Effect of thermal ablation on persistent HPV infection in Danish women ≥ 40 years of age: a quasi-randomized clinical study

Abstract

Thermal ablation is a cervical heat treatment that destroys a defined area of the cervix. We evaluated whether thermal ablation facilitates HPV clearance in women with persistent high-risk human papillomavirus (HR-HPV) infection, using HPV status and FAM19A4/miR124-2 DNA methylation as molecular markers for treatment efficacy. A total of 131 women aged ≥ 40 years with persistent HR-HPV infection but without histologically confirmed high-grade cervical intraepithelial neoplasia (≥ CIN2) were enrolled at three outpatient gynecological clinics. After exclusions, 39 women were allocated to the intervention arm (thermal ablation) and 34 to the no treatment only control arm. Allocation was based on date of birth (even dates: intervention; odd dates: control), using quasi-randomization. HPV genotyping and FAM19A4/miR124-2 methylation status were assessed at baseline (0 months), 3 months, and 10 months. Thermal ablation was performed using the WISAP probe at 65 °C for 2 min and at 100 °C for 40 s, administered across two sessions 2–3 days apart. At 10 months, 64.1% of women in the intervention arm and 79.4% in the control arm remained HR-HPV positive. No significant difference in HPV positivity was observed between arms at any time point. FAM19A4/miR124-2 methylation positivity showed a transient decrease in the intervention arm (-10.2%) at 3 months but increased in both arms over 10 months to above baseline levels, with no significant treatment effect. Thermal ablation does not facilitate HPV clearance in women with persistent HR-HPV infection without significant cervical disease. Methylation positivity increased over time in both study arms, consistent with ongoing oncogenic transformation. Women treated with thermal ablation remain HR-HPV positive and require continued surveillance, indicating no clinical benefit over observation alone. ClinicalTrials.gov, NCT07376031, registered 21 January 2026. Thermal ablation does not significantly affect HPV clearance or FAM19A4/miR124-2 methylation status in women ≥40 years with persistent high-risk HPV infection without significant cervical disease.