Volume 17, Issue 2 (June-2025 2025)                   Iranian Journal of Blood and Cancer 2025, 17(2): 58-69 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Jafari-Sales A, Shiri Aghbash P, Sadeghi-Deylamdeh Z, Jahangirimehr F, Hosseini S M, Amini N, et al . A Comprehensive Study of Prostate Cancer and Epstein-Barr Virus Infection: A Systematic Review and Meta-analysis. Iranian Journal of Blood and Cancer 2025; 17 (2) :58-69
URL: http://ijbc.ir/article-1-1724-en.html
A Comprehensive Study of Prostate Cancer and Epstein-Barr Virus Infection: A Systematic Review and Meta-analysis
Abolfazl Jafari-Sales1 , Parisa Shiri Aghbash2 , Zahra Sadeghi-Deylamdeh3 , Fatemeh Jahangirimehr4 , Sayed Mohsen Hosseini4 , Nooshin Amini5 , Mehrdad Pashazadeh *6 , Hamidreza Fathi2 , Hossein Bannazadeh Baghi2
1- Department of Microbiology, Kaz.C., Islamic Azad University, Kazerun, Iran.
2- Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
3- Department of Biology, Faculty of Sciences, Malayer Branch, Malayer, Iran
4- Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran
5- Department of Medical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran.
6- Department of Medical Laboratory Sciences and Microbiology, Faculty of Medical Sciences, TaMS.C., Islamic Azad University, Tabriz, Iran. , mehrdadpashazadeh85@gmail.com
Abstract:   (783 Views)
This systematic review and meta-analysis examine the potential link between Epstein-Barr virus infection and prostate cancer development, highlighting its role in the second most common malignancy in developed countries. A complete literature search was conducted using PubMed, EMBASE, Scopus, and Web of Science to identify relevant studies published between 2002 and 2024. The study incorporated publications from various countries, peer-reviewed studies, systematic reviews, and meta-analyses as supplementary sources to identify additional relevant studies. The study analyzed data from 16 articles, involving 1,340 PC cases, assessing EBV detection based on geographical distribution, publication year, and EBV-positive cases. The odds ratio for EBV-associated PC was 26.79%, with a global prevalence of 0.38. The study indicates regional variations in EBV positivity among PC cases, suggesting a possible link between EBV infection and PC, but further research is needed to clarify its role.
Keywords: Epstein-Barr virus, Prevalence, Prostate cancer, Risk factor
Full-Text [PDF 953 kb]   (772 Downloads)    
: Meta-analysis | Subject: Infectious Diseases
Received: 2025/05/23 | Accepted: 2025/06/21 | Published: 2025/06/30
References
1. Pienta, K.J. and P.S. Esper, Risk factors for prostate cancer. Ann Intern Med, 1993. 118(10): p. 793-803. [DOI:10.7326/0003-4819-118-10-199305150-00007]
2. Bray, F., et al., Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024. 74(3): p. 229-263. [DOI:10.3322/caac.21834]
3. Baladehi, R.F., et al., The Effect of Oncogene Proteins of Human Papillomaviruses on Apoptosis Pathways in Prostate Cancer. Oncologie, 2022. 24(2): p. 227-245. [DOI:10.32604/oncologie.2022.020648]
4. Merriel, S.W., G. Funston, and W. Hamilton, Prostate cancer in primary care. Advances in therapy, 2018. 35(9): p. 1285-1294. [DOI:10.1007/s12325-018-0766-1]
