The Lancet Oncology

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

Mariëlle Kocken MD a b, Prof Theo JM Helmerhorst MD a, Johannes Berkhof PhD d, Jacqueline A Louwers MD b c, Mariëlle AE Nobbenhuis MD a e, Aagje G Bais MD a, Cornelis JA Hogewoning MD f, Afra Zaal MD g, Prof René HM Verheijen MD g, Prof Peter JF Snijders PhD b, Prof Chris JLM Meijer MD b 

Summary

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.

Funding

VU University Medical Center, Erasmus University Medical Center, Netherlands.

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