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Early Detection and Diagnosis
Version of Record online: 5 MAY 2011
Copyright © 2011 UICC
International Journal of Cancer
Volume 130, Issue 3, pages 602–610, 1 February 2012
How to Cite
Rijkaart, D. C., Berkhof, J., van Kemenade, F. J., Coupe, V. M.H., Hesselink, A. T., Rozendaal, L., Heideman, D. A.M., Verheijen, R. H., Bulk, S., Verweij, W. M., Snijders, P. J.F. and Meijer, C. J.L.M. (2012), Evaluation of 14 triage strategies for HPV DNA-positive women in population-based cervical screening. Int. J. Cancer, 130: 602–610. doi: 10.1002/ijc.26056
CJLM was the project leader, designed the study with SB, LR and PJFS and had access to all data. DCR, together with JB, CJLM, FJvK, VC and PJFS, drafted the manuscript. DCR, JB and VC were responsible for data analysis. ATH, DAMH CJLM and PJFS were responsible for HPV testing and HPV genotyping. LR was responsible for database management. DCR and WMV were responsible for the logistics. RHMV was responsible for communication with gynaecologists. FJvK and LR were responsible for cytology testing. All authors critically reviewed the manuscript and approved the final version.
Conflict of interest: CJLM is a member of the Scientific advisory board of Qiagen (formerly Digene) and received lecture fees from GSK. PJFS provided occasional consultation to Roche and Gen-Probe. DAMH provided occasional consultation to Roche. Qiagen, Gen-Probe and Roche are companies involved with HPV diagnostics. RHMV received lecture fees from GSK and is a member of the advisory board of Delpi Biosciences. JB and VC received fees from GSK.
- Issue online: 24 NOV 2011
- Version of Record online: 5 MAY 2011
- Accepted manuscript online: 11 MAR 2011 11:04AM EST
- Manuscript Accepted: 26 JAN 2011
- Manuscript Received: 8 NOV 2010
- Stichting researchfonds Pathology; and Salto Laboratory Utrecht
- human papillomavirus;
- uterine cervical neoplasms;
- cervical intraepithelial neoplasia;
- early detection of cancer
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.