5. King, A. and J. Broggio, Cancer registration statistics, England: 2016, 2018. Office of National Statistics: England.
6. Rosen, R., et al., Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol, 2003. 44(6): p. 637-49. [DOI:10.1016/j.eururo.2003.08.015]
7. Correas, J.M., et al., Advanced ultrasound in the diagnosis of prostate cancer. World J Urol, 2021. 39(3): p. 661-676. [DOI:10.1007/s00345-020-03193-0]
8. Cirulli, G.O., et al., Comparing PSA Screening Patterns and Their Role as Predictor of Prostate Cancer Diagnosis: Analysis of a Contemporary North American Cohort. Prostate, 2025: p. e24856. [DOI:10.1002/pros.24856]
9. Fazekas, T., et al., Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis. JAMA Oncol, 2024. 10(6): p. 745-754. [DOI:10.1001/jamaoncol.2024.0734]
10. Xiang, J., et al., Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis. World J Surg Oncol, 2019. 17(1): p. 31. [DOI:10.1186/s12957-019-1573-0]
11. Mallah, H., et al., Prostate Cancer: A Journey Through Its History and Recent Developments. Cancers (Basel), 2025. 17(2). [DOI:10.3390/cancers17020194]
12. Mandel, A., et al., Urology robotic prostate surgery, in Handbook of Robotic Surgery. 2025, Elsevier. p. 397-405. [DOI:10.1016/B978-0-443-13271-1.00051-0]
13. Ibrahim, I., et al., Impact of Centralisation of Radical Prostatectomy Driven by the Introduction of Robotic Systems on Positive Surgical Margin and Biochemical Recurrence in pT2 Prostate Cancer. Cancer Med, 2025. 14(2): p. e70514. [DOI:10.1002/cam4.70514]
14. Slevin, F., et al., A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer. Eur Urol Oncol, 2024. 7(4): p. 677-696. [DOI:10.1016/j.euo.2023.11.018]
15. Roy, S., et al., Helical Tomotherapy Versus 3-Dimensional Conformal Radiation Therapy in High-Risk Prostate Cancer: A Phase 3 Randomized Controlled Trial. Int J Radiat Oncol Biol Phys, 2024. 120(5): p. 1386-1393. [DOI:10.1016/j.ijrobp.2024.05.032]
16. Efstathiou, J.A., et al., Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Localized Prostate Cancer. International Journal of Radiation Oncology*Biology*Physics, 2024. 120(2). [DOI:10.1016/j.ijrobp.2024.08.012]
17. Sosa, A.J., et al., Proton therapy toxicity outcomes for localized prostate cancer: Long-term results at a comprehensive cancer center. Clin Transl Radiat Oncol, 2024. 48: p. 100822. [DOI:10.1016/j.ctro.2024.100822]
18. Board, P.A.T.E., Prostate Cáncer Treatment (PDQ®), in PDQ Cancer Information Summaries [Internet]. 2020, National Cancer Institute (US).
19. Desai, K., J.M. McManus, and N. Sharifi, Hormonal Therapy for Prostate Cancer. Endocr Rev, 2021. 42(3): p. 354-373. [DOI:10.1210/endrev/bnab002]
20. Preciado, M.V., et al., Presence of Epstein-Barr virus and strain type assignment in Argentine childhood Hodgkin's disease. Blood, 1995. 86(10): p. 3922-9. [DOI:10.1182/blood.V86.10.3922.bloodjournal86103922]
21. Jafari-Sales, A., et al., The presence of human papillomavirus and Epstein-Barr virus infection in gastric cancer: a systematic study. Oncologie, 2022. 24(3): p. 413-426. [DOI:10.32604/oncologie.2022.024161]
22. Ebrahimi, F., et al., Coinfection of EBV with other pathogens: a narrative review. Frontiers in Virology, 2024. 4: p. 1482329. [DOI:10.3389/fviro.2024.1482329]
23. Takada, K., Epstein-Barr virus and gastric carcinoma. Mol Pathol, 2000. 53(5): p. 255-61. [DOI:10.1136/mp.53.5.255]
24. Ebadi, A., et al., The frequency of Epstein-Barr virus EBNA-1 and BARF-1 genes in gastric adenocarcinoma patients. Health Biotechnology and Biopharma (HBB), 2024. 8(2): p. 1-15.
25. Ebadi, A., et al., Investigating the role of microRNAs, inflammation, and Helicobacter pylori in Epstein-Barr virus associated gastric cancer. Journal of Experimental and Clinical Medicine, 2023. 40(3): p. 646-658.
