Evolving patterns and cohort-specific risks of anal cancer mortality in Spain

Anal cancer, though rare, is rising in high-income countries, yet long-term national data from Spain remain limited. This study evaluates 25-year trends and cohort-specific mortality risks.

Anal cancer deaths from 1999-2023 were obtained from the Spanish National Institute of Statistics. Age-standardized mortality rates (ASMRs) were calculated using the 2013 European standard population. Joinpoint regression identified temporal trends, while age-period-cohort modelling disentangled age, period, and birth cohort effects.

Among 2,549 deaths, overall ASMRs increased steadily in men (AAPC = 2.8%, 95% CI: 1.8;3.8). Women's rates remained lower, ranging from 0.20 to 0.25 per 100,000, with an AAPC of 1.0% (95% CI: -1.1;3.2). Women showed biphasic patterns: stable rates 1999-2009 (APC = -2.2%), then significant acceleration post-2009 (APC = 3.5%). Mortality was concentrated in adults ≥50 years, where rates increased from 0.54 to 1.01 per 100,000 in men and 0.54 to 0.63 per 100,000 in women. Rates in those <50 years remained extremely low (<0.06 per 100,000), with declining trends in men after 2012. Age-period-cohort analysis revealed strong cohort effects, with peak mortality risk in the 1964 birth cohort (RR = 1.95 in men; RR = 1.94 in women vs. 1954 cohort). Local drift analysis showed maximum annual increases at ages 55-59 years.

Anal cancer mortality in Spain has risen substantially, driven by birth cohort effects concentrated in adults ≥50 years. Elevated risks in post-1949 cohorts likely reflect increased HPV exposure. Urgently needed are expanded gender-neutral HPV vaccination and targeted screening for high-risk populations.