Screening for Helicobacter pylori to Prevent Gastric Cancer: A Pragmatic Randomized Clinical Trial

Importance: Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. Objective: To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. Design, Setting, and Participants: A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. Intervention: Invitation for testing for H pylori stool antigen. Main Outcomes and Measures: The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. Results: Of 240000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63508 were invited for HPSA + FIT, and 88995 were invited for FIT alone. Of the 240000 randomized, 38792 who were unreachable and 48705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31497/63508) for HPSA + FIT and 35.7% (31777/88995) for FIT alone. Among 12142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P =.23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P =.57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). Conclusions and Relevance: Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. Trial Registration: ClinicalTrials.gov Identifier: NCT01741363.