26. Wong, M.P., et al., In situ detection of Epstein-Barr virus in non-small cell lung carcinomas. J Pathol, 1995. 177(3): p. 233-40. [DOI:10.1002/path.1711770304]
27. Fina, F., et al., Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas. Br J Cancer, 2001. 84(6): p. 783-90. [DOI:10.1054/bjoc.2000.1672]
28. Bergh, J., et al., No link between viral findings in the prostate and subsequent cancer development. British journal of cancer, 2007. 96(1): p. 137-139. [DOI:10.1038/sj.bjc.6603480]
29. Sfanos, K.S., et al., A molecular analysis of prokaryotic and viral DNA sequences in prostate tissue from patients with prostate cancer indicates the presence of multiple and diverse microorganisms. Prostate, 2008. 68(3): p. 306-20. [DOI:10.1002/pros.20680]
30. Ittmann, M., Anatomy and Histology of the Human and Murine Prostate. Cold Spring Harb Perspect Med, 2018. 8(5): p. a030346. [DOI:10.1101/cshperspect.a030346]
31. McNeal, J.E., Origin and evolution of benign prostatic enlargement. Invest Urol, 1978. 15(4): p. 340-5.
32. McNeal, J.E., The prostate gland: morphology and pathobiology. Monogr. Urol., 1988. 9: p. 36-54.
33. Hammerich, K.H., G.E. Ayala, and T.M. Wheeler, Anatomy of the prostate gland and surgical pathology of prostate cancer. Cambridge University, Cambridge, 2009: p. 1-10. [DOI:10.1017/CBO9780511551994.003]
34. Lee, C.H., O. Akin-Olugbade, and A. Kirschenbaum, Overview of prostate anatomy, histology, and pathology. Endocrinol Metab Clin North Am, 2011. 40(3): p. 565-75, viii-ix. [DOI:10.1016/j.ecl.2011.05.012]
35. Fine, S.W. and V.E. Reuter, Anatomy of the prostate revisited: implications for prostate biopsy and zonal origins of prostate cancer. Histopathology, 2012. 60(1): p. 142-152. [DOI:10.1111/j.1365-2559.2011.04004.x]
36. Lee, C.H., O. Akin-Olugbade, and A. Kirschenbaum, Overview of prostate anatomy, histology, and pathology. Endocrinology and Metabolism Clinics, 2011. 40(3): p. 565-575. [DOI:10.1016/j.ecl.2011.05.012]
37. IARC, W., Fact sheets Cancers [Internet]. 2018.
38. Gann, P.H., Risk factors for prostate cancer. Rev Urol, 2002. 4 Suppl 5(Suppl 5): p. S3-S10.
39. Bostwick, D.G., et al., Human prostate cancer risk factors. Cancer, 2004. 101(10 Suppl): p. 2371-490. [DOI:10.1002/cncr.20408]
40. Perdana, N.R., et al., The Risk Factors of Prostate Cancer and Its Prevention: A Literature Review. Acta Med Indones, 2016. 48(3): p. 228-238.
41. Huncharek, M., et al., Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. American journal of public health, 2010. 100(4): p. 693-701. [DOI:10.2105/AJPH.2008.150508]
42. Nowalk, A. and M. Green, Epstein-Barr Virus. Microbiol Spectr, 2016. 4(3): p. 127-134. [DOI:10.1128/microbiolspec.DMIH2-0011-2015]
43. Tselis, A.C. and H.B. Jenson, Epstein-Barr virus. 2006: Taylor & Francis New York:. [DOI:10.3109/9781420014280]
44. Thompson, M.P. and R. Kurzrock, Epstein-Barr virus and cancer. Clin Cancer Res, 2004. 10(3): p. 803-21. [DOI:10.1158/1078-0432.CCR-0670-3]
45. Cohen, J.I., Epstein-Barr virus infection. N Engl J Med, 2000. 343(7): p. 481-92. [DOI:10.1056/NEJM200008173430707]
46. Middeldorp, J.M., et al., Pathogenic roles for Epstein-Barr virus (EBV) gene products in EBV-associated proliferative disorders. Crit Rev Oncol Hematol, 2003. 45(1): p. 1-36. [DOI:10.1016/S1040-8428(02)00078-1]
47. Aitken, C., et al., Heterogeneity within the Epstein-Barr virus nuclear antigen 2 gene in different strains of Epstein-Barr virus. Journal of general virology, 1994. 75(1): p. 95-100. [DOI:10.1099/0022-1317-75-1-95]
48. Bánáti, F., A. Koroknai, and K. Szenthe, Terminal Repeat Analysis of EBV Genomes, in Epstein Barr Virus. 2017, Springer. p. 169-177. [DOI:10.1007/978-1-4939-6655-4_12]
49. Cheung, A. and E. Kieff, Long internal direct repeat in Epstein-Barr virus DNA. J Virol, 1982. 44(1): p. 286-94. [DOI:10.1128/jvi.44.1.286-294.1982]
50. Fruehling, S., et al., Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein-Barr virus latency. Journal of virology, 1998. 72(10): p. 7796-7806. [DOI:10.1128/JVI.72.10.7796-7806.1998]
51. Tsao, S.W., et al., The role of Epstein-Barr virus in epithelial malignancies. J Pathol, 2015. 235(2): p. 323-33. [DOI:10.1002/path.4448]
52. Ali, S.H.M. and S.H.M. Al-Alwany, Molecular localization of Epstein Barr virus and Rb tumor suppressor gene expression in tissues from prostatic adenocarcinoma and benign prostatic hyperplasia. Iraqi journal of biotechnology, 2014. 13(2).
