Universitas Muhammadiyah Sidoarjo
Login


Indonesian Journal on Health Science and Medicine

 Submit manuscript
Section Articles

Helicobacter pylori: the Progression of Gastritis to Stomach Cancer

Vol. 2 No. 3 (2025): Desember:
DOI : https://doi.org/10.21070/ijhsm.v2i3.297
Published : Oct 24, 2025

Namaat R. Abdulla (1), Zainab W. Khudair (2), Al-Amery T.S (3), Noor R. Abdulla (4)

(1) Department of Forensic Science, Al-Nasiriyah Technical Institute, Southern Technical University, ThiQar Province, Iraq
(2) Department of Pathology and Poultry Diseases, Basrah University, Basrah, Iraq
(3) Ministry of Agriculture, Directorate of Agricultural Extension and Training, Basrah, Iraq
(4) Ministry of Agriculture, Veterinary Department, Dhi Qar, Iraq
Fulltext View | Download

Abstract:

General Background: Gastric cancer remains one of the most prevalent malignancies worldwide, with nearly one million new cases and over 700,000 deaths annually, largely linked to Helicobacter pylori infection. This gram-negative bacterium colonizes the gastric mucosa, causing chronic gastritis that can progress to malignancy. Specific Background: H. pylori is recognized as a Class I carcinogen by the International Agency for Research on Cancer due to its strong association with gastric adenocarcinoma. The infection triggers inflammatory and genetic responses that facilitate carcinogenesis through bacterial, host, and environmental interactions. Knowledge Gap: Despite decades of research, the molecular mechanisms linking H. pylori virulence factors to gastric epithelial transformation and the synergistic role of host and environmental cofactors remain insufficiently elucidated. Aims: This study reviews how H. pylori infection progresses from gastritis to gastric cancer by detailing bacterial virulence determinants, host inflammatory responses, and environmental contributors. Results: Key virulence factors such as CagA, VacA, BabA, and OipA disrupt epithelial integrity, modulate signaling pathways (e.g., NF-κB, Wnt/β-catenin), and trigger cytokine overexpression, fostering neoplastic changes. Novelty: The review integrates molecular, immunologic, and environmental dimensions of H. pylori pathogenesis, highlighting their collective role in carcinogenic transformation. Implications: Understanding these multifactorial mechanisms underscores the need for early detection, eradication therapies, and targeted prevention strategies to reduce gastric cancer mortality.
Highlight :




  • H. pylori infection can progress from gastritis to gastric cancer through chronic inflammation and mucosal damage.




  • The bacterium’s virulence factors and host immune response play crucial roles in disease progression.




  • Early detection and eradication of H. pylori are vital to prevent gastric cancer development.




Keywords : Helicobacter Pylori, Gastritis, Gastric Cancer, Virulence Factors, Cytokines

References

A. Ferro, B. Peleteiro, M. Malvezzi, C. Bosetti, P. Bertuccio, F. Levi, E. Negri, C. La Vecchia, and N. Lunet, “Worldwide Trends in Gastric Cancer Mortality (1980–2011), with Predictions to 2015, and Incidence by Subtype,” Eur. J. Cancer, vol. 50, pp. 1330–1344, 2014.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward, and D. Forman, “Global Cancer Statistics,” CA Cancer J. Clin., vol. 61, pp. 69–90, 2011.

P. Correa, “Human Gastric Carcinogenesis: A Multistep and Multifactorial Process—First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention,” Cancer Res., vol. 52, pp. 6735–6740, 1992.

V. Herrera and J. Parsonnet, “Helicobacter Pylori and Gastric Adenocarcinoma,” Clin. Microbiol. Infect., vol. 15, pp. 971–976, 2009.

P. Malfertheiner, F. Megraud, C. A. O’Morain, et al., “Management of Helicobacter Pylori Infection—The Maastricht IV/Florence Consensus Report,” Gut, vol. 61, no. 5, pp. 646–664, 2012.

D. B. Polk and R. M. Peek, “Helicobacter Pylori: Gastric Cancer and Beyond,” Nat. Rev. Cancer, vol. 10, no. 6, pp. 403–414, 2010.

S. Kayali, M. Manfredi, F. Gaiani, L. Bianchi, B. Bizzarri, G. Leandro, F. Di Mario, and G. L. De’ Angelis, “Helicobacter Pylori, Transmission Routes and Recurrence of Infection: State of the Art,” Acta Biomed., vol. 89, no. 8-S, pp. 72–76, 2018, doi: 10.23750/abm.v89i8-S.7947.

