Acid-Suppressive Therapy after Helicobacter Pylori Eradication and Subsequent Gastric Cancer Risk: A Systematic Review
DOI:
https://doi.org/10.37287/ijghr.v8i6.2823Keywords:
gastric neoplasms, helicobacter pylori, histamine h2 antagonists, proton pump inhibitors, risk factorsAbstract
Acid-suppressive therapy is frequently used after Helicobacter pylori (H. pylori) eradication, but its association with subsequent gastric cancer remains uncertain. This systematic review evaluated the relationship between post-eradication acid-suppressive therapy and gastric cancer risk, including associations according to treatment duration, frequency, and dose. This systematic review was conducted according to PRISMA 2020. PubMed/MEDLINE, Cochrane Library, Web of Science, and Scopus were searched from inception to September 25, 2026. Studies published between 2018 and 2026 were included if they evaluated adults who underwent Helicobacter pylori eradication and subsequently received acid-suppressive therapy, including proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), or histamine-2 receptor antagonists (H2RAs). The primary outcome was subsequent gastric cancer, including incident and metachronous cancer. Risk of bias was assessed using ROBINS-I V2. Findings were synthesized narratively. Seven retrospective cohort studies involving 571 to 288,182 participants were included. Five studies evaluated PPI exposure and two evaluated P-CABs. Four of five PPI studies reported statistically significant associations with gastric cancer, with effect estimates ranging from aHR 1.15 to 3.61, whereas one study comparing PPI with H2RA use found no significant association (aHR 1.30, 95% CI 0.75–2.27). Both P-CAB studies reported increased risk, including HR 1.92 (95% CI 1.13–3.25) for vonoprazan versus H2RA and aHR 3.89 (95% CI 2.45–5.74) for P-CAB versus non-use. Longer treatment duration, higher frequency, and greater dose or cumulative exposure were generally associated with higher risk estimates. Overall risk of bias was moderate in two studies and serious in five. Post-eradication PPI and P-CAB use was associated with increased gastric cancer risk in several observational cohorts, with higher risk estimates generally observed with more prolonged or intensive exposure.
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