Helicobacter pylori and Cancer: What’s the Link?

Elettra Merola,1 Giovanni Mario Pes,1 David Yates Graham,2,3 Maria Pina Dore1,2 1Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy; 2Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA; 3Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USACorrespondence: David Yates Graham, Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd (111D), Houston, TX, 77030, USA, Email [email protected]: Helicobacter pylori (H. pylori) is a human bacterial pathogen that causes one of the most common chronic bacterial infections worldwide. The microorganism has been classified by the International Agency for Research on Cancer as a Group I carcinogen. While the etiological link to gastric cancer is well established, the precise molecular and cellular mechanisms driving this transformation are highly complex and incompletely understood. Fundamentally, the infection results from the chronic presence of acute on chronic gastric mucosal inflammation. H. pylori pathogenicity is increased by bacterial virulence factors including the cytotoxin-associated gene A (CagA) and Vacuolating cytotoxin A (VacA) which may interfere with the host’s cell communication and create a pro-tumorigenic microenvironment. Host microRNAs (miRNAs) may amplify these effects by modulating immune responses, enhancing oncogenic signalling. Despite the proven benefits of H. pylori eradication in reducing cancer risk, especially in high-incidence regions, rising antibiotic resistance and host-related variables impede its global implementation. Recent advances in genomics and multi-omics profiling potentially offer new opportunities for targeted prevention. Moreover, emerging evidence suggests H. pylori may also negatively influence immunotherapy outcomes, underscoring its broader relevance in cancer treatment planning. By synthesizing molecular insights, epidemiological trends, and clinical data, this narrative review examines the multifaceted pathways through which H. pylori contributes to gastric carcinogenesis, integrating current knowledge on microbial virulence, host signalling disruption, immune modulation, and epigenetic remodelling.Keywords: Helicobacter pylori, gastric cancer, pathogenesis, CagA, VacA, virulence