Progression and regression of women with biopsy-confirmed normal cervical epithelium or cervical intraepithelial neoplasia grade 1: a 15-year population-based cohort study in China

Abstract Background The long-term risk of progression or regression in women with biopsy-confirmed normal cervical epithelium or cervical intraepithelial neoplasia grade 1 (CIN1) is unclear. The aim of the study was to assess the rates of progression and regression of women with histological CIN1 or normal cervical epithelium in rural China. Methods A screening cohort for cervical cancer was built in 1999 in Xiangyuan County, Shanxi Province, with a sample size of 1997 women aged 35–45 years, who were followed up in 2005 (6-year follow-up), 2010 (11-year follow-up), and 2014 (15-year follow-up) with human papillomavirus (HPV) DNA testing, liquid-based cytology, and visual inspection with acetic acid (except in 2014). Progression and regression rates of histological normal and CIN1 at different follow-up timepoints were calculated stratified by baseline HPV status. Findings The cumulative rate of progression to CIN2+ among women who were CIN1 baseline was 7% (8/107) at 6-year follow-up, 21% (22/103) at 11-year follow-up, and 24% (23/96) at 15-year follow-up. Women who were CIN1 and HPV-positive had significantly higher progression rates (13% [8/63] at 6 years, 33% [20/60] at 11 years, and 36% [21/59] at 15 years) than did those who were CIN1 but were negative for HPV (0% [0/44], 5% [2/43], and 5% [2/37], respectively; p=0·014 at 6 years, p=0·0005 at 11 years, and p=0·0007 at 15 years). Meanwhile, up to 95% of women who were CIN1 and HPV negative at baseline regressed to normal during the 15-year period. Furthermore, the rates of progression to CIN2+ among women who were histologically normal was 1% (11/1543) at 6-year follow-up, 3% (40/1358) at 11-year follow-up, and 5% (60/1162) at 15-year follow-up; more than 90% of women maintained at normal during the 15-year period. Interpretation HPV testing could be helpful to monitor women with CIN1 or normal cervical epithelium. The screening interval for those without HPV infection could be safely extended to 5–10 years, but those who are HPV-positive should be followed closely. Funding National Natural Science Foundation of China (grant number 81050018, 81322040, 81402748); Chinese Academy of Medical Science Initiative for Innovative Medicine (2016-I2M-1-019).