K. M. Salih, O. A. Elfaki, Y. H. Hamid, W. M. Eldouch, M. Diab, and S. O. Abdelgadir, “Prevalence of Helicobacter Pylori Among Sudanese Children Admitted to a Specialised Children Hospital,” Sudanese J. Paediatrics, vol. 17, no. 1, p. 14, 2017.

J. G. Kusters, A. H. van Vliet, and E. J. Kuipers, “Pathogenesis of Helicobacter Pylori Infection,” Clin. Microbiol. Rev., vol. 19, no. 3, pp. 449–490, 2006.

O. M. Etukudo, E. E. Ikpeme, and E. E. Ekanem, “Seroepidemiology of Helicobacter Pylori Infection Among Children Seen in a Tertiary Hospital in Uyo, Southern Nigeria,” Pan Afr. Med. J., vol. 12, no. 1, 2012.

G. Bizzozero, “Ueber die Schlauchförmigen Drüsen des Magendarmkanals und die Beziehungen Ihres Epithels zu dem Oberflächenepithel der Schleimhaut Dritte Mittheilung,” Arch. Für Mikrosk. Anat., vol. 42, pp. 82–152, 1893.

B. J. Marshall and J. R. Warren, “Unidentified Curved Bacilli in the Stomach of Patients with Gastritis and Peptic Ulceration,” Lancet, vol. 1, pp. 1311–1315, 1984.

D. M. Parkin, F. Bray, J. Ferlay, and P. Pisani, “Global Cancer Statistics, 2002,” CA Cancer J. Clin., vol. 55, pp. 74–108, 2005.

P. Correa, “Is Gastric Cancer Preventable?,” Gut, vol. 53, pp. 1217–1219, 2004.

P. Correa, “Human Gastric Carcinogenesis: A Multistep and Multifactorial Process—First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention,” Cancer Res., vol. 52, pp. 6735–6740, 1992.

P. Correa, “Helicobacter Pylori and Gastric Cancer: State of the Art,” Cancer Epidemiol. Biomarkers Prev., vol. 5, pp. 477–481, 1996.

P. Correa and J. Houghton, “Carcinogenesis of Helicobacter Pylori,” Gastroenterology, vol. 133, pp. 659–672, 2007.

M. Hatakeyama, “Oncogenic Mechanisms of the Helicobacter Pylori CagA Protein,” Nat. Rev. Cancer, vol. 4, pp. 688–694, 2004.

J. C. Atherton, “The Pathogenesis of Helicobacter Pylori-Induced Gastro-Duodenal Diseases,” Annu. Rev. Pathol., vol. 1, pp. 63–96, 2006.

N. Uemura, S. Okamoto, S. Yamamoto, N. Matsumura, S. Yamaguchi, M. Yamakido, K. Taniyama, N. Sasaki, and R. J. Schlemper, “Helicobacter Pylori Infection and the Development of Gastric Cancer,” N. Engl. J. Med., vol. 345, pp. 784–789, 2001.

M.-S. Wu, C.-J. Chen, and J.-T. Lin, “Host-Environment Interactions: Their Impact on Progression from Gastric Inflammation to Carcinogenesis and on Development of New Approaches to Prevent and Treat Gastric Cancer,” Cancer Epidemiol. Biomarkers Prev., vol. 14, pp. 1878–1882, 2005.

M. C. Tan, M. Balakrishnan, and D. Y. Graham, “Gastric Cancer Worldwide Except Japan,” in Gastric Cancer with Special Focus on Studies from Japan, A. Shiotani, Ed. Singapore: Springer, 2018, pp. 17–28.

A. C. Ford, D. Forman, R. H. Hunt, et al., “Helicobacter Pylori Eradication Therapy to Prevent Gastric Cancer in Healthy Asymptomatic Infected Individuals: Systematic Review and Meta-Analysis of Randomised Controlled Trials,” BMJ, vol. 348, g3174, 2014.

Y. C. Lee, T. H. Chiang, C. K. Chou, et al., “Association Between Helicobacter Pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-Analysis,” Gastroenterology, vol. 150, pp. 1113–1124, 2016.

A. C. Ford, Y. Yuan, and P. Moayyedi, “Helicobacter Pylori Eradication Therapy to Prevent Gastric Cancer: Systematic Review and Meta-Analysis,” Gut, vol. 69, pp. 2113–2121, 2020.

