Rising incidence and mortality rate of hepatocellular carcinoma in the USA: A comprehensive analysis

Background and Aim

Over the past two decades, there has been a significant increase in the incidence of primary liver cancer in the USA, with higher rates observed in men. Its burden increases with age and disproportionately affects men, with mortality rates three times higher in men than in women. The higher incidence in men can be partially attributed to a greater prevalence of risk factors such as alcohol abuse and chronic HBV and HCV infections. A recent study of the Surveillance Epidemiology and End Results (SEER) database showed rising incidence and mortality of liver cancer in the USA from 1975 to 2017. The most notable increase in incidence was observed in men and older adults. Another study found varying mortality rates of HCC across different age-specific populations in recent years. While mortality rates were found to be decreasing in younger individuals, they were increasing in older adults. In addition, liver cancer trends among racial groups showed increasing incidence and mortality rates from 1975 to 2017, with variations across different race groups.

Given the escalating incidence and mortality of HCC and the observed disparities among age and racial/ethnic groups, analyzing recent trends can aid in identifying high-risk populations, guiding early detection, intervention, and treatment, and ultimately improving patient outcomes. While current literature offers insight into the increasing incidence and mortality rates of HCC, there remains limited data pertaining to recent sex, age, and racial/ethnic group-specific incidence and mortality rates and time trends. This is especially important given the increasing incidence of several gastrointestinal cancers in younger adults, particularly in younger women. Therefore, this study aimed to evaluate recent incidence and mortality rates and time trends of HCC in the USA, focusing on specific sex, age, and race/ethnicity.

Methods

Age-adjusted HCC incidence rates were calculated from the Centers for Disease Control's United States Cancer Statistics database, which combines incidence data on newly diagnosed cancer cases and covers approximately 98% of the population in the USA. Additionally, age-adjusted HCC mortality rates were obtained from the Centers for Disease Control's National Center for Health Statistics database, which offers comprehensive coverage spanning nearly 100% of deaths attributed to HCC in the USA. Rates were stratified by sex, age (older [≥55 years] and younger [<55 years] adults), race and ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian/Pacific Islander, and Non-Hispanic American Indian/Alaska Native), and tumor stage at diagnosis (early and late). Annual and average annual percentage change (AAPC) were calculated using joinpoint regression. A sex-specific pairwise comparison was conducted.

Results

Between 2001 and 2020, there were 467,346 patients diagnosed with HCC (26.0% women), with increasing incidence in both sexes without significant difference (p=0.65). In younger adults (78,169 patients), the incidence decreased in men but not in women (AAPC difference=−2.39, p=0.002). This was seen in various racial and ethnic groups, mostly driven by early-stage tumors (AAPC difference=−2.65, p=0.02). There were 329,973 deaths attributed to HCC between 2000 and 2020 (28.4% women). In younger adults (43,093 deaths), mortality decreased in men at a greater rate than in women (AAPC difference=1.61, p=0.007). This was seen in various racial and ethnic groups, most notably in non-Hispanic American Indian/Alaska Natives (AAPC difference=−4.51, p=0.01).

Conclusions

In conclusion, our nationwide comprehensive analysis of the USCS database, which covers nearly all patients diagnosed with HCC, shows an increasing incidence of HCC rates between 2001 and 2020. Our analysis of younger adults shows decreasing HCC incidence in younger men but not in women. This trend was seen in various racial/ethnic groups, and was mostly attributed to tumors diagnosed at an early stage. Additionally, our evaluation of the NCHS database, which covers nearly all deaths attributed to HCC in the USA, showed increasing HCC mortality between 2000 and 2020. When evaluating younger adults, HCC mortality rates were found to have improved in men at a greater rate compared to women, and this was notable in various racial/ethnic groups, especially in NHAIAN. The reason for the disparity in incidence and mortality between men and women is unclear and may be attributed to known or yet-to-be-discovered modifiable or non-modifiable risk factors that might have been disproportionately affecting younger women. Future studies are warranted to identify the risk factors associated with the occurrence and outcomes of HCC in different populations, especially in younger women.