Trends in incidence rates of hepatocellular carcinoma and stage at diagnosis by demographics in the U.S. from 2004 to 2021: a joinpoint analysis of the SEER database.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the 13th most common cancer in the U.S., causing approximately 30,000 deaths annually. Incidence has risen substantially over recent decades. This study examines trends in age-adjusted HCC incidence from 2004 to 2021.

MATERIALS AND METHODS: Incidence data for HCC (ICD-10 C22.0) from 2004 to 2021 were obtained from the Surveillance, Epidemiology and End Results (SEER) registry, representing 48% of the U.S. population. Rates were age-adjusted to the 2000 U.S. standard population and stratified by sex, race/ethnicity, age, and stage at diagnosis. Annual percentage changes (APCs) were calculated using Joinpoint regression with statistical significance set at p < 0.05.

RESULTS AND CONCLUSION: From 2004 to 2015, overall HCC incidence increased (APC 3.16; p < 0.01), followed by a significant decline from 2015 to 2021 (APC -1.24; p < 0.01). Racial/ethnic subgroup trends varied: Hispanics, Non-Hispanic Blacks, and American Indian/Alaska Native populations showed rising incidence until 2015 with subsequent declines, while changes among Non-Hispanic Whites were less pronounced. After 2015, incidence declined among females (APC -0.27) and males (APC -1.85). Age-specific trends showed decreasing rates among individuals aged 35-49 and 50-64 years, with declines in those 65+ beginning in 2019. Localized-stage HCC incidence decreased after 2015, while regional trends fluctuated and distant-stage incidence continued to rise. Stage-specific patterns also differed by race. HCC incidence has declined overall since 2015, potentially reflecting improved hepatitis C therapy and risk-factor management. However, persistent or rising rates in specific demographic groups and increasing distant-stage diagnoses highlight ongoing disparities and the need for enhanced screening and early detection strategies.