Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001-2020
Authors: Arnett Azlann , Siegel David A. , Dai Shifan , Thompson Trevor D. , Foster Jennifer , di Pierro Erika J. , Momin Behnoosh , Lupo Philip J. , Heczey Andras 
Published: March 2024

ABSTRACTImportanceHepatocellular carcinoma accounts for approximately 80% of liver neoplasms. Globally, hepatocellular carcinoma ranks as the third most lethal cancer, with the number of deaths expected to further increase by 2040. In adults, disparities in incidence and survival are well described while pediatric epidemiology is not well characterized.ObjectiveTo describe incidence and survival for pediatric (ages 0-19 years) hepatocellular carcinoma cases and compare these measures to adults (ages ≥20 years) diagnosed with hepatocellular carcinoma. We evaluated demographic factors and clinical characteristics that influence incidence and outcomes.DesignPopulation-based cohort study.SettingIncidence data from the US Cancer Statistics database from 2003 to 2020 and 5-year relative survival from the National Program of Cancer Registries from 2001 to 2019, covering 97% and 83% of the US population, respectively.Participants355,349 US Cancer Statistics and 257,406 the National Program of Cancer Registries patients were identified using ICD-O-3 C22.0 and 8170-5 codes.Main Outcomes and MeasuresIncidence annual percent change (APC) and average APC (AAPC) using joinpoint regression. Five-year relative survival. All-cause survival estimated using multivariate Cox modeling. Corresponding 95% confidence intervals (CI) were calculated.ResultsIncidence rate per 100,000 persons was 0.056 (95%CI:0.052-0.060) for pediatric cases and 7.793 (7.767-7.819) for adults. Incidence was stable in the pediatric population (0.3 AAPC, −1.1-1.7). In contrast, after periods of increase, incidence declined in adults after 2015 (−1.5 APC). Relative survival increased over time for both pediatric and adult ages and was higher for children and adolescents (46.4%, 95%CI:42.4-50.3) than adults (20.7%, 95%CI:20.5-20.9) overall and when stratified by stage. Regression modeling showed that non-Hispanic Black race and ethnicity was associated with higher risk of death in children and adolescents (1.48, 95%CI:1.07-2.05) and adults (1.11, 95%CI:1.09-1.12) compared to non-Hispanic white race and ethnicity.Conclusions and RelevanceBetween 2003 and 2020 in the United States, pediatric incidence was stable while incidence in adults began to decline after 2015. Survival was higher across all stages for children and adolescents compared to adults. Non-Hispanic Black race and ethnicity showed a higher risk of death for both age groups. Further studies could explore the factors that influence these outcome disparities.KEY POINTSQuestionHow does incidence and survival compare between pediatric and adult hepatocellular carcinoma (HCC)?FindingsIn contrast to adults, pediatric incidence rates of HCC were stable, and no demographic risk factors for incidence were identified. Pediatric HCC survival was higher than adults. Non-Hispanic Black race and ethnicity, small metropolitan county, and non-fibrolamellar histology, were risk factors in both pediatric and adult groups.MeaningNon-Hispanic Black patients and those living in smaller metropolitan and non-metropolitan areas irrespective of age might benefit from further research in outcome disparities, provider education, and prospective studies to maximize outcomes through effective risk-adapted management strategies.