Sex Differences in Birth Cohort Effects for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) is rising more rapidly than melanoma across many high-risk populations, but the drivers of this divergence are incompletely understood. cSCC risk is strongly related to cumulative lifetime ultraviolet (UV) radiation exposure in a dose-dependent manner; if so, generational shifts in sun exposure may manifest as birth cohort effects. OBJECTIVE: To examine birth cohort effects in cSCC incidence across seven high-risk populations, using melanoma as a comparator, and to determine whether cohort effects differ by sex. METHODS: We conducted age-period-cohort (APC) modelling of cSCC and invasive melanoma incidence using cancer registry data from Norway, Sweden, Finland, Denmark, Scotland, the Netherlands, and Tasmania, Australia (1989-2020). Cohort rate ratios, describing incidence relative to a 1959 reference cohort and adjusted for age and period effects, as well as period rate ratios and longitudinal age curves were examined separately by sex. RESULTS: We observed a progressive increase in cohort-specific cSCC risk across successive birth cohorts in both sexes and most populations. The increase was substantially greater in women than in men in five of seven populations, most pronounced in Tasmania, Norway, Denmark, Sweden, and the Netherlands, and was present in pre-1959 birth cohorts. In contrast, melanoma cohort effects were broadly similar between sexes, with male effects, if anything, larger in several populations. CONCLUSIONS: Rising cSCC incidence has a substantial and potentially modifiable behavioural component, driven by generational increases in cumulative UV exposure that have disproportionately affected women. Reducing lifetime sun exposure, particularly in high ambient UV environments, could meaningfully reduce the future burden of cSCC.