SOX1 methylation predicts postoperative pathological downgrading in CIN3 lesions before biopsy

A proportion of CIN3 lesions diagnosed by colposcopic biopsy showed downgrading on pathology following cone biopsy. The accurate identification of CIN3 lesions with downgrading potential before surgery is clinically valuable, as it enables the avoidance of overtreatment and the preservation of fertility in women of childbearing age. However, no well-established, reliable molecular marker predicts postoperative pathological downgrading in CIN3 lesions before biopsy.

Four candidate methylation genes (SOX1, ZIC1, ZNF582, and miR129-2) that may be linked to the downgrading of CIN3 were identified in prior screening studies. In this observational study, we examined high-risk human papillomavirus (hrHPV) status, cytology findings, methylation analysis, and age collected during cervical screening. These variables were compared with postoperative pathological results to evaluate their ability to predict the postoperative pathological downgrading of CIN3.

Of the 161 patients diagnosed with CIN3 by colposcopy, the four genes could significantly distinguish postoperative CIN grade 1 (CIN1) or less (CIN1-) from CIN2 or worse (CIN2+) lesions. SOX1 methylation (SOX1^m) exhibited the greatest predictive ability for postoperative pathological downgrading among the four genes. The combination of negative SOX1^m status and age 35 or younger (≤35) more precisely predicted postoperative pathological downgrading, with an odds ratio of 42.709 (p = 0.013) and a negative predictive value of 100% (95% confidence interval [CI]: 39.58%-100%).

The current findings suggest the hypothesis that SOX1^m analyses may predict the postoperative pathological downgrading of CIN3 before biopsy. Further research is needed to determine whether conservative treatment, combined with careful monitoring and active follow-up, is appropriate for women aged ≤35 who test negative for SOX1^m.