Histologically verified penile lichen sclerosus-Incidence in Denmark over 26 years and long-term risk of penile and non-penile cancer

Lichen sclerosus (LSc) is a chronic inflammatory disease affecting the anogenital area and having malignant potential. Population-based data on the incidence of LSc in men and associated cancer risk are sparse. In the Danish Pathology Register, we identified all men with histologically verified penile LSc 1997-2022 and calculated incidence rates. Through linkage with the Danish Cancer Registry, standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were computed as relative risk estimates of penile squamous cell carcinoma (SCC) and non-penile cancer in men with penile LSc (1978-2019) compared with background population rates. During the study period, the age-standardized incidence rate of penile LSc more than doubled, being 17.9 per 100,000 person-years in the most recent time (2021-2022). The age-specific incidence increased with age and was highest in ages 70-79 years (29.2 per 100,000 person-years). Compared with the general population, men with penile LSc had an increased rate of penile SCC (SIR = 15.5, 95% CI: 12.0-19.5), which increased with follow-up length and younger age at LSc diagnosis. Rates of non-penile cancers were mostly close to unity except for lung cancer (SIR = 0.6, 95% CI: 0.5-0.7). This nationwide study showed an increased incidence of histologically verified penile LSc over the past 26 years. Importantly, men with penile LSc had nearly 16 times higher rate of penile SCC compared with the general population. There was no strong association with the non-penile cancers, except for a lower rate of lung cancer, suggesting that the malignant potential of LSc is caused by local factors rather than a general cancer predisposition.