Introduction
Gastric Cancer remains the fifth leading cause of cancer-related deaths worldwide, with nearly one million new cases diagnosed annually. Helicobacter pylori (H. pylori) infection is a well-established primary carcinogen for gastric cancer. Chronic colonization of H. pylori leads to persistent inflammation, gastric mucosal atrophy, and intestinal metaplasia, ultimately facilitating cancer development. While multiple randomized controlled trials (RCTs) suggest that eradicating H. pylori decreases gastric cancer risk, limitations such as small event numbers and short follow-up durations have resulted in inconsistent clinical guidelines regarding universal screening and eradication strategies. Moreover, no country has yet implemented a nationwide program targeting universal H. pylori screening and treatment, although regional pilot projects have shown promising outcomes. With the emergence of new large-scale RCTs and observational studies, there is an urgent need to synthesize evidence to clarify the true impact and public health value of eradication therapy.
Study Overview
Recently, researchers published a systematic review and meta-analysis titled “Eradication Therapy to Prevent Gastric Cancer in Helicobacter pylori–Positive Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies.” This analysis incorporated 11 RCTs and 13 high-quality observational cohort studies, encompassing over 150,000 H. pylori-infected individuals. The goal was to evaluate how eradication therapy influences the risk of developing gastric cancer and associated mortality.
Methods
Researchers comprehensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through October 2024. Included studies were RCTs comparing at least 7-day H. pylori eradication regimens versus placebo or no treatment, and observational cohorts comparing eradicated and non-eradicated groups. Relative risks (RR) were calculated using random-effects models, and the number needed to treat (NNT) was estimated to quantify clinical impact. Study quality and bias risks were rigorously assessed.
Key Findings
1. Results from RCTs in Healthy H. pylori-Positive Adults
Eight RCTs including 58,628 participants showed that eradication therapy reduced gastric cancer incidence from 1.2% in controls to 0.87% in treated individuals (RR=0.64; 95% CI 0.48–0.84; I²=35%). Trials with low bias risk yielded consistent results. Gastric cancer-related mortality decreased by 22% (RR=0.78; 95% CI 0.62–0.98). No significant difference was found in overall mortality (RR=0.98; 95% CI 0.87–1.11), supporting the safety of eradication therapy.
2. RCTs in Patients Undergoing Endoscopic Mucosal Resection (EMR)
Three RCTs involving 1,841 patients with early gastric cancer or severe atrophic gastritis demonstrated nearly a 50% reduction in future gastric cancer occurrence in the eradication group (RR=0.52; 95% CI 0.38–0.71), with an NNT of 18. These studies were conducted in East Asian countries with good endoscopic screening coverage and showed no heterogeneity.
3. Observational Study Evidence
Eleven cohort studies with 89,774 H. pylori-positive individuals without gastric cancer showed a 44% risk reduction in gastric cancer incidence following eradication (RR=0.56; 95% CI 0.43–0.73) with low heterogeneity. Two observational studies involving 269 post-EMR patients demonstrated a pronounced risk reduction in gastric cancer incidence after eradication (RR=0.19; 95% CI 0.06–0.61). Pooled observational data indicate an overall 47% reduction in gastric cancer risk with eradication therapy (RR=0.53; 95% CI 0.41–0.68).
4. Overall RCT Summary
Eleven RCTs totaling nearly 60,000 infected individuals confirmed that eradication therapy decreases gastric cancer risk by approximately 39% (RR=0.61; 95% CI 0.49–0.75).
Interpretation and Clinical Implications
This large-scale integration of RCT and high-quality observational data provides robust evidence that eradicating H. pylori infection substantially lowers both gastric cancer incidence and gastric cancer-related mortality, affirming its clinical preventive value. The inclusion of over 150,000 infected individuals greatly enhances statistical power and result reliability, overcoming limitations of previous smaller studies.
Notably, eradication therapy also significantly reduced subsequent gastric cancer risk in patients with existing gastric mucosal lesions requiring endoscopic treatment, challenging the previously held notion of an irreversible carcinogenic stage and supporting early intervention strategies.
Though observational studies inherently carry some bias risk, their findings align closely with RCT results, reinforcing the rationale for broader eradication efforts.
Limitations and Future Directions
Most data derive from East Asian populations, where gastric cancer rates are highest, limiting the generalizability to other regions. Future research should expand to diverse geographic populations to validate these findings globally.
The NNT analysis highlights particularly high public health benefits when targeting high-risk groups for H. pylori screening and eradication, suggesting focused interventions could substantially reduce gastric cancer burden.
Given the projected global increase in gastric cancer incidence and mortality, these findings provide strong evidence-based support for policymakers to incorporate H. pylori screening and eradication into national gastric cancer prevention strategies.
Conclusion
Eradication of Helicobacter pylori infection is a safe and effective strategy to significantly reduce gastric cancer risk and related mortality, especially among high-risk individuals and those with precancerous gastric lesions. This evidence advocates for the integration of systematic H. pylori screening and treatment programs into public health policies worldwide, aiming to curb the growing burden of gastric cancer.
References
Ford AC, Yuan Y, Park JY, Forman D, Moayyedi P. Eradication Therapy to Prevent Gastric Cancer in Helicobacter pylori–Positive Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies. Gastroenterology. 2025;169(2):261-276. doi:10.1053/j.gastro.2024.12.033