53. Hui-Yuen, J., et al., Establishment of Epstein-Barr virus growth-transformed lymphoblastoid cell lines. Journal of visualized experiments: JoVE, 2011(57): p. 3321. [DOI:10.3791/3321]
54. Moppert, J., et al., The concentration of IL-6, TNF-α, s-ICAM-1, and EBV DNA load-predictive factors of hepatological complications in children with infectious mononucleosis. A pilot study. Pediatria Polska-Polish Journal of Paediatrics, 2023. 98(1): p. 43-51. [DOI:10.5114/polp.2023.126111]
55. Jiang, Z., et al., RB1 and p53 at the crossroad of EMT and triple-negative breast cancer. Cell cycle, 2011. 10(10): p. 1563-1570. [DOI:10.4161/cc.10.10.15703]
56. Iwatsuki, K., et al., A spectrum of clinical manifestations caused by host immune responses against Epstein-Barr virus infections. Acta Med Okayama, 2004. 58(4): p. 169-80.
57. Nevins, J.R., The Rb/E2F pathway and cancer. Hum Mol Genet, 2001. 10(7): p. 699-703. [DOI:10.1093/hmg/10.7.699]
58. AbdullahAbbas, A. and I.H. Saadoon, Relation of Epstein Barr virus with interleukin-10 Levelamongmen with Prostate Cancer in Ramadi City. Indian Journal of Forensic Medicine & Toxicology, 2020. 14(2).
59. Tektook, N.K., M.F. Threafand, and E.Y. Pirko, Helicobacter pylori Infected in Iraqi Diabetic Patients (Type 2) and its Correlated with level of Proinflammatory Cytokine-17. Research Journal of Pharmacy and Technology, 2019. 12(9): p. 4255-4258. [DOI:10.5958/0974-360X.2019.00731.5]
60. Liberati, A., J. Tetzlaff, and D.G. Altman, Group P 2009 Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Available: http://journals. plos. org/plosmedicine/article.
61. Morgan, R.L., et al., Evaluation of the risk of bias in non-randomized studies of interventions (ROBINS-I) and the 'target experiment' concept in studies of exposures: Rationale and preliminary instrument development. Environ Int, 2018. 120: p. 382-387. [DOI:10.1016/j.envint.2018.08.018]
62. Sterne, J.A., et al., ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ, 2016. 355: p. i4919. [DOI:10.1136/bmj.i4919]
63. Grinstein, S., et al., Demonstration of Epstein-Barr virus in carcinomas of various sites. Cancer research, 2002. 62(17): p. 4876-4878.
64. Whitaker, N.J., et al., Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer. Prostate, 2013. 73(3): p. 236-41. [DOI:10.1002/pros.22562]
65. Ali, S.H.M. and S.H.M. Al-Alwany, Molecular localization of Epstein Barr virus and Rb tumor suppressor gene expression in tissues from prostatic adenocarcinoma and benign prostatic hyperplasia. Iraqi Journal of Biotechnology, 2014. 13(2-2): p. 161-172.
