S999 Divergent Trends in Esophageal Adenocarcinoma and Squamous Cell Carcinoma Incidence in the United States, 2000-2022

Introduction: Esophageal adenocarcinoma (EAC) incidence has risen steeply in Western populations, whereas esophageal squamous cell carcinoma (ESCC) has declined in parallel with falling cigarette smoking. Emerging exposures—especially electronic nicotine delivery systems (ENDS, “vaping”)—may be reshaping esophageal cancer risk. Methods: We conducted a retrospective cohort analysis of Surveillance, Epidemiology, and End Results-21 registry data (2000-2022), including 90,290 EAC and 47,916 ESCC cases. Incidence rates (age-adjusted to the 2000 U.S. standard) were stratified by age, sex, and race/ethnicity. Joinpoint regression estimated annual percent changes (APCs) with 95% confidence intervals (CIs). National cigarette smoking and vaping prevalence trends (2011-2021) were overlaid for contextual interpretation. Results: EAC incidence rose from 2.3 to 2.8 per 100,000 (APC 0.90%; 0.45-1.35; P < .001), with the greatest increases in ages 65-74 years (3.95%; 3.68-4.22), ≥75 years (2.30%; 1.90-2.70), and 15-39 years (1.50%; 0.37-2.64). Female APC (2.65%; 2.42-2.88) exceeded male (2.51%; 2.14-2.87; P < .001). Black (6.54%; 5.46-7.64) and American Indian/Alaska Native (5.39%; 4.78-5.99) populations saw the largest EAC increases. ESCC declined from 1.9 to 1.1 per 100,000 (APC -0.78%; -1.02 to -0.54; P < .001), with steeper falls in Black (-2.17%; -2.38 to -1.96) and White (-0.40%; -0.68 to -0.11) persons, but rising trends in Asian/Pacific Islander (3.59%; 3.02-4.15) and American Indian/Alaska Native (1.58%; 1.12-2.05) groups. Over the same period, adult smoking declined from ∼21% to ∼14% and vaping rose from ∼1% to ∼4.5%. Conclusion: EAC’s continued rise—especially among younger adults, women, and racial minorities—occurs amid surging vaping and persistent obesity/ gastroesophageal reflux disease, implicating novel inhalational exposures. ESCC’s decline mirrors smoking reductions but unevenly across subgroups. Histology-specific, exposure-aware prevention strategies are urgently needed.