Prevalence and co-detection of Helicobacter pylori, Epstein–Barr virus, and human papillomavirus in gastric tissues: a cross-sectional study from Yazd, Iran (2019–2022)
,
Abstract
Background and Objectives: Gastric cancer remains a leading cause of cancer mortality and exhibits significant geographic variation. Although Helicobacter pylori (H. pylori) is a well-established carcinogen, the contributions of Epstein–Barr virus (EBV) and human papillomavirus (HPV), individually or in conjunction with H. pylori, are not fully understood. This study assessed the prevalence and co-detection of these pathogens in gastric tissues from Yazd, Iran.
Materials and Methods: An archive-based cross-sectional study was conducted using 130 formalin-fixed, paraffin-embedded (FFPE) gastric specimens collected between 2019 and 2022, comprising 83 gastric adenocarcinomas and 47 non-malignant tissues. H. pylori was detected by conventional PCR targeting 16S rRNA, while EBV and HPV were identified by nested PCR targeting EBNA-1 and L1, respectively. PCR products were confirmed by agarose gel electrophoresis, and selected amplicons were verified by Sanger sequencing.
Results: H. pylori was detected in 74 of 130 specimens (56.9%), with a prevalence of 62.7% in malignant tissues and 46.8% in non-malignant tissues (p=0.080). EBV was identified in three malignant cases (3.6%) and HPV in one malignant case (1.2%), with no positive findings in non-malignant samples (p=0.187 and p=0.450, respectively). Three co-detections were observed in malignant tissues, including two cases of H. pylori with EBV and one case of H. pylori with HPV. Due to the limited number of EBV- and HPV-positive cases, association analyses lacked statistical power.
Conclusion: H. pylori was the predominant microorganism detected, while EBV and HPV were rare and co-detections were infrequent. Larger prospective studies employing complementary molecular techniques and H. pylori virulence profiling are required to elucidate the clinical significance of these infections in gastric carcinogenesis.
2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424.
3. Pourhoseingholi MA, Fazeli Z, Ashtari S, Bavand-Pour FS. Mortality trends of gastrointestinal cancers in Iranian population. Gastroenterol Hepatol Bed Bench 2013; 6(Suppl 1): S52-S57.
4. Liu Z, Xu H, You W, Pan K, Li W. Helicobacter pylori eradication for primary prevention of gastric cancer: progresses and challenges. J Natl Cancer Cent 2024; 4: 299-310.
5. Liou JM, Malfertheiner P, Smith SI, El-Omar EM, Wu MS. 40 years after the discovery of Helicobacter pylori: towards elimination of H pylori for gastric cancer prevention. Lancet 2024; 403: 2570-2572.
6. Alexander GA, Brawley OW. Association of Helicobacter pylori infection with gastric cancer. Mil Med 2000; 165: 21-27.
7. Sun K, Jia K, Lv H, Wang SQ, Wu Y, Lei H, et al. EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives. Front Oncol 2020; 10: 583463.
8. Zeng ZM, Luo FF, Zou LX, He RQ, Pan DH, Chen X, et al. Human papillomavirus as a potential risk factor for gastric cancer: a meta-analysis of 1,917 cases. Onco Targets Ther 2016; 9: 7105-7114.
9. Mazurek M, Jaros M, Gliwa AM, Sitarz MZ, Dudzińska E, Zinkiewicz K, et al. Epstein-Barr Virus (EBV) and Human Papilloma Virus (HPV) in Gastric Cancers, with Special Reference to Gastric Cancer at a Young Age-A Pilot Study in Poland. Int J Mol Sci 2025; 26: 711.
10. de Souza CRT, Almeida MCA, Khayat AS, da Silva EL, Soares PC, Chaves LC, et al. Association between Helicobacter pylori, Epstein-Barr virus, human papillomavirus and gastric adenocarcinomas. World J Gastroenterol 2018; 24: 4928-4938.
11. Charostad J, Azaran A, Nakhaei M, Astani A, Kaydani GA, Motamedfar A, et al. Upregulation of interleukin-6 in HPV-positive breast cancer patients. Iran J Immunol 2021; 18: 315-330.
12. Charostad J, Nakhaei M, Azaran A, Kaydani GA, Astani A, Motamedfar A, et al. MiRNA-218 is frequently downregulated in malignant breast tumors: a footprint of Epstein-Barr virus infection. Iran J Pathol 2021; 16: 376-385.
13. Kumar S, Metz DC, Ellenberg S, Kaplan DE, Goldberg DS. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology 2020; 158(3): 527-536.e7.
14. Bae JM. Human papillomavirus infection and gastric cancer risk: A meta-epidemiological review. World J Virol 2021; 10: 209-216.
15. Saito M, Kono K. Landscape of EBV-positive gastric cancer. Gastric Cancer 2021; 24: 983-989.
16. Shechter O, Sausen DG, Gallo ES, Dahari H, Borenstein R. Epstein-Barr Virus (EBV) Epithelial Associated Malignancies: Exploring Pathologies and Current Treatments. Int J Mol Sci 2022; 23: 14389.
17. Cândido AC, de Lima Filho JL, Martins DB, Mendes CM, Vieira JR, Ferraz AA. Association of human papillomavirus genomic sequences by polymerase chain reaction in gastric carcinomas in Brazil. Anal Quant Cytopathol Histpathol 2013; 35: 1-6.
18. Fakhraei F, Haghshenas MR, Hosseini V, Rafiei A, Naghshvar F, Alizadeh-Navaei R. Detection of human papillomavirus DNA in gastric carcinoma specimens in a high-risk region of Iran. Biomed Rep 2016; 5: 371-375.
19. Jafari-Sales A, Shariat A, Bannazadeh-Baghi H, Baradaran B, Jafari B. Human Papillomavirus (HPV) Prevalence and E6 Protein Expression in Gastric Cancer Tissue Samples Compared with Non-malignant and Control Groups in East Azerbaijan Province, Iran, 2021. Iran J Med Microbiol 2023; 17: 58-65.
20. Cárdenas-Mondragón MG, Torres J, Flores-Luna L, Camorlinga-Ponce M, Carreón-Talavera R, Gomez-Delgado A, et al. Case–control study of Epstein–Barr virus and Helicobacter pylori serology in Latin American patients with gastric disease. Br J Cancer 2015; 112: 1866-1873.
21. Singh S, Jha HC. Status of Epstein-Barr Virus Coinfection with Helicobacter pylori in Gastric Cancer. J Oncol 2017; 2017: 3456264.
22. Fierti AO, Yakass MB, Okertchiri EA, Adadey SM, Quaye O. The Role of Epstein-Barr Virus in Modulating Key Tumor Suppressor Genes in Associated Malignancies: Epigenetics, Transcriptional, and Post-Translational Modifications. Biomolecules 2022; 12: 127.
| Files | ||
| Issue | Vol 18 No 5 (2026) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v18i5.22867 | |
| Keywords | ||
| Helicobacter pylori Papillomavirus infections Epstein-Barr virus infections Coinfection | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
