One Surgical Technique for Cervical Lesions May Reduce Recurrences

Cold knife conization (CKC) was tied to a lower risk of recurrence of cervical lesions and higher human papillomavirus (HPV) clearance compared with the loop electrosurgical excision procedure (LEEP) among women with cervical intraepithelial neoplasia or carcinoma in situ, a cohort study suggested.

Across two cohorts from Sweden and China, target trial emulation showed that women who underwent CKC had a significantly lower risk of cervical lesion recurrence versus those who underwent LEEP, with hazard ratios of 0.67 (95% CI 0.65-0.68) in the Swedish cohort and 0.41 (95% CI 0.21-0.79) in the Chinese cohort, reported Huan Yi, MD, PhD, of Fujian Medical University in Fuzhou City, China, and colleagues.

After propensity score matching, the results consistently showed that the recurrence rate of cervical lesions after CKC surgery was lower than that after LEEP surgery, with hazard ratios of 0.65 (95% CI 0.52-0.82) in the Swedish cohort and 0.45 (95% CI 0.23-0.89) in the Chinese cohort, they wrote in JAMA Surgery.

Yi and colleagues found that 32.6% of recurrent cervical lesions in the Swedish cohort and 51.4% in the Chinese cohort could have potentially been prevented if all patients underwent CKC instead of LEEP.

Moreover, in the Chinese cohort, the HPV clearance rates at 3, 6, and 12 months were significantly higher following CKC versus LEEP. Previous studies comparing the two surgical modalities didn’t consider HPV infection after cervical conization.

Both LEEP and CKC are standard treatments for cervical intraepithelial neoplasia and carcinoma in situ, both of which are strongly associated with cervical cancer. For women with cervical intraepithelial neoplasia, treatment is crucial to prevent cervical cancer, the authors noted.

“Importantly, both LEEP and CKC are routinely available as standard-of-care modalities in the Chinese and Swedish healthcare systems, enabling genuine clinical choice rather than resource-driven selection,” Yi and team wrote.

CKC is an ambulatory operative procedure popularly used in Germany and China, while LEEP is an office-based electrocautery procedure more common throughout Europe, in part because of its lower cost, shorter operation time, and less bleeding. However, the long-term effectiveness of the procedures in terms of HPV clearance and preventing recurrence of cervical lesions has been uncertain.

Ultimately, the authors encouraged clinicians to make decisions on their surgical approach “based on a comprehensive evaluation of the patient’s pathologic status, individual clinical needs, and institutional facility capabilities.”

In an accompanying editorial, Jessica DiSilvestro, MD, and Jason Wright, MD, both of Tufts Medical Center in Boston, pointed out that while the findings were significant, the difference in incidence rates of recurrence was modest and the crude rates of recurrence between cohorts varied greatly.

“Both procedures provide unique benefits, and although potentially less effective in the long-term than a CKC, the in-office LEEP provides accessibility, which is crucial for patients who already face barriers to engaging in cervical cancer screening and prevention,” they wrote.

More research is needed on the factors that influence recurrence risk, DiSilvestro and Wright noted.

For this study, Yi and colleagues used a target trial framework to emulate a multicenter, open-label, 2-parallel arm randomized trial in which women with cervical intraepithelial neoplasia or cervical carcinoma in situ (identified with ICD-10 codes) would initiate CKC or LEEP in an unblinded fashion. There were two cohorts: a nationwide cohort from Sweden from January 1997 through December 2013 and a multicenter hospital-based cohort from Fujian Province in China from October 2013 to October 2022.

The Swedish cohort included 77,001 women who underwent cervical conization, including 12.97% with cervical intraepithelial neoplasia 1, 48.27% with cervical intraepithelial neoplasia 2/3, and 38.76% with carcinoma in situ. Most patients (98.1%) underwent LEEP (mean age at surgery 35.5), while the remainder underwent CKC (mean age at surgery 40.8).

The Chinese cohort included 5,050 women; 73.5% underwent LEEP. Mean age at surgery was 40-45.

After 22 years of follow-up in the Swedish cohort, 21.2% of women who underwent LEEP or CKC had recurrence. After 9 years of follow-up in the Chinese cohort, 1.8% of women treated with LEEP had recurrence, while 0.8% of those who underwent CKC had recurrence.

The authors highlighted some limitations to their study, including the target trial emulation design, which ultimately makes the study observational in nature, limiting the generalizability of findings, with room for residual confounding. They also didn’t have data on important factors like smoking, sexual history, partner status, oral contraceptive use, co-infections, or individual-level HPV vaccination status. The Swedish and Chinese cohorts had different follow-up mechanisms, and the Chinese cohort had a shorter follow-up duration, introducing possible follow-up or selection bias.

Yi and team noted that trials with longer follow-up periods are needed to confirm the findings.

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