Sex and race disparities in the incidence of hepatocellular carcinoma in the United States examined through age–period–cohort analysis

Background: Incidence rates for hepatocellular carcinoma (HCC) vary considerably by age, sex, and race/ethnicity. We assessed whether the underlying reasons for variations in HCC among subgroups of the population by age, sex, race/ethnicity, and birth cohort are uniform or whether they interact with one another or have changed over time. Methods: Data were from the U.S. Cancer Statistics registry. We assessed annual trends within population subgroups and examined for secular trends in the male-to-female ratio for HCC incidence. We used joinpoint regression to compute annual percent change and average annual percent change (AAPC) and corresponding 95% confidence intervals (CI). We also used age–period–cohort models to disentangle period and cohort effects. Results: Between 2001 and 2015, HCC rates increased in men and women ≥50 years, remained stable among women ages 40 to 49 years, but decreased among males ages 40 to 44 years (AAPC ¼ -2.47%; 95% CI, -3.15% to -1.80%) and 45 to 49 years (AAPC ¼ -3.49%; 95% CI, -4.78% to -2.17%). As a result, the male-to-female incidence rate ratio (IRR) among persons aged <50 years decreased from 4.63 in 2001 to 2.42 in 2015 but remained stable over time among persons aged ≥50 years. HCC rates were lower among successive cohorts of males born after circa 1956, whereas HCC rates among females born circa 1991 were higher than those among females born circa 1956 (IRR ¼ 1.67; 95% CI, 1.05–2.65). Conclusions: As a result of decreasing incidence among males aged <50 years and strong cohort effect, the epidemiology of HCC is changing from a disease with striking male predominance to one with less male predominance. Impact: The sex and racial disparities and strong birth cohort effect on HCC risk identified in this study have important implications for population-based HCC prevention efforts.