Differences in Hepatocellular Carcinoma Incidence Trends Across US Census Divisions, 2001 to 2021

<b>Background/Objectives:</b> Hepatocellular carcinoma (HCC) is a leading cause of cancer diagnoses and deaths in the United States. This study serves as an update on secular trends in national HCC incidence rates while exploring potential geographic and racial/ethnic differences across all nine US census divisions. <b>Methods</b>: We analyzed HCC incidence data reported to the United States Cancer Statistics (USCS) database from 2001 to 2021 (excluding 2020 data, based on the Centers for Disease Control and Prevention's cautionary recommendations for COVID-19 pandemic data usage for trend analysis). We performed trend analyses of age-adjusted incidence rates in the US overall, by census divisions, and then stratified by race/ethnicity, using the National Cancer Institute's Joinpoint Regression Program. <b>Results</b>: Between 2001 and 2021, HCC incidence rates increased nationally, with an average annual percentage change (AAPC) of 2.51 (95% confidence interval (CI): 2.32-2.72); however, the rate decreased (annual percentage change (APC) -3.33 (95% CI: -4.78--1.96) in recent years from 2018 to 2021. Division 1 had the greatest decrease (APC -6.46 (95% CI: -9.62--3.96) from 2017 to 2021, while rates leveled in Division 6 (East South Central) and Division 7 (West South Central). HCC trends decreased substantially for non-Hispanic Black and Non-Hispanic Asian and Pacific Islander groups in almost all divisions in recent years, but trends were stable, decreased, or increased for other racial/ethnic populations. <b>Conclusions</b>: Despite declining national HCC incidence rates, these trends were not uniform across racial/ethnic groups or US census divisions. Race-specific interventions are needed to reduce disparities in HCC incidence in all US census divisions.