Topical therapy and vulvar malignancy risk in lichen sclerosus: a large propensity-matched study
Adults with vulvar lichen sclerosus had much higher vulvar precancer and cancer risk; early clobetasol use was linked to a small reduction in cancer at 2 years.
*Retrospective propensity-matched cohort study; Level 2b (OCEBM).
*Retrospective propensity-matched cohort study; Level 2b (OCEBM).
Citation
Adams PE, Vikram EP, Curman P, Kraus CN, Amber KT. Topical therapy and vulvar malignancy risk in lichen sclerosus: a large propensity-matched study. American Journal of Obstetrics & Gynecology. 2026;May. doi:10.1016/j.ajog.2025.12.043.
Background
Vulvar lichen sclerosus is a chronic inflammatory skin condition that can lead to vulvar precancer and cancer. Whether common topical treatments change this risk has been uncertain.
Patients
Adult female patients in a large electronic health record database (United States and Europe) with vulvar lichen sclerosus; required at least 2 recorded diagnoses and at least 10 years of available follow-up. For treatment analyses, patients with solid organ transplant were excluded.
Intervention
Topical clobetasol, or topical calcineurin inhibitors (tacrolimus or pimecrolimus), started after diagnosis.
Control
Matched patients with postmenopausal vaginal thinning/dryness diagnosis (baseline risk analysis), or matched lichen sclerosus patients without the relevant topical exposure (treatment analyses).
Outcome
Vulvar cancer; vulvar dysplasia or vulvar carcinoma in situ.
Follow-up Period
Up to 10 years (with 2-, 5-, and 10-year risk windows).
Results
| Comparison | Time | Absolute risk (treatment vs control) | Risk ratio (95% confidence interval) | NNT/NNH |
|---|---|---|---|---|
| Lichen sclerosus vs control: vulvar cancer (primary) | 10 years | 1.7% vs 0.2% | 11.08 (8.92–13.76) | NNH 67 |
| Lichen sclerosus vs control: vulvar dysplasia/carcinoma in situ | 10 years | 1.3% vs 0.2% | 8.04 (6.47–9.98) | NNH 91 |
| Clobetasol-exposed vs unexposed lichen sclerosus: vulvar cancer (primary) | 2 years | 0.3% vs 0.5% | 0.62 (0.42–0.94) | NNT 500 |
Other clobetasol, calcineurin inhibitor, and head-to-head comparisons were not statistically significant in the main analysis.
Limitations
Retrospective database study; diagnosis and outcomes relied on billing codes, not uniform biopsy confirmation. Treatment dose and adherence were unavailable. Matching used limited patient factors, so confounding is likely. Absolute risk differences were small (for clobetasol at 2 years, about 2 fewer cancers per 1000 patients).
Funding
No funding reported.
Clinical Application
Reinforces early, consistent clobetasol as first-line therapy and supports calcineurin inhibitors as non–cancer-increasing alternatives when needed.
Discussion
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In this propensity-matched retrospective cohort, clobetasol exposure in lichen sclerosus was associated with lower 2-year vulvar malignancy risk (RR 0.62; ~0.3% vs 0.5%). Given residual confounding and inability to prove causality, should this change counseling, treatment urgency, or surveillance? In this retrospective cohort, clobetasol-exposed patients had a 2-year vulvar malignancy risk of about 0.3% versus 0.5% in matched corticosteroid-naïve controls, with RR 0.62. Which interpretation is most appropriate?