Long-Term Outcomes After Cervical Cold Knife Conization or Loop Electrosurgical Excision Procedure

Cold knife conization (CKC) and the loop electrosurgical excision procedure (LEEP) are standard treatments for cervical intraepithelial neoplasia and carcinoma in situ. However, the comparative long-term effectiveness of these procedures in promoting human papillomavirus (HPV) clearance and preventing recurrent cervical lesions remains uncertain.

To compare the long-term incidence of HPV clearance and recurrence of cervical lesions after CKC or LEEP.

This cohort study comprised 2 cohorts: a nationwide cohort from Sweden (cohort 1) and a multicenter hospital-based cohort from Fujian Province, China (cohort 2). The study dates were January 1, 1997, to December 31, 2013, for cohort 1 and from October 1, 2013, to October 1, 2022, for cohort 2. A target trial emulation framework was applied to evaluate the effectiveness of CKC vs LEEP, using inverse probability of censoring weighting to balance baseline covariates and address censoring. Women with cervical intraepithelial neoplasia or carcinoma in situ were included. Data were analyzed from October 1, 2024, to August 31, 2025.

Cold knife conization or the loop electrosurgical excision procedure.

The primary outcome was recurrence of cervical lesions. Secondary outcomes included HPV clearance at 3, 6, and 12 months (cohort 2). Weighted Cox models with hazard ratios (HRs) and 95% CIs were used to compare the recurrence of cervical lesions between CKC and LEEP, adjusting for clinical and demographic factors.

The total sample size was 77 001 women who underwent cervical conization in Sweden between 1997 and 2013. In cohort 1, after 22 years of follow-up, 16 017 of 75 497 (21.2%) women who underwent LEEP had recurrence, and 319 of 1504 (21.2%) women who underwent CKC had recurrence. In cohort 2, 65 of 3710 (1.8%) women who were treated with LEEP had recurrent cervical lesions compared with 11 (0.8%) recurrent cervical lesions among the 1340 women who were treated with CKC after 9 years of follow-up. In the hypothetical target trial, women who underwent CKC had a significantly lower risk of recurrence compared with those who underwent LEEP, with HR of 0.67 (95% CI, 0.65-0.68) in cohort 1 and 0.41 (95% CI, 0.21-0.79) in cohort 2. In addition, the HPV clearance rate after CKC was higher than that of LEEP at 3, 6, and 12 months in cohort 2.

These findings suggest that among women with cervical intraepithelial neoplasia or carcinoma in situ, CKC was associated with a lower risk of recurrent cervical lesions and higher HPV clearance rates compared with LEEP.