Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2-3 after treatment with a large loop excision of the transformation zone: a retrospective study

BJOG. 2020 Feb;127(3):377-387. doi: 10.1111/1471-0528.15996. Epub 2019 Dec 14.

Abstract

Objective: To assess the long-term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2-3) and time to recurrence after large loop excision of the transformation zone (LLETZ).

Design: Retrospective study.

Setting: Colposcopy clinic.

Population: 242 women with CIN 2-3 treated between 1996 and 2006 and followed up until June 2016.

Methods: Age, margins, and high-risk human papillomavirus (HR-HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan-Meier analysis.

Main outcome measure: Histologically confirmed CIN 2-3, HR-HPV, margins, age.

Results: CIN 2-3 was associated with HR-HPV (HR = 30.5, 95% confidence interval [CI] = 3.80-246.20), age >35 years (HR = 5.53, 95% CI = 1.22-25.13), and margins (HR = 7.31, 95% CI = 1.60-33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+ /endocervical+ (16.7%), uncertain (19.4%) and ecto- /endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02-170.96; OR = 15.84, 95% CI = 3.02-83.01; and OR = 6.60, 95% CI = 0.88-49.53, respectively). Women with involved margins and/or who were HR-HPV positive had more treatment failure than those who were HR-HPV negative or had clear margins (P-log-rank <0.001).

Conclusions: HR-HPV and margins seem essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk.

Tweetable abstract: After LLETZ for CIN 2-3, recurrences appear more often in women with positive HR-HPV and involved margins and aged over 35.

Keywords: Cervical intraepithelial neoplasia; HPV; margin status; recurrence.

MeSH terms

  • Cell Transformation, Neoplastic
  • Cervical Intraepithelial Neoplasia* / epidemiology
  • Cervical Intraepithelial Neoplasia* / pathology
  • Cervical Intraepithelial Neoplasia* / surgery
  • Cervix Uteri / pathology
  • Cervix Uteri / surgery
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Long Term Adverse Effects* / diagnosis
  • Long Term Adverse Effects* / epidemiology
  • Margins of Excision*
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm, Residual / diagnosis*
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / epidemiology
  • Retrospective Studies
  • Risk Assessment / methods
  • Spain / epidemiology
  • Trachelectomy* / adverse effects
  • Trachelectomy* / methods
  • Uterine Cervical Neoplasms* / epidemiology
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / surgery