H. B. El-Serag, J. Y. Kao, F. Kanwal, et al., “Houston Consensus Conference on Testing for Helicobacter Pylori Infection in the United States,” Clin. Gastroenterol. Hepatol., vol. 16, pp. 992–1002, 2018.

L. E. Wroblewski, R. M. Peek, and K. T. Wilson, “Helicobacter Pylori and Gastric Cancer: Factors That Modulate Disease Risk,” Clin. Microbiol. Rev., vol. 23, no. 4, pp. 713–739, 2010, doi: 10.1128/cmr.00011-10.

N. Tegtmeyer, S. Wessler, and S. Backert, “Role of the Cag-Pathogenicity Island Encoded Type IV Secretion System in Helicobacter Pylori Pathogenesis,” FEBS J., vol. 278, pp. 1190–1202, 2011, doi: 10.1111/j.1742-4658.2011.08035.x.

A. Takahashi-Kanemitsu, C. T. Knight, and M. Hatakeyama, “Molecular Anatomy and Pathogenic Actions of Helicobacter Pylori CagA That Underpin Gastric Carcinogenesis,” Cell Mol. Immunol., vol. 17, pp. 50–63, 2020, doi: 10.1038/s41423-019-0339-5.

H. Higashi, R. Tsutsumi, S. Muto, T. Sugiyama, T. Azuma, M. Asaka, and M. Hatakeyama, “SHP-2 Tyrosine Phosphatase as an Intracellular Target of Helicobacter Pylori CagA Protein,” Science, vol. 295, pp. 683–686, 2002, doi: 10.1126/science.1067147.

R. Tsutsumi, A. Takahashi, T. Azuma, H. Higashi, and M. Hatakeyama, “Focal Adhesion Kinase is a Substrate and Downstream Effector of SHP-2 Complexed with Helicobacter Pylori CagA,” Mol. Cell Biol., vol. 26, pp. 261–276, 2006, doi: 10.1128/MCB.26.1.261-276.2006.

M. Selbach, S. Moese, R. Hurwitz, C. R. Hauck, T. F. Meyer, and S. Backert, “The Helicobacter Pylori CagA Protein Induces Cortactin Dephosphorylation and Actin Rearrangement by c-Src Inactivation,” EMBO J., vol. 22, pp. 515–528, 2003, doi: 10.1093/emboj/cdg050.

I. Saadat, H. Higashi, C. Obuse, et al., “Helicobacter Pylori CagA Targets PAR1/MARK Kinase to Disrupt Epithelial Cell Polarity,” Nature, vol. 447, pp. 330–333, 2007, doi: 10.1038/nature05765.

S. S. Kim, V. E. Ruiz, J. D. Carroll, and S. F. Moss, “Helicobacter Pylori in the Pathogenesis of Gastric Cancer and Gastric Lymphoma,” Cancer Lett., vol. 305, pp. 228–238, 2011, doi: 10.1016/j.canlet.2010.07.014.

S. Alzahrani, T. T. Lina, J. Gonzalez, I. V. Pinchuk, E. J. Beswick, and V. E. Reyes, “Effect of Helicobacter Pylori on Gastric Epithelial Cells,” World J. Gastroenterol., vol. 20, pp. 12767–12780, 2014, doi: 10.3748/wjg.v20.i36.12767.

S. L. Palframan, T. Kwok, and K. Gabriel, “Vacuolating Cytotoxin A (VacA), a Key Toxin for Helicobacter Pylori Pathogenesis,” Front. Cell Infect. Microbiol., vol. 2, p. 92, 2012, doi: 10.3389/fcimb.2012.00092.

M. S. Sundrud, V. J. Torres, D. Unutmaz, and T. L. Cover, “Inhibition of Primary Human T Cell Proliferation by Helicobacter Pylori Vacuolating Toxin (VacA) is Independent of VacA Effects on IL-2 Secretion,” Proc. Natl. Acad. Sci. U.S.A., vol. 101, pp. 7727–7732, 2004, doi: 10.1073/pnas.0401528101.

B. Hoy, M. Löwer, C. Weydig, et al., “Helicobacter Pylori HtrA is a New Secreted Virulence Factor that Cleaves E-Cadherin to Disrupt Intercellular Adhesion,” EMBO Rep., vol. 11, pp. 798–804, 2010, doi: 10.1038/embor.2010.114.

G. Posselt, J. E. Crabtree, and S. Wessler, “Proteolysis in Helicobacter Pylori-Induced Gastric Cancer,” Toxins (Basel), vol. 9, p. 134, 2017, doi: 10.3390/toxins9040134.

