The Natural History of Cervical Intraepithelial Neoplasia Grades 1, 2, and 3: A Systematic Review and Meta-analysis

Diede L. Loopik*, Heidi A. Bentley, Maria N. Eijgenraam, Joanna IntHout, Ruud L. M. Bekkers, James R. Bentley

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

8 Citations (Web of Science)

Abstract

Objective The aim of the study was to obtain an updated overview of regression, persistence, and progression rates of conservatively managed cervical intraepithelial neoplasia grade 1 (CIN 1)/CIN 2/CIN 3. Methods Data sources were MEDLINE, Embase, and Cochrane (January 1, 1973-April 14, 2020). Two reviewers extracted data and assessed risk of bias. To estimate outcome rates, we pooled proportions of the individual study results using random-effects meta-analysis, resulting in point estimates and corresponding 95% CIs. Heterogeneity was quantified by the I-2 and tau(2) measures. Results Eighty-nine studies were included, 63 studies on CIN 1 (n = 6,080-8,767), 42 on CIN 2 (n = 2,909-3,830), and 7 on CIN 3 (n = 245-351). The overall regression, persistence, and progression to CIN 2 or worse and CIN 3 or worse rates for women with conservatively managed CIN 1 were 60% (95% CI = 55-65, I-2 = 92%), 25% (95% CI = 20-30, I-2 = 94%), 11% (95% CI = 8-13, I-2 = 89%), and 2% (95% CI = 1-3, I-2 = 82%), respectively. The overall regression, persistence, and progression rates for CIN 2 were 55% (95% CI = 50-60, I-2 = 85%), 23% (95% CI = 19-28, I-2 = 83%), and 19% (95% CI = 15-23, I-2 = 88%), respectively. Finally, for CIN 3, these were 28% (95% CI = 17-41, I-2 = 68%), 67% (95% CI = 36-91, I-2 = 84%), and 2% (95% CI = 0-25, I-2 = 95%), respectively. Cervical intraepithelial neoplasia grade 2 regression was significantly higher in women 30 years or younger and high-risk human papillomavirus-negative women (66%, 95% CI = 62-70, I-2 = 76%; 94%, 95% CI = 84-99, I-2 = 60%). Only 2/7,180 (0.03%) and 10/3,037 (0.3%) of the CIN 1 and CIN 2 cases progressed to cervical cancer. Conclusions Most CIN 1/CIN 2 will regress spontaneously in less than 24 months, with the highest rates in high-risk human papillomavirus-negative and young women, whereas progression to cancer is less than 0.5%. Conservative management should be considered, especially in fertile women and with expected high compliance. Given the heterogeneity in regression rates of high-grade histology, this should be classified as CIN 2 or CIN 3 to guide management.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalJournal of Lower Genital Tract Disease
Volume25
Issue number3
DOIs
Publication statusPublished - Jul 2021

Keywords

  • cervical intraepithelial neoplasia
  • conservative treatment
  • disease progression
  • meta-analysis
  • neoplasm grading
  • review
  • systematic review
  • uterine cervical dysplasia
  • uterine cervical neoplasms
  • CANCER SCREENING-TESTS
  • HUMAN-PAPILLOMAVIRUS
  • FOLLOW-UP
  • PREDICTIVE-VALUE
  • DOUBLE-BLIND
  • CONSERVATIVE MANAGEMENT
  • EXPECTANT MANAGEMENT
  • PROGNOSTIC-FACTORS
  • SPONTANEOUS REGRESSION
  • P16(INK4A) EXPRESSION

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