66. Wetterauer, C., et al., Early development of human lymphomas in a prostate cancer xenograft program using triple knock-out immunocompromised mice. Prostate, 2015. 75(6): p. 585-92. [DOI:10.1002/pros.22939]
67. Taurozzi, A.J., et al., Spontaneous development of Epstein-Barr Virus associated human lymphomas in a prostate cancer xenograft program. PLoS One, 2017. 12(11): p. e0188228. [DOI:10.1371/journal.pone.0188228]
68. Mezher, M.N. and A.A.H. Auda, Relationship of Human Papilloma Virus (HPV) and Epstein Barr Virus (EBV) with Prostate Cancer in AL-Najaf Governorate. Research Journal of Pharmacy and Technology, 2017. 10(10): p. 3283-3288. [DOI:10.5958/0974-360X.2017.00582.0]
69. Malekshahi, S.S., et al., Epstein-Barr and BK virus in cancerous and noncancerous prostate tissue. Future Virology, 2020. 15(1): p. 13-17. [DOI:10.2217/fvl-2019-0140]
70. AbdullahAbbas, A. and I.H. Saadoon, Relation of Epstein Barr virus with interleukin-10 Levelamongmen with Prostate Cancer in Ramadi City. Indian Journal of Forensic Medicine & Toxicology, 2020. 14(2): p. 2476-2480.
71. Taha, Z.N., I.H. Saadoon, and A.M. Hadi, Detection of epstein-barr virus in patients with prostate cancer and benign prostatic hyperplasia. Biochem. Cell. Arch. 20(2): p. 4443-4446.
72. Al-Ramahy, A.A.H., Detection of Epstein-Barr virus in prostate tissue from prostatic cancer patients in Iraq. Biomedical and Biotechnology Research Journal (BBRJ), 2021. 5(2): p. 180. [DOI:10.4103/bbrj.bbrj_57_21]
73. Nahand, J.S., et al., Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer. BMC Cancer, 2021. 21(1): p. 926. [DOI:10.1186/s12885-021-08658-y]
74. Ahmed, K., et al., Detection and characterization of latency stage of EBV and histopathological analysis of prostatic adenocarcinoma tissues. Sci Rep, 2022. 12(1): p. 10399. [DOI:10.1038/s41598-022-14511-4]
75. Ennaji, Y., et al., Human Papillomavirus and Epstein-Barr virus co-infection in Prostate Cancer: Observational Study. Bulletin of National Institute of Health Sciences, 2023. 141(6): p. 3455-3464.
76. Kiś, J., et al., Can the Epstein-Barr Virus Play a Role in the Development of Prostate Cancer? Cancers, 2024. 16(2): p. 328. [DOI:10.3390/cancers16020328]
77. Klein, E.A. and R. Silverman, Inflammation, infection, and prostate cancer. Curr Opin Urol, 2008. 18(3): p. 315-9. [DOI:10.1097/MOU.0b013e3282f9b3b7]
78. Chen, Y. and J. Wei, Identification of Pathogen Signatures in Prostate Cancer Using RNA-seq. PLoS One, 2015. 10(6): p. e0128955. [DOI:10.1371/journal.pone.0128955]
79. Ambalathingal, G.R., et al., BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies. Clin Microbiol Rev, 2017. 30(2): p. 503-528. [DOI:10.1128/CMR.00074-16]
80. Blanco, R., et al., Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Cervical Cancer: Epidemiology, Mechanisms and Perspectives. Pathogens, 2020. 9(9): p. 685. [DOI:10.3390/pathogens9090685]
81. Nahand, J.S., et al., Possible role of HPV/EBV coinfection in anoikis resistance and development in prostate cancer. BMC Cancer, 2021. 21(1). [DOI:10.1186/s12885-021-08658-y]
82. Guo, L., et al., Epstein-Barr virus oncoprotein LMP1 mediates survivin upregulation by p53 contributing to G1/S cell cycle progression in nasopharyngeal carcinoma. Int J Mol Med, 2012. 29(4): p. 574-80. [DOI:10.3892/ijmm.2012.889]
83. Henderson, S., et al., Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell, 1991. 65(7): p. 1107-15. [DOI:10.1016/0092-8674(91)90007-L]
84. Kakavandi, E., et al., Anoikis resistance and oncoviruses. J Cell Biochem, 2018. 119(3): p. 2484-2491. [DOI:10.1002/jcb.26363]
85. Kim, Y.N., et al., Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol, 2012. 2012: p. 306879. [DOI:10.1155/2012/306879]
Add your comments about this article : Your username or Email:
CAPTCHA
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2025 All Rights Reserved | Iranian Journal of Blood and Cancer

Designed & Developed by : Yektaweb