W. L. Chang, Y. C. Yeh, and B. S. Sheu, “The Impacts of H. Pylori Virulence Factors on the Development of Gastroduodenal Diseases,” J. Biomed. Sci., vol. 25, p. 68, 2018, doi: 10.1186/s12929-018-0466-9.

B. M. Roesler, E. M. Rabelo-Gonçalves, and J. M. Zeitune, “Virulence Factors of Helicobacter Pylori: A Review,” Clin. Med. Insights Gastroenterol., vol. 7, p. 9, 2014, doi: 10.4137/CGast.S13760.

M. E. Kable, L. M. Hansen, C. M. Styer, et al., “Host Determinants of Expression of the Helicobacter Pylori BabA Adhesin,” Sci. Rep., vol. 7, p. 46499, 2017, doi: 10.1038/srep46499.

Y. Yamaoka, “Increasing Evidence of the Role of Helicobacter Pylori SabA in the Pathogenesis of Gastroduodenal Disease,” J. Infect. Dev. Ctries., vol. 2, pp. 174–181, 2008, doi: 10.3855/jidc.259.

M. Unemo, M. Aspholm-Hurtig, D. Ilver, J. Bergström, T. Borén, D. Danielsson, and S. Teneberg, “The Sialic Acid Binding SabA Adhesin of Helicobacter Pylori is Essential for Nonopsonic Activation of Human Neutrophils,” J. Biol. Chem., vol. 280, pp. 15390–15397, 2005, doi: 10.1074/jbc.M412725200.

V. Ricci, M. Giannouli, M. Romano, and R. Zarrilli, “Helicobacter Pylori Gamma-Glutamyl Transpeptidase and Its Pathogenic Role,” World J. Gastroenterol., vol. 20, pp. 630–638, 2014, doi: 10.3748/wjg.v20.i3.630.

M. Gong, S. S. Ling, S. Y. Lui, K. G. Yeoh, and B. Ho, “Helicobacter Pylori Gamma-Glutamyl Transpeptidase is a Pathogenic Factor in the Development of Peptic Ulcer Disease,” Gastroenterology, vol. 139, pp. 564–573, 2010, doi: 10.1053/j.gastro.2010.03.050.

J. Zhang, J. Qian, X. Zhang, and Q. Zou, “Outer Membrane Inflammatory Protein A, a New Virulence Factor Involved in the Pathogenesis of Helicobacter Pylori,” Mol. Biol. Rep., vol. 41, pp. 7807–7814, 2014, doi: 10.1007/s11033-014-3673-9.

J. Baj, A. Forma, M. Sitarz, P. Portincasa, G. Garruti, D. Krasowska, and R. Maciejewski, “Helicobacter Pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment,” Cells, vol. 10, p. 27, 2020, doi: 10.3390/cells10010027.

O. Teymournejad, A. M. Mobarez, Z. M. Hassan, and A. Talebi Bezmin Abadi, “Binding of the Helicobacter Pylori OipA Causes Apoptosis of Host Cells via Modulation of Bax/Bcl-2 Levels,” Sci. Rep., vol. 7, p. 8036, 2017, doi: 10.1038/s41598-017-08176-7.

O. Teymournejad, A. M. Mobarez, Z. M. Hassan, S. M. Moazzeni, and H. N. Ahmadabad, “In Vitro Suppression of Dendritic Cells by Helicobacter Pylori OipA,” Helicobacter, vol. 19, pp. 136–143, 2014, doi: 10.1111/hel.12107.

E. M. El-Omar, C. S. Rabkin, M. D. Gammon, et al., “Increased Risk of Noncardia Gastric Cancer Associated with Proinflammatory Cytokine Gene Polymorphisms,” Gastroenterology, vol. 124, pp. 1193–1201, 2003, doi: 10.1016/s0016-5085(03)00157-4.

H. Kirikoshi, H. Sekihara, and M. Katoh, “Up-Regulation

of Wnt10A by Tumor Necrosis Factor α and Helicobacter Pylori in Gastric Cancer,” Int. J. Oncol., vol. 19, pp. 533–536, 2001, doi: 10.3892/ijo.19.3.533.

B. T. MacDonald, K. Tamai, and X. He, “Wnt/Beta-Catenin Signaling: Components, Mechanisms, and Diseases,” Dev. Cell, vol. 17, pp. 9–26, 2009, doi: 10.1016/j.devcel.2009.06.016.

