Global trends and inequities in childhood cancer burden from 1990 to 2021, with projections to 2040: a Global Burden of Disease study.
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BACKGROUND: Childhood cancer now accounts for a substantial and growing share of global pediatric mortality and disability as infectious and nutritional disease burdens have fallen. We aimed to quantify global, regional, and sociodemographic patterns in childhood cancer incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021, and to project these trends to 2040. METHODS: We conducted a global observational analysis using GBD 2021 estimates for children aged 0-14 years across 204 countries and territories. Annual incident cases, deaths, incidence rates, mortality rates, and DALY rates were extracted by cancer type, sex, age group, and Socio-Demographic Index (SDI) quintile. Temporal trends were summarized by percentage change from 1990 to 2021 and estimated annual percentage change (EAPC). Correlations between SDI and burden measures/EAPC were assessed via Pearson coefficients. Bayesian age-period-cohort models projected incidence and mortality through 2040. RESULTS: In 2021, an estimated 185 530 (95% UI 154 650-216 210) childhood cancer cases and 83 020 (69 000-96 870) deaths occurred globally, corresponding to incidence 9.22 (7.69-10.75) and mortality 4.13 (3.43-4.81) per 100 000. From 1990 to 2021, global incident counts declined by 11.92% (-28.85% to + 10.24%) and incidence rate by 23.86% (-38.50% to -4.70%); deaths fell by 39.02% (-50.80% to -22.87%) and mortality by 47.29% (-57.47% to -33.32%). Leukemia, brain, and central nervous system tumors and non-Hodgkin lymphoma remained predominant. High-SDI countries saw the greatest reductions in incidence, whereas several low-SDI regions experienced stable or rising mortality. SDI positively correlated with incidence [rs = 0.41, 95% confidence interval (CI), 0.28 to 0.54] and negatively with mortality EAPC (rs = -0.30, 95%CI, -0.72 to -0.55). Projections to 2040 indicate further declines under current trajectories. CONCLUSIONS: Despite global improvements, profound inequities in childhood cancer burden persist, driven by under-diagnosis and limited access to care in low-SDI settings. Achieving the WHO target of ≥60% survival by 2030 will require urgent investments in diagnostic capacity, treatment access, workforce training, and integration of childhood cancer into universal health coverage. Failure to act risks leaving the world's poorest children behind.