Hepatopancreatobiliary cancers worldwide, 1990–2021, and projections to 2035: incidence, mortality, inequalities, and risk attribution

Objectives This study aims to characterize global patterns and temporal trends in incidence and mortality, inequalities, risk-attributable mortality, and projected changes through 2035 for hepatopancreatobiliary (HPB) cancers. Methods Using model-based estimates from the Global Burden of Disease (GBD) 2021 study, we assessed liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer (GBTC) by location, age, sex, and socio-demographic index (SDI). Age-standardized incidence and death rates were summarized with 95 % uncertainty intervals (UIs). We examined temporal trends from 1990 to 2021, SDI-related inequalities, and risk-attributable mortality, and projected future rates to 2035. Results In 2021, liver cancer accounted for 529,202 incident cases (95 % UI: 480,339–593,849) and 483,875 deaths (95 % UI: 440,400–540,177); pancreatic cancer for 508,533 cases (95 % UI: 462,091–547,208) and 505,752 deaths (95 % UI: 461,224–543,899); and GBTC for 216,768 cases (95 % UI: 181,888–245,238) and 171,961 deaths (95 % UI: 142,352–194,238). Over 1990–2021, liver cancer incidence was broadly stable while mortality declined modestly, pancreatic cancer increased in both incidence and mortality, and GBTC declined in both measures. Marked geographic and SDI-related heterogeneity was observed. Risk-attributable patterns differed by cancer site and sex, with behavioural risks predominating for liver cancer, metabolic risks – particularly high fasting plasma glucose – for pancreatic cancer, and high body-mass index for GBTC. Conclusions HPB cancers show substantial geographic and sociodemographic variation in incidence and mortality, with distinct site-specific prevention priorities. These findings support more tailored strategies for risk reduction, earlier detection, and resource allocation.