K. Oguma, H. Oshima, M. Aoki, et al., “Activated Macrophages Promote Wnt Signalling Through Tumour Necrosis Factor-Alpha in Gastric Tumour Cells,” EMBO J., vol. 27, pp. 1671–1681, 2008, doi: 10.1038/emboj.2008.105.

E. M. El-Omar, M. Carrington, W. H. Chow, et al., “Interleukin-1 Polymorphisms Associated with Increased Risk of Gastric Cancer,” Nature, vol. 404, pp. 398–402, 2000, doi: 10.1038/35006081.

K. E. Lee, P. N. Khoi, Y. Xia, et al., “Helicobacter Pylori and Interleukin-8 in Gastric Cancer,” World J. Gastroenterol., vol. 19, pp. 8192–8202, 2013, doi: 10.3748/wjg.v19.i45.8192.

N. Sánchez-Zauco, J. Torres, A. Gómez, et al., “Circulating Blood Levels of IL-6, IFN-γ, and IL-10 as Potential Diagnostic Biomarkers in Gastric Cancer: A Controlled Study,” BMC Cancer, vol. 17, p. 384, 2017, doi: 10.1186/s12885-017-3310-9.

S. Maeda, M. Akanuma, Y. Mitsuno, et al., “Distinct Mechanism of Helicobacter Pylori-Mediated NF-Kappa B Activation Between Gastric Cancer Cells and Monocytic Cells,” J. Biol. Chem., vol. 276, pp. 44856–44864, 2001, doi: 10.1074/jbc.M105381200.

O. Sokolova and M. Naumann, “NF-κB Signaling in Gastric Cancer,” Toxins (Basel), vol. 9, p. 119, 2017, doi: 10.3390/toxins9040119.

J. Concetti and C. L. Wilson, “NFKB1 and Cancer: Friend or Foe?,” Cells, vol. 7, p. 133, 2018, doi: 10.3390/cells7090133.

N. Li, C. Xie, and N. H. Lu, “P53, a Potential Predictor of Helicobacter Pylori Infection-Associated Gastric Carcinogenesis?,” Oncotarget, vol. 7, pp. 66276–66278, 2016, doi: 10.18632/oncotarget.11414.

J. Wei, T. A. Nagy, A. Vilgelm, et al., “Regulation of P53 Tumor Suppressor by Helicobacter Pylori in Gastric Epithelial Cells,” Gastroenterology, vol. 139, pp. 1333–1343, 2010, doi: 10.1053/j.gastro.2010.06.018.

M. M. Rahman, M. A. Sarker, M. M. Hossain, et al., “Association of P53 Gene Mutation with Helicobacter Pylori Infection in Gastric Cancer Patients and Its Correlation with Clinicopathological and Environmental Factors,” World J. Oncol., vol. 10, p. 46, 2019, doi: 10.14740/wjon1087.

L. D. Butcher, G. den Hartog, P. B. Ernst, and S. E. Crowe, “Oxidative Stress Resulting from Helicobacter Pylori Infection Contributes to Gastric Carcinogenesis,” Cell Mol. Gastroenterol. Hepatol., vol. 3, pp. 316–322, 2017, doi: 10.1016/j.jcmgh.2017.02.002.

J. A. Gaddy, J. N. Radin, J. T. Loh, et al., “High Dietary Salt Intake Exacerbates Helicobacter Pylori-Induced Gastric Carcinogenesis,” Infect. Immun., vol. 81, pp. 2258–2267, 2013, doi: 10.1128/IAI.01271-12.

J. T. Loh, D. B. Friedman, M. B. Piazuelo, et al., “Analysis of Helicobacter Pylori CagA Promoter Elements Required for Salt-Induced Upregulation of CagA Expression,” Infect. Immun., vol. 80, pp. 3094–3106, 2012, doi: 10.1128/IAI.00232-12.

X. Q. Wang, H. Yan, P. D. Terry, J. S. Wang, W. A. Wu, and S. K. Hu, “Interactions Between CagA and Smoking in Gastric Cancer,” World J. Gastroenterol., vol. 17, pp. 3330–3334, 2011, doi: 10.3748/wjg.v17.i28.3330.

M. Santibáñez, E. Aguirre, S. Belda, et al., “Relationship Between Tobacco, CagA and VacA I1 Virulence Factors and Bacterial Load in Patients Infected by Helicobacter Pylori,” PLoS One, vol. 10, e0120444, 2015, doi: 10.1371/journal.pone.0120444.