Beyond the stomach - the association between Helicobacter pylori and the spectrum of digestive cancers

Sep 23, 2026

Helicobacter pylori (H. pylori) is a Group 1 gastric carcinogen increasingly linked to extragastric digestive malignancies. This review synthesizes evidence for its role in liver, biliary, esophageal, colorectal, and pancreatic cancers, describing how spiral morphology, motility, and urease-driven acidic niche adaptation disrupt host homeostasis through multifactorial virulence mechanisms. It summarizes site-specific epidemiology, including differing risk patterns for HCC, BTC, esophageal cancer, colorectal cancer, and pancreatic cancer, and discusses translational implications for risk stratification and therapeutic innovation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Carcinogenic potential and global burden

Evidence for extragastric oncogenesis

Mechanisms and virulence-driven pathways

TYPE Review PUBLISHED 02 September 2025 DOI 10.3389/fcimb.2025.1633227 OPEN ACCESS EDITED BY Asghar Ali, Jamia Hamdard University, India REVIEWED BY Mohammad Tahir Siddiqui, Indian Institute of Technology Delhi, India Mohammad Abid, Jamia Millia Islamia, India *CORRESPONDENCE Qingping Wang [qingpinganesky@163.com](qingpinganesky@163.com)[ ](qingpinganesky@163.com)Dongsheng Chen [dongsheng.chen@simceredx.com](dongsheng.chen@simceredx.com) †These authors have contributed equally to this work and share ﬁrst authorship RECEIVED 22 May 2025 ACCEPTED 04 August 2025 PUBLISHED 02 September 2025 CITATION Xin H, Zhu C, Zhu C, Zhang X, Chen D and Wang Q (2025) Beyond the stomach: the association between Helicobacter pylori and the spectrum of digestive cancers. Front. Cell. Infect. Microbiol. 15:1633227 . doi: 10.3389/fcimb.2025.1633227 COPYRIGHT © 2025 Xin, Zhu, Zhu, Zhang, Chen and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Beyond the stomach: the association between Helicobacter pylori and the spectrum of digestive cancers He Xin1,2†, Chi Zhu 3,4†, Chan Zhu 3,4, Xing Zhang 3,4 , Dongsheng Chen 3,4* and Qingping Wang 5,6* 1 Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China, 2 Intervention Ward One, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China, 3The State Key Laboratory of Neurology and Oncology Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China, 4 Department of Medicine, Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China, 5Tianjin Second People’s Hospital, Tianjin, China, 6Tianjin Institute of Hepatology, Tianjin, China Helicobacter pylori (H. pylori) is a Group 1 gastric carcinogen increasingly implicated in extragastric digestive malignancies. This review synthesizes evidence on its role in liver, biliary, esophageal, colorectal, and pancreatic cancers. Based on its unique spiral morphology, ﬂagellar motility bundle, and urease activity-mediated acidic niche adaptation, H. pylori disrupts host cellular homeostasis through multifactorial virulence mechanisms involving CagA/VacA synergy, and exploits antigenic variation and immunomodulatory strategies to achieve persistent gastric mucosal colonization and chronic infection. Emerging evidence suggests associations between H. pylori infection and nongastric digestive cancers, though relationships vary by site. For hepatocellular carcinoma (HCC), epidemiological studies indicate increased risk (OR 4.75), particularly with HCV coinfection, but mechanistic and cohort data remain conﬂicting. Biliary tract cancer (BTC) shows stronger epidemiological links, especially for cholangiocarcinoma (OR 4.18), supported by virulence factor detection. In esophageal cancer, H. pylori particularly CagA+ strains demonstrates a protective effect against adenocarcinoma but no signiﬁcant association with squamous cell carcinoma. Colorectal cancer exhibits complex associations, with meta-analyses suggesting increased risk in East Asian populations and potential beneﬁts from eradication therapy. Pancreatic cancer links remain inconsistent. Proposed mechanisms of H. pylori in extragastric cancers include chronic inﬂammation, virulence factor activity and microbiome disruption. This comprehensive review synthesizes contemporary evidence on the bacterium’s role in non-gastric digestive malignancies, examines pathways underlying its oncogenicity, and outlines translational implications for risk stratiﬁcation and therapeutic innovation. K

FAQs

What cancers does H. pylori associate with outside the stomach?

The review covers extragastric digestive cancers including liver (hepatocellular carcinoma), biliary tract (cholangiocarcinoma), esophageal cancer, colorectal cancer, and pancreatic malignancies.

How might H. pylori promote oncogenesis according to the review?

It proposes multifactorial virulence mechanisms, including CagA/VacA synergy, antigenic variation, immunomodulatory strategies, chronic inflammation, and disruption of the microbiome.

Are the epidemiological associations consistent across cancer types?

No. The review reports differing patterns by site, including stronger epidemiological links for biliary tract cancer, variable effects in esophageal cancer by strain type, complex colorectal associations, and inconsistent pancreatic cancer links.

Sep 23, 2026

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