Kocken, M., Helmerhorst, T. J. M., Berkhof, J., Louwers, J. A., Nobbenhuis, M. A. E., Bais, A. G., Hogewoning, C. J. A., Zaal, A., Verheijen, R. H. M., Snijders, P. J. F., Meijer, Cjlm (2011) Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. LANCET ONCOLOGY, 12 (5). pp. 441-450. ISSN 1470-2045

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Abstract

Background 15% of women treated for high-grade cervical intraepithelial neoplasia (CIN grade 2 or 3) develop residual or recurrent CIN grade 2 or 3 or cervical cancer, most of which are diagnosed within 2 years of treatment. To gain more insight into the long-term predictive value of different post-treatment strategies, we assessed the long-term cumulative risk of post-treatment CIN grade 2 or 3 or cancer and different follow-up algorithms to identify women at risk of residual or recurrent disease. Methods Women who were included in three studies in the Netherlands and who were treated for CIN grade 2 or 3 between July, 1988, and November, 2004, were followed up by cytology and testing for high-risk human papillomavirus (hrHPV) at 6,12, and 24 months after treatment, and subsequently received cytological screening every 5 years. The primary endpoint was the cumulative risk of post-treatment CIN grade 2 or higher by December, 2009. We also assessed the cumulative risk of CIN grade 2 or higher in women with three consecutive negative cytological smears and women with negative co-testing with cytology and hrHPV at months 6 and 24. This study is registered in the Dutch trial register, NTR1468. Findings 435 women were included, 76 (17%) of whom developed post-treatment CIN grade 2 or higher, of which 39 were CIN grade 3 or higher. The 5-year risk of developing post-treatment CIN grade 2 or higher was 16.5% (95% CI 13.0-20.7) and the 10-year risk was 18.3% (13.8-24.0). The 5-year risk of developing post-treatment CIN grade 3 or higher was 8.6% (95% CI 6.0-12.1) and the 10-year risk was 9.2% (5.8-14.2). Women with three consecutive negative cytological smears had a CIN grade 2 or higher risk of 2.9% (95% CI 1.2-7.1) in the next 5 years and of 5.2% (2.1-12.4) in the next 10 years. The 5-year risk of CIN grade 3 or higher was 0.7% (95% CI 0.0-3.9) and the 10-year risk was 0.7% (0.0-6.3). Women with negative results for co-testing had a 5-year risk of CIN grade 2 or higher of 1.0% (95% CI 0.2-4.6) and a 10-year risk of 3.6% (1-1-10.7). The 5-year risk of CIN grade 3 or higher was 0.0% (95% CI 0.0-3.0) and the 10-year risk was 0.0% (0.0-5.3). Interpretation The 5-year risk of post-treatment CIN grade 2 or higher in women with three consecutive negative cytological smears or negative co-testing for cytology and hrHPV at 6 and 24 months was similar to that of women with normal cytology in population-based screening and therefore justifies their return to regular screening.

Item Type:	Article
All Authors:	Kocken, M., Helmerhorst, T. J. M., Berkhof, J., Louwers, J. A., Nobbenhuis, M. A. E., Bais, A. G., Hogewoning, C. J. A., Zaal, A., Verheijen, R. H. M., Snijders, P. J. F., Meijer, Cjlm
Additional Information:	ISI Document Delivery No.: 771FQ Times Cited: 0 Cited Reference Count: 36 Kocken, Marielle Helmerhorst, Theo J. M. Berkhof, Johannes Louwers, Jacqueline A. Nobbenhuis, Marielle A. E. Bais, Aagje G. Hogewoning, Cornelis J. A. Zaal, Afra Verheijen, Rene H. M. Snijders, Peter J. F. Meijer, Chris J. L. M. VU University Medical Center ; Erasmus University Medical Center, Netherlands ; VU University Medical Center Amsterdam ; Erasmus MC University Medical Center Rotterdam, Netherlands ; Roche ; Gen Probe ; Qiagen Funding VU University Medical Center, Erasmus University Medical Center, Netherlands. This study was funded by the VU University Medical Center Amsterdam and Erasmus MC University Medical Center Rotterdam, Netherlands. We thank research staff and technicians from the unit of molecular pathology for HPV DNA testing and logistics, the cyto-technicians for cytological testing and logistics, and the information technology team from the Department of Pathology, VU University Medical Center for their supportive work. We also thank the team of the outpatient clinic of the Department of Obstetrics and Gynaecology, VU University Medical Center, and cyto-technicians and the team from the outpatient clinic at the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center. In addition, we thank all women who participated in our study. In the past 3 years PJFS has received consultancy fees from Roche and Gen Probe and speakers fees from Roche. In the past 3 years, CJLMM has received speakers fees from Qiagen and Roche and his institution has received board membership and consultancy fees from Qiagen. PJFS and CJLMM are listed on a patent for HPV detection by GP5+/6+ PCR through Qiagen for which their institution receives honoraria and CJLMM has received honoraria and is listed on a patent on promotor methylation of TSLC1 as a specific marked for CIN grade 2 or 3 or cervical cancer through Oncomethylome Science, now MDxHealth, for which his institution receives honoraria. All other authors declared no conflicts of interest. Elsevier science inc New york
Uncontrolled Keywords:	randomized clinical-trial hpv-dna detection of-the-literature human-papillomavirus follow-up residual/recurrent disease women cancer cin metaanalysis
Research teams:	Clinical Units > Other Royal Marsden Services/Clinical Units
Depositing User:	Users 11 not found.
Date Deposited:	21 Jun 2011 10:56
Last Modified:	10 Aug 2011 14:00
URI:	http://publications.icr.ac.uk/id/eprint/10788

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