Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study

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.