TOPLINE:

Vulvar lichen sclerosus (LS) is associated with an 11-fold increased risk for vulvar malignancy and an eightfold increased risk for vulvar dysplasia in patients compared with control individuals. Clobetasol reduces vulvar malignancy risk by more than one third at 2 years after diagnosis. Topical calcineurin inhibitors (TCIs) do not increase malignancy risk.

METHODOLOGY:

• Researchers conducted a population-level retrospective cohort study using TriNetX, a research database of electronic health records and claims data from patients in the US and Europe, with data retrieved between May and November 2025 from up to 71 healthcare organizations.
• A total of 55,696 adult patients with LS and matched control individuals were assessed to evaluate baseline risk; 14,430 clobetasol-exposed LS patients were compared with matched corticosteroid-naive control individuals; 6227 TCI-exposed patients were matched and compared to unexposed control individuals; and 7239 clobetasol-exposed patients were directly compared to matched TCI-exposed patients.
• Patients were required to have at least two separate documented occurrences of the International Classification of Diseases, 10th Revision, codes (ICD-10) L90.0 for LS or N95 for postmenopausal atrophic vaginitis within the past 10 years, with ≥ 10 years of available follow-up data from the date of first recorded diagnosis encounter.
• Risk ratios (RRs) were calculated to quantify differences in the risk for developing the outcome, and Kaplan-Meier survival analyses with log-rank tests were used to estimate the cumulative probability of occurrence over a defined time interval at 2, 5, and 10 years.

TAKEAWAY:

• Over 10 years, patients with LS had an 11-fold increased risk for vulvar malignancy (RR, 11.08; 95% CI, 8.92-13.76) and an eightfold greater risk for vulvar dysplasia (RR, 8.04; 95% CI, 6.47-9.98) than control individuals.
• Clobetasol exposure was associated with a statistically significant reduction in vulvar malignancy risk at the 2-year timepoint (RR, 0.62; 95% CI, 0.42-0.94), although no significant differences were observed at the 5-year or 10-year timepoints.
• TCI exposure was not associated with an increased risk for vulvar dysplasia or malignancy at any timepoint (2, 5, or 10 years) in the primary analysis.
• No significant differences in the risk for vulvar dysplasia or malignancy were observed when comparing clobetasol to TCIs directly in the primary analysis, although sensitivity analysis with additional covariates suggested clobetasol modestly reduced the risk.

IN PRACTICE:

“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 the early stages of the disease. Topical calcineurin inhibitors were not associated with an increased risk of dysplasia or malignancy,” the authors of the study wrote.

SOURCE:

The study was led by Paige E. Adams and Kyle T. Amber, MD, both from the Rush University Medical Center Department of Dermatology in Chicago. It was published online in American Journal of Obstetrics & Gynecology.

LIMITATIONS:

Individual-level variables such as disease severity, patient-specific risk factors, human papillomavirus status, and treatment adherence were not available in the database. Reliance on ICD-10 codes may confer misclassification bias, although researchers attempted to mitigate this by requiring two instances of LS diagnosis for inclusion. The absence of specific ICD-10 codes for vulvar LS and differentiated vulvar intraepithelial neoplasia further complicates case ascertainment. Data on treatment dosage, frequency, or duration were unavailable in TriNetX, limiting the assessment of therapeutic exposure. The platform also does not distinguish between systemic and topical tacrolimus, and inadvertent inclusion of systemic exposure may have occurred despite exclusion of transplant recipients. The variability in healthcare organization data availability on TriNetX may influence cohort composition and risk estimates between analyses. Residual confounding may persist despite propensity score matching, and patients receiving care outside the TriNetX network were not captured.

DISCLOSURES:

The study received no funding. Adams and Ellee Pisey Vikram have no disclosures. Christina N. Kraus is the recipient of a Dermatology Foundation Career Development Award and has been a consultant for Nuvig Therapeutics and LEO Pharma, and an investigator for Incyte Corporation. Philip Curman has participated in studies that received funding from Sanofi and Novartis. Amber reported receiving research support from Argenx, AstraZeneca, KabaFusion, and Sanofi.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.