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

Abstract

Supplemental digital content is available in the text. 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 I2 and τ2 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, I2 = 92%), 25% (95% CI = 20–30, I2 = 94%), 11% (95% CI = 8–13, I2 = 89%), and 2% (95% CI = 1–3, I2 = 82%), respectively. The overall regression, persistence, and progression rates for CIN 2 were 55% (95% CI = 50–60, I2 = 85%), 23% (95% CI = 19–28, I2 = 83%), and 19% (95% CI = 15–23, I2 = 88%), respectively. Finally, for CIN 3, these were 28% (95% CI = 17–41, I2 = 68%), 67% (95% CI = 36–91, I2 = 84%), and 2% (95% CI = 0–25, I2 = 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, I2 = 76%; 94%, 95% CI = 84–99, I2 = 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.