Spatiotemporal co-occurrence patterns and related risk factors of esophageal and lip and oral cavity cancers among older adults across 203 countries and territories: a machine learning-driven systematic analysis

BACKGROUND: The country-level co-burden of esophageal cancer and lip and oral cavity cancer (LOC) among older adults remains poorly characterised. We examined global spatiotemporal patterns and associated population-level exposures. MATERIALS AND METHODS: We analyzed Global Burden of Disease 2021 data for adults ≥ 55 years across 203 countries and territories. Incidence rates were classified into quartile-based co-burden categories, comparing 1990-2021 trends with Socio-demographic Index (SDI) trajectories. After screening 58 candidate exposures, random forests and SHapley Additive exPlanations ranked 36. Following variance inflation factor screening, the top 25 entered multivariable negative binomial models with population offsets. RESULTS: =69). Increasing SDI generally coincided with declining esophageal cancer incidence, whereas LOC incidence increased in several high-SDI settings. Both cancers were associated with high alcohol use (esophageal RR=1.32, 95% CI: 1.13-1.53; LOC RR=1.27, 95% CI: 1.13-1.43) and diets low in nuts and seeds (esophageal RR=1.16, 95% CI: 1.05-1.27; LOC RR=1.08, 95% CI: 1.01-1.16). Esophageal cancer was additionally associated with iron deficiency (RR=1.31, 95% CI: 1.14-1.52), occupational exposure to particulate matter, gases, and fumes(RR=1.29, 95% CI: 1.13-1.49), and high red meat diets (RR=1.16, 95% CI: 1.02-1.33). LOC was associated with chewing tobacco (RR=1.32, 95% CI: 1.22-1.44) and high-sodium diets (RR=1.10, 95% CI: 1.01-1.20). CONCLUSIONS: These ecological associations indicate geographic heterogeneity in cancer co-burden and exposure profiles, informing regionally tailored prevention priorities without establishing individual-level causality.