Risk of esophageal adenocarcinoma after Helicobacter pylori eradication treatment in a population-based multinational cohort study

Background & Aims Helicobacter pylori infection is associated with a decreased risk of esophageal adenocarcinoma, and the declining prevalence of such infection might contribute to the rising incidence of this tumor. We examined the hypothesis that eradication treatment of Helicobacter pylori increases the risk of esophageal adenocarcinoma. Methods This population-based multinational cohort, entitled the “Nordic Helicobacter Pylori Eradication Project (NordHePEP)”, included all adults (≥18 years) receiving Helicobacter pylori eradication treatment from 1995-2018 in any of the five Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) with follow-up throughout 2019. Data came from national registers. We calculated standardized incidence ratios (SIR) with 95% confidence intervals (CI) by dividing the cancer incidence in the exposed cohort by that of the entire Nordic background populations of the corresponding age, sex, calendar period, and country. Analyses were stratified by factors associated with esophageal adenocarcinoma, i.e., education, comorbidity, gastroesophageal reflux, and certain medications. Results Among 661,987 participants who contributed 5,495,552 person-years after eradication treatment (median follow-up 7.8 years, range 1-24 years), 550 cases of esophageal adenocarcinoma developed. The overall SIR of esophageal adenocarcinoma was not increased (SIR=0.89, 95% CI 0.82-0.97). The SIR did not increase over time after eradication treatment, but rather decreased and was 0.73 (95% CI 0.61-0.86) 11-24 years after treatment. There were no major differences in the stratified analyses. The overall SIR of esophageal squamous cell carcinoma, calculated for comparison, showed no association (SIR=0.99, 95% CI 0.89-1.11). Conclusion This absence on an increased risk of esophageal adenocarcinoma after eradication treatment of Helicobacter pylori suggests eradication is safe from a cancer perspective.