Topical therapy and vulvar malignancy risk in lichen sclerosus: a large propensity-matched study

To evaluate the risk of vulvar dysplasia and malignancy in lichen sclerosus patients treated with topical clobetasol or topical calcineurin inhibitors.

This population-level retrospective cohort study used TriNetX, a research database of electronic health records and claims data from United States and European patients. We assessed 55,696 adult lichen sclerosus patients and matched controls to evaluate baseline risk. To analyze treatment effects, 14,430 clobetasol-exposed lichen sclerosus patients were compared with matched corticosteroid-naïve controls. 6227 topical calcineurin inhibitor-exposed patients were similarly matched and compared to unexposed controls. Finally, 7239 clobetasol-exposed patients were directly compared to matched topical calcineurin inhibitor-exposed patients. Risk ratios were calculated to quantify the risk of developing the outcome, and Kaplan-Meier survival analyses with log-rank tests were used to estimate the cumulative probability of outcome occurrence over a defined time interval. Statistical significance was defined as a P value <.05 for all analyses.

Over 10 years, lichen sclerosus was associated with an 11-fold increased risk of vulvar malignancy (risk ratio, 11.08; 95% confidence interval, 8.92-13.76) and an 8-fold increased risk of vulvar dysplasia (risk ratio, 8.04; 95% confidence interval, 6.47-9.98) compared to controls. Clobetasol was associated with a relative overall reduced risk of vulvar malignancy, with a statistically significant risk reduction observed at the 2-year time point (risk ratio, 0.62; 95% confidence interval, 0.42-0.94). Topical calcineurin inhibitor exposure was not associated with an increased risk of vulvar dysplasia or malignancy at any time point. There were no significant differences in the risk of dysplasia or malignancy between patients treated with clobetasol vs topical calcineurin inhibitors.

Lichen sclerosus is associated with a significantly increased risk of vulvar dysplasia and malignancy. In this study, clobetasol appeared to be protective against neoplastic transformation, particularly in early stages of the disease. Topical calcineurin inhibitors were not associated with an increased risk of dysplasia or malignancy.