The study, published in Cancer Causes & Control, drew on the Surveillance, Epidemiology, and End Results (SEER) 12 registry program, which covers approximately twelve percent of the U.S. population and offers continuous population-based incidence data stretching back to 1992. Researchers from Baylor College of Medicine identified 68,023 cases of hepatocellular carcinoma diagnosed between January 1, 1992 and December 31, 2022 among adults aged twenty and older. Rather than simply tracking raw incidence rates, the team focused on incidence rate ratios, or IRRs, which compare the age-adjusted rate in each demographic group against a reference group, women in the sex analysis and non-Hispanic White individuals in the race and ethnicity analysis. This approach isolates relative disparities from absolute incidence, revealing whether the distance between groups is widening or narrowing even when all rates are rising together.

The headline trend is that hepatocellular carcinoma in the United States has passed through an inflection point. Annual case counts climbed from 840 in 1992 to 2,846 in 2022, an increase of nearly 239 percent, and the overall age-adjusted rate rose from 4.27 to 7.84 per 100,000 person-years over the same period. Joinpoint regression, a statistical technique that identifies inflection points in trend data using Monte Carlo permutation testing, showed that incidence rose by 4.72 percent annually from 1992 to 2009, plateaued between 2009 and 2015, and then declined by 3.41 percent per year from 2015 to 2022. This late reversal is significant because earlier forecasts, notably a 2016 projection based on data through 2012, had anticipated continued increases through 2030. The new analysis demonstrates that the anticipated turning point has in fact materialized.

Sex differences remain the most durable feature of liver cancer epidemiology. Men were diagnosed at 12.24 per 100,000 in 2022 compared with 3.95 per 100,000 among women, and the male-to-female incidence rate ratio never dropped below three. Yet the ratio itself declined from 3.29 in 1992 to 3.11 in 2022. The dynamics behind that shift are revealing: from 1992 to 2012 the male-to-female IRR actually increased slightly, by about half a percent per year, before falling by 1.64 percent annually thereafter. The narrowing was driven by steeper declines in male incidence after 2012 rather than any surge in female rates, and the effect was most pronounced among adults under fifty, where the IRR dropped by roughly six percent per year after 2012, though the authors caution that the confidence interval on that age-stratified estimate was wide and warrants cautious interpretation.

The most dramatic change, however, unfolded along racial and ethnic lines. In 1992, non-Hispanic Asian/Pacific Islander individuals were diagnosed with hepatocellular carcinoma at nearly six times the rate of non-Hispanic White individuals, an IRR of 5.86. By 2022 that ratio had fallen to 1.87, an average annual decline of 3.93 percent across the study period. This extraordinary convergence reflects two simultaneous movements: incidence among Asian/Pacific Islander Americans actually declined over the three decades, from about 15.2 to 10.2 per 100,000, while incidence among non-Hispanic White individuals rose from 2.6 to 5.5 per 100,000. The declining IRR therefore captures both good news in one population and rising burden in another, a nuance the authors emphasize repeatedly.

The other relative disparities narrowed more modestly. The non-Hispanic Black-to-non-Hispanic White IRR fell from 2.08 to 1.44, with the most significant decline occurring between 2005 and 2022. The Hispanic-to-non-Hispanic White IRR barely moved, easing from 2.62 to 2.40, an average annual decrease of only 0.57 percent. Across the full study period, incidence remained highest among Asian/Pacific Islander individuals at 14.27 per 100,000, followed by Hispanic individuals at 12.12, non-Hispanic Black individuals at 9.30, and non-Hispanic White individuals at 4.37. Age-stratified analyses added further texture: among adults under fifty, the Black-to-White IRR declined linearly throughout the period, whereas among older adults it first rose by 1.61 percent annually through 2005 before declining by nearly two percent annually thereafter.

What lies behind these shifting ratios? The study cannot establish causation, since SEER registries do not record individual risk factors, but the temporal patterns align strikingly with known changes in the etiology of liver cancer. Hepatitis B virus has long been a dominant driver of hepatocellular carcinoma in Asian and Pacific Islander populations, and the United States added universal infant HBV vaccination to its immunization schedule in 1991, with particularly high uptake among post-1991 birth cohorts and among Asian American children. Because preventing chronic HBV infection in infancy reduces cancer risk only after a long latency, the timing of declining incidence among younger adults in these historically high-prevalence populations is temporally compatible with a vaccination effect, though the authors stress this remains hypothesis-generating rather than proof.

Hepatitis C tells a complementary story. Direct-acting antivirals, which cure HCV infection and thereby interrupt the progression to cirrhosis and cancer, became available in the United States in late 2013 and expanded rapidly through the latter half of the 2010s. The post-2015 decline in overall hepatocellular carcinoma incidence follows this therapeutic revolution closely enough to suggest a genuine contribution, but the variable latency between viral eradication and changes in cancer risk means the association must be interpreted cautiously. Meanwhile, a countervailing force is gathering strength: metabolic dysfunction-associated steatotic liver disease, or MASLD, and diabetes are becoming increasingly dominant drivers of new liver cancer cases, and population-level alcohol consumption and alcohol-associated liver disease mortality have both risen in recent decades. These trends do not explain the recent overall decline and may instead represent a competing influence shaping which groups continue to bear the burden.

The sex-specific narrowing may be an early signal of the metabolic transition. Accumulating evidence suggests that women with diabetes and MASLD may experience a disproportionately greater relative increase in liver-related risk compared with men, and as the prevalence of metabolic disease rises, particularly among younger and middle-aged women, the historical male predominance in liver cancer may continue to attenuate. This would represent a fundamental shift in the epidemiology of a cancer whose sex disparity has been attributed in part to higher rates of viral hepatitis and heavy alcohol use among men.

The study’s authors are careful about what these findings do and do not mean. The narrowing of incidence rate ratios signals attenuation of relative disparities, not their elimination; absolute incidence in 2022 remained substantially higher among men than women and among Asian/Pacific Islander, Hispanic, and Black individuals than among non-Hispanic White individuals. Limitations include the absence of individual-level data on risk factors, the possibility that evolving diagnostic practices and surveillance influenced case ascertainment, potential misclassification of race and ethnicity, and geographic coverage limited to roughly thirteen percent of the U.S. population, excluding regions such as Texas that appear only in newer SEER releases. The team selected SEER 12 over the broader SEER 21 database precisely because it extends back to 1992, enabling a genuinely long-term view. Still, the message for public health is clear: vaccination, antiviral therapy, and early detection have visibly reshaped who gets liver cancer in America, but continued efforts to prevent, detect, and manage both viral and metabolic liver disease are needed to close the remaining gaps.

Subject of Research: Temporal trends in sex and racial/ethnic disparities in hepatocellular carcinoma incidence in the United States from 1992 to 2022

Article Title: Temporal changes in sex and race/ethnicity incidence rate ratios for hepatocellular carcinoma in the United States, 1992–2022

Article References: Temporal changes in sex and race/ethnicity incidence rate ratios for hepatocellular carcinoma in the United States, 1992–2022. (n.d.). https://doi.org/10.1007/s10552-026-02238-w

Image Credits: AI Generated

DOI: 10.1007/s10552-026-02238-w

Keywords: hepatocellular carcinoma, liver cancer, incidence rate ratios, health disparities, SEER, hepatitis B, hepatitis C, MASLD, sex differences, race and ethnicity, cancer epidemiology, Cancer Causes & Control