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Grand Rounds

What Are the Risk Factors for Recurrence after Large Loop Excision for CIN 2/3?

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BACKGROUND AND PURPOSE:

  • Long-term risk for CIN recurrence following large loop excision of the transformation zone (LLETZ) remains unclear
  • Fernández-Montolí et al. (BJOG, 2019) examined the long-term risk factors associated with
    • Recurrent cervical intraepithelial neoplasia (CIN 2/3)
    • Time to recurrence after LLETZ

METHODS:

  • Retrospective study
    • 1996 and 2006 with follow-up until 2016
  • Participants
    • Women with CIN 2/3
    • Consecutively treated with LLETZ
  • Study design
    • Loop size based on the tissue to be excised
      • Second selective EC sweep with a smaller loop if the transformation zone was type 3 or if the patient >35 years
    • Residual/recurrent disease was defined as CIN 2/3 diagnosed by cervical biopsy or endocervical curettage | CIN2 and CIN3 combined due to anticipated small ‘n’
    • Logistic regression models used to estimate
      • Age | Margins | Association with high-risk human papillomavirus (HR-HPV)
  • Primary outcome
    • Histologically confirmed CIN 2/3

RESULTS:

  • 242 women included
  • CIN 2/3 following LLETZ was associated with
    • HR-HPV after LLETZ: HR 30.5 (95% CI, 3.80 to 246.20; P < 0.001)
      • Sensitivity of 88.8%; specificity of 80%
    • Age >35 years: HR 5.53 (95% CI, 1.22 to 25.13; P = 0.009)
    • Involved margins: HR 7.31, 95% CI = 1.60 to 33.44; P = 0.003)
  • The following margins had a higher risk of recurrence
    • Ecto+/endocervical+: 16.7%
      • Odds ratio (OR) 13.20 (95% CI, 1.02 to 170.96)
    • Uncertain: 19.4%
      • OR 15.84 (95% CI, 3.02 to 83.01)
    • Ecto−/endocervical+: 9.1%
      • OR 6.60 (95% CI, 0.88 to 49.53)
  • 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)

CONCLUSION:

  • >35 years, HR-HPV positive and involved margins are at a higher risk of CIN 2/3 recurrence post-LLETZ
  • Post-treatment HR-HPV has a demonstrated a higher sensitivity and NPV than cytology or margins for detecting the residual or recurrent CIN
  • Authors suggest risk factors such as age should be taken into account, including larger excision in older women to obtain clear margins |  “HR-HPV and margin statuses can be used to stratify the post-LLETZ risk of recurrence and enable personalised management”

Learn More – Primary Sources:

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

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Related ObG Topics:

HPV Vaccines: Cochrane Reviews Looks at the Evidence with Multi-Year Follow-Up
HPV Genotyping and Cytology for hrHPV: What Screening Combination is Best for CIN Detection?
Treatment for Women with HIV and High-Grade Cervical Lesions: Cryotherapy or LEEP?

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