy referral rate was 58.1% (95%CI 55.4-60.8%). Eight of the nine strategies with retesting had an estimated NPV of at least 98%. Of those, cytology triage followed by cytology at 12 months had a markedly lower colposcopy referral rate of 33.4% (95%CI 30.2-36.7%) than the other strategies. The NPV of the latter strategy was 99.3% (95%CI 98.1-99.8%). Triage hrHPV-positive women with cytology, followed by repeat cytology testing yielded a high NPV and modest colposcopy referral rate and appear to be the most feasible management strategy.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dorien C
authors.initials: DC
authors.lastname: Rijkaart
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
authors.forename: Folkert J
authors.initials: FJ
authors.lastname: van Kemenade
authors.forename: Veerle M H
authors.initials: VM
authors.lastname: Coupe
authors.forename: Albertus T
authors.initials: AT
authors.lastname: Hesselink
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rozendaal
authors.forename: Danielle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Ren H
authors.initials: RH
authors.lastname: Verheijen
authors.forename: Saskia
authors.initials: S
authors.lastname: Bulk
authors.forename: Wim M
authors.initials: WM
authors.lastname: Verweij
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; D052685:Alphapapillomavirus / Q000235:genetics*; D004279:DNA, Viral / Q000737:chemistry; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000473:pathology / Q000821:virology; D012680:Sensitivity and Specificity; D014218:Triage / Q000379:methods*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral