Helicobacter pylori eradication for primary prevention of gastric cancer: progresses and challenges

Abstract

Gastric cancer remains a significant global health challenge, causing a substantial number of cancer-related deaths, particularly in China. While the exact causes of gastric cancer are still being investigated, Helicobacter pylori (H. pylori) infection has been identified as the primary risk factor, which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time. Since the 1990s, numerous efforts have focused on assessing the effectiveness of H. pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment. This body of work, including several community-based interventions and meta-analyses, has shown a reduction in both the incidence of and mortality from gastric cancer following H. pylori treatment, alongside a decreased risk of metachronous gastric cancer. In this review, we seek to consolidate current knowledge on the effects of H. pylori treatment on gastric cancer prevention, its systemic consequences, cost-effectiveness, and the influence of antibiotic resistance and host characteristics on treatment outcomes. We further discuss the potential for precision primary prevention of H. pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.

Keywords: Cost-effectiveness; Gastric cancer; Helicobacter pylori; Intervention trial; Precision prevention.

Fig. 1

Research trajectory and implications of H. pylori eradication for gastric cancer prevention. The timeline compiles evidence from randomized controlled trials (RCTs) and observational studies, confirming that H. pylori eradication diminishes both GC incidence and mortality, and lowers metachronous GC risk. RCTs comparing H. pylori eradication to placebo or no intervention for GC prevention are categorized by trial locations that were highlighted by the map. The related trial studies are annotated with the longest follow-up durations, as reported in the most recent research. The necessity for tailored treatment approaches in GC prevention has been highlighted, and studies with long-term follow-up affirm the ‘test-and-treat’ strategy's effectiveness and cost-benefit, especially in high-risk Asian populations. The MITS trial, with its community-based nature, long-term follow-up and unique large sample size, further explores the feasibility of the ‘test-and-treat’ strategy, offering opportunities to develop more nuanced, personalized intervention strategies. GC, gastric cancer; H. pylori, Helicobacter pylori; MITS, Mass Intervention Trial in Shandong; RCT, randomized controlled trial.

Fig. 2

Integrated overview of H. pylori eradication and gastric cancer prevention strategies. The figure summarizes the dynamic interactions between antibiotic resistance and host factors that influence the outcomes of H. pylori eradication in the context of gastric cancer prevention, underscoring the transition to risk & benefit-tailored prevention strategies. The interplay of evolving antibiotic resistance patterns and individual patient characteristics contributes to a spectrum of treatment consequences, from shifts in microbiota structure to metabolic alterations, along with other divergent post-treatment effects. DOB, delta over baseline; GC, gastric cancer; H. pylori, Helicobacter pylori; MALT, mucosa-associated lymphoid tissue; NGS, next-generation sequencing; PUD, peptic ulcer disease.