Contemporary Changes in Global Trends in Early-Onset Cancer: Incidence and Mortality (2000–2021)

<b>Background/Objectives:</b> The burden of early-onset cancer (cancer incidence <50 years) has increased globally. Early-onset cancer carries significant societal and economic consequences. We aim to provide updated estimates for incidence and mortality of early-onset cancer. <b>Methods:</b> We analyzed the Global Burden of Disease Study 2021 to describe the incidence, death, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR) from early-onset cancer (i.e., cancer in people aged 15-49), and its changes from 2000 to 2021 (reflected as annual percent change [APC]), using Joinpoint regression analysis. <b>Results:</b> In 2021, there were 3.16 million new cases and 989,650 deaths from early-onset cancer. From 2000 to 2021, the ASIR of early-onset cancer increased (APC: 0.40%, 95% CI 0.32 to 0.47%), with the highest increase observed in the Eastern Mediterranean region (APC: 1.63%, 95% CI 1.53 to 1.72%), whereas the ASDR decreased across most regions. The ASIR for early-onset cancer had a higher increase in females (APC: 0.62%, 95% CI 0.51 to 0.73%) than males (APC: 0.14%, 95% CI 0.04 to 0.23%). Breast cancer (<i>n</i> = 567,900) constituted the highest burden of incident cases, followed by non-melanoma skin (<i>n</i> = 507,810) and cervical cancers (n = 307,430). The highest increase in the ASIR was observed in non-melanoma skin cancer (APC:2.18%, 95% CI 1.85-2.51%), thyroid (APC: 1.70%, 95% CI 1.60 to 1.79%), and testicular (APC:1.37%, 95% CI 0.96 to 1.78%) cancers. The greatest increases in the ASDR were observed in peripheral nervous system cancer (APC: 0.97%, 95% CI 0.82 to 1.11%) and multiple myeloma (APC: 0.62%, 95% CI 0.51 to 0.72%). <b>Conclusions:</b> From 2000 to 2021, the age-adjusted incidence of early-onset cancer increased, with variation across regions and cancer types. Immediate measures are required at a global, regional, and national level to mitigate the burden of early-onset cancer.