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World J Gastroenterol. Nov 7, 2015; 21(41): 11654-11672
Published online Nov 7, 2015. doi: 10.3748/wjg.v21.i41.11654
Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions
Aleksandra Sokic-Milutinovic, Tamara Alempijevic, Tomica Milosavljevic
Aleksandra Sokic-Milutinovic, Tamara Alempijevic, Tomica Milosavljevic, Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia and School of Medicine University of Belgrade, 11000 Belgrade, Serbia
Author contributions: Sokic-Milutinovic A, Alempijevic T and Milosavljevic T did literature research and wrote the paper; and Sokic-Milutinovic A approved final version of the manuscript.
Conflict-of-interest statement: Authors have no conflict of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Aleksandra Sokic-Milutinovic, MD, PhD, Professor, Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia and School of Medicine University of Belgrade, Koste Todorovica 6, 11000 Belgrade, Serbia. asokicmilutinovic@gmail.com
Telephone: +381-11-3663734 Fax: +381-11-3615432
Received: May 21, 2015
Peer-review started: May 22, 2015
First decision: June 23, 2015
Revised: July 16, 2015
Accepted: September 22, 2015
Article in press: September 22, 2015
Published online: November 7, 2015
Processing time: 166 Days and 12.7 Hours
Abstract

Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available.

Keywords: Helicobacter pylori; Gastric cancer; Vaccine; Eradication therapy; Prevention

Core tip: Two main therapeutic strategies could reduce the incidence of Helicobacter pylori (H. pylori)-related gastric cancer: eradication of the infection or vaccination. Success of a gastric cancer prevention strategy depends on the eradication of the infection or on vaccination before irreversible mucosal changes (severe atrophy, intestinal metaplasia or dysplasia) have occurred. Eradication therapy results are suboptimal due to increased antibiotic resistance in H. pylori and patient noncompliance. To improve the rates of eradication, rescue regimens have been developed. Concomitant and sequential protocols seem equally effective rescue strategies. An effective vaccine is not available at present, in spite of enormous effort by different researchers.