Background
The Republic of Korea has historically borne a high burden of gastric cancer, although substantial epidemiological transitions have occurred over recent decades. Gastric cancer was the most commonly occurring cancer in Korea until 2018, but declined to fifth by 2022. Gastric cancer incidence has decreased steadily, accompanied by marked reductions in mortality and substantial improvements in survival, with 5-year overall survival now exceeding 75%. During this period, the seroprevalence of Helicobacter pylori (H. pylori) has shown a decreasing trend, with the most pronounced reductions observed in younger generations. Randomized controlled trials conducted in high-risk groups, including patients after endoscopic resection for early gastric cancer and first-degree relatives of gastric cancer patients, have demonstrated that H. pylori eradication significantly reduces gastric cancer risk.
Objectives
To further evaluate the role of H. pylori eradication as a primary prevention strategy in the general population, a large-scale randomized clinical trial, the Helicobacter pylori Eradication and Gastric Cancer Prevention Trial (HELPER, NCT02112214), is currently ongoing in Korea in collaboration with the International Agency for Research on Cancer (IARC/WHO). The primary outcome of the trial is the incidence of gastric cancer in the treatment and the placebo groups.
Results 
The National Cancer Center Korea and 10 university hospitals in Korea participated in this study. The study had screened H. pylori status in > 12 000 average-risk Korean participants who had participated in the Korean National Cancer Screening Program (KNCSP) up to 2019. Individuals with H. pylori infection (> 5,200) were randomized to receive either bismuth quadruple therapy for H. pylori eradication or a placebo. The participants have been followed up with 2-year interval endoscopy through the KNCSP, and an interim analysis is planned after a 6-year follow-up period in 2026, if two-thirds of the expected target number of gastric cancers have developed by that time point.  A total of 36 gastric cancer cases were reported in the randomized group through active follow-up and data linkage with the National Cancer Registry Database by November 2025.   
Conclusions/Implications
Secondary prevention through the KNCSP, which offers biennial endoscopy to adults aged ≥40 years, has achieved high participation rates and is strongly associated with reduced gastric cancer mortality, stage migration to early disease, and increased use of endoscopic treatment. However, the current uniform screening strategy does not incorporate individual risk stratification and is costly. The HELPER study will provide high-quality evidence on the strategy of H. pylori eradication to prevent gastric cancer in the average-risk population in the Republic of Korea. Future integration of H. pylori eradication and objective assessment of gastric atrophy into risk-adapted screening and surveillance strategies may optimize effectiveness, reduce healthcare costs, and further decrease the burden of gastric cancer in Korea.