Divergent Trends in Esophageal Adenocarcinoma and Squamous Cell Carcinoma Incidence, 2000–2022

Background: Esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) follow divergent incidence trajectories in the United States. Rising use of electronic nicotine delivery systems (ENDS) and evolving demographic risk profiles may be reshaping these trends. We aimed to characterize national incidence patterns of EAC and ESCC from 2000 through 2022—stratified by age, sex, and race/ethnicity—and to place these in the context of changing behavioral exposures. Methods: We performed a retrospective cohort study using Surveillance, Epidemiology, and End Results SEER 21 registry data (covering 48% of the U.S. population). We included first-primary, histologically confirmed EAC (ICD-O-3 codes 8140–8576) and ESCC (8050–8084) in individuals aged ≥ 15 years diagnosed between 2000 and 2022. Age-adjusted incidence rates (per 100,000 person-years; 2000 U.S. standard) and annual percent changes (APCs) were estimated via Joinpoint regression models. Results: A total of 90,290 EAC and 47,916 ESCC cases were identified. EAC incidence increased from 2.3 to 2.8 per 100,000 (APC +0.90%; 95% CI, 0.45–1.35), with the largest relative rises in ages 15–39 years (APC +1.50%) and among women (APC +2.65%). Non-Hispanic Black and American Indian/Alaska Native populations experienced the most pronounced EAC increases. Overall ESCC incidence declined (APC −0.78%; 95% CI, −1.10 to −0.46), though Asian/Pacific Islander (+3.59%) and American Indian/Alaska Native (+1.58%) groups saw rising rates. Conclusions: EAC incidence continues to climb—especially in younger adults, women, and select racial/ethnic minorities—while ESCC declines are uneven. These histology-specific patterns highlight the urgency of tailored prevention, targeted early-detection efforts, and mechanistic studies on emerging exposures such as vaping.