title: Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  VU University Medical Center, Erasmus University Medical Center, Netherlands.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Kocken
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkhof
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Louwers
authors.forename: Mariëlle A E
authors.initials: MA
authors.lastname: Nobbenhuis
authors.forename: Aagje G
authors.initials: AG
authors.lastname: Bais
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Hogewoning
authors.forename: Afra
authors.initials: A
authors.lastname: Zaal
authors.forename: René H M
authors.initials: RH
authors.lastname: Verheijen
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D052685:Alphapapillomavirus / Q000302:isolation & purification; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011159:Population Surveillance / Q000379:methods*; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D014412:Tumor Virus Infections / Q000150:complications / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy / Q000821:virology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000628:therapy / Q000821:virology