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Posttreatment Assessment of Women at Risk of Developing High-Grade Cervical Disease: Proposal for New Guidelines Based on Data From The Netherlands

H. Uijterwaal, Margot MD1; Kocken, Mariëlle MD, PhD1; Berkhof, Johannes PhD2; Bekkers, Ruud L.M. MD, PhD3; H.M. Verheijen, Réne MD, PhD4; Helmerhorst, Theo J.M. MD, PhD5; Meijer, Chris J.L.M. MD, PhD,1

Journal of Lower Genital Tract Disease: October 2014 - Volume 18 - Issue 4 - p 338–343
doi: 10.1097/LGT.0000000000000012
Review Article

Objective: Women treated for high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or grade 3 [CIN2/3]) face a significant risk of developing post-treatment disease. Therefore, in most European countries, they are monitored by cytologic testing at 6, 12, and 24 months after treatment. Although testing for high-risk types of the human papillomavirus (hrHPV) in the follow-up seems to be a valuable supplementary method, its use is not yet fully explored.

Methods: Besides reviewing the literature, we completed a long-term follow-up study describing the cumulative risk for CIN2/3 or cancer (CIN2+) of different hrHPV and cytology test results after treatment.

Conclusions: High-risk HPV testing improves the sensitivity to detect posttreatment CIN2/3 (relative sensitivity = 1.15, 95% confidence interval [CI] = 1.06–1.25), but the highest sensitivity (95%, 95% CI = 91%–98%) is reached by performing cotesting (both cytology and hrHPV). The CIN2+ risk after a single negative cotesting result taken 6 months after treatments was similar to the risk after 3 consecutive negative cytologic test results (5-y CIN2+ risk being 3.0% [95% CI = 1.5%–6.1%] and 2.9% [95% CI = 1.2%–7.1%], respectively). Women who test negative for cotesting at both 6 and 24 months after treatment have a minimal risk of developing CIN3+ in the next 5 years (0.0%, 95% CI = 0.0%–3.0%).

Recommendations: We propose a new posttreatment surveillance protocol, consisting of combined testing with both cytology and hrHPV at 6 and 24 months after treatment. After 2 negative cotesting results, women should be retested after 5 years.

We recommend a new posttreatment surveillance protocol, consisting of combined testing with both cytology and high-risk types of the human papillomavirus at 6 and 24 months after treatment.

Departments of 1Pathology and 2Epidemiology and Biostatistics, VU University Medical Center, Amsterdam; 3Department of Obstetrics and Gynecology, University Nijmegen Medical Center, Nijmegen; 4Department of Women and Baby, University Medical Center Utrecht, Utrecht; and 5Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, The Netherlands

Reprint requests to: Mariëlle Kocken, MD, PhD, Department of Pathology, VU University Medical Center, PO BOX 7057, 1000 MB Amsterdam, The Netherlands. E-mail: m.kocken@vumc.nl

C.M. has been a member of the scientific advisory board of Qiagen and has received occasionally speaker’s fees from GlaxoSmithKline, Merck, and Roche; and his institution has received board membership and consultancy fees from Qiagen. C.M. holds a patent for HPV detection by GP5+/6+ PCR through Qiagen for which their institution receives honoraria. C.M. holds stock of Self-screen, a spinoff company of VU Medical Center.

R.B. has been on the advisory board of GSK and has received speakers’ fees from Roche and research grants from GSK, Sanofi Pasteur, and Roche. The other authors (M.K., M.U., T.H., J.B., and R.V.) declare that they have no conflicts of interest. M. Uijterwaal and M. Kocken contributed equally to this article.

The authors thank The Dutch Cancer Society for granting support for this work (KWF VU 2009-4413).

All authors have made substantial contributions to the concept, design, and writing of the article. All authors qualified for authorship have been included and confirm that this article has been read and approved by all of them.

Copyright © 2014 by the American Society for Colposcopy and Cervical Pathology