Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies. AYA cancer, defined as cancer occurring in individuals aged 15-39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC). In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: - 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: - 1.64), but the decline slowed from 2012 (AAPC: - 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI. AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.
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