Importance: Although hepatocellular carcinoma (HCC) incidence has decreased in the US, it is unclear if rural residents have experienced similar trends. Objective: To examine rural-urban differences in HCC incidence and incidence-based mortality trends by sex, race and ethnicity, and stage at diagnosis. Design, Setting, and Participants: This cohort study analyzed HCC diagnoses from 2001 to 2022 and deaths from 2007 to 2022 using data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results (SEER) programs for incidence and the SEER-21 program for incidence-based mortality. Rurality was classified using the 2013 Rural-Urban Continuum Codes. All analyses were performed from October 2025 to February 2026. Main Outcomes and Measures: Annual incidence and incidence-based mortality rates per 100 000 people were calculated and age standardized to the 2000 US standard population. The annual percentage change (APC) and the average APC in incidence and incidence-based mortality rates were then estimated using Joinpoint regression. Results: The study analyzed 264 633 HCC cases (77.0% among men and 86.6% in urban areas). Among men, HCC incidence was 4.5 (95% CI, 4.4-4.5) per 100 000 people in rural counties and 5.8 (95% CI, 5.8-5.8) per 100 000 people in urban counties; among women, HCC incidence was 1.2 (95% CI, 1.2-1.2) per 100 000 people in rural counties and 1.5 (95% CI, 1.5-1.5) per 100 000 people in urban counties. In rural counties, HCC incidence increased by 1.1% (95% CI, 0.6%-1.6%) per year among men from 2007 to 2022 and 1.7% (95% CI, 1.2%-2.3%) per year among women from 2001 to 2022, whereas in urban counties, HCC rates decreased by 1.4% (95% CI, -1.7% to -1.1%) per year among men from 2008 to 2022 and by 1.0% (95% CI, -1.4% to -0.6%) per year among women from 2009 to 2022. Among men, incidence-based mortality rates were 2.7 (95% CI, 2.3-3.0) per 100 000 people in rural counties and 3.8 (95% CI, 3.6-3.9) per 100 000 people in urban counties; among women, the incidence-based mortality rates were 0.8 (95% CI, 0.6-0.9) per 100 000 people in rural counties and 0.9 (95% CI, 0.8-1.0) per 100 000 people in urban counties. In rural counties, incidence-based mortality rates increased by 1.2% (95% CI, 0.3%-2.1%) per year among men and remained stable among women (APC, 0.3% 95% CI, -1.1% to 1.7%), whereas in urban counties, incidence-based mortality rates decreased by 1.4% per year (95% CI, -1.7% to -1.1%) among men and 1.0% (95% CI, -1.7% to -0.4%) per year among women. Conclusions and Relevance: This cohort study revealed rural-urban disparities in HCC incidence and incidence-based mortality trends. These findings highlight the need for targeted prevention strategies and improved access to early detection and specialty care for rural populations.
Damgacioglu et al. (2026) studied this question.