Viral microbiome of prostate tissue in benign prostatic hyperplasia and prostate cancer
https://doi.org/10.17650/1726-9776-2025-21-1-25-34
Abstract
Aim. To evaluate the incidence of various viruses in prostate tissue in benign prostatic hyperplasia (BPH) and prostate cancer (PCa).
Materials and methods. The study included 145 patients who were operated on for BPH (n = 79) or PCa (n = 66) in the period between 2019 and 2023. Real-time polymerase chain reaction was performed in the obtained samples of surgical material to determine the presence of human papillomavirus (HPV), herpes simplex viruses type 1 and 2, cytomegalovirus (CMV), Epstein–Barr virus (EBV), herpes virus type 6 (HHV-6).
Results. Mean age of patients was 68.2 years. Viruses in prostate tissue were found in 40.7 % of patients in the total cohort: in 35.4 % of patients with BPH and in 47.0 % of patients with PCa (p = 0.159). The most common virus detected in the total cohort of patients was EBV which was found in 18.6 % of patients: in 16.5 % of patients with BPH and in 21.2 % of patients with PCa (p = 0.464). The second most common was HHV-6 (9.0 % of patients of the total cohort: 19.7 % of patients with PCa and in 0 % with BPH, p <0.001), and the third was CMV (7.6 % of patients: 2.5 % of patients with BPH and 13.6 % of patients with PCa, p = 0.027). When combining all HPV types, the prevalence of HPV was 10.3 %, but individual subtypes were found in isolated cases and their incidence in the total cohort did not exceed 2.1 %. The incidence of HPV (all types) was 16.5 % in patients with BPH and 3.0 % in patients with PCa (p = 0.018).
Conclusion. In patients with prostate diseases, almost half of the cases have viral infection localized in the prostate tissue. CMV and HHV-6 are the most common in patients with PCa. The latter was not found in patients with BPH. EBV is equally represented among patients with BPH and PCa.
About the Authors
A. A. KamalovRussian Federation
Faculty of Fundamental Medicine, Department of Urology and Andrology Lomonosov MSU.
Build. 10, 27 Lomonosovskiy Prospekt, Moscow 119192; 1 Leninskie Gory, Moscow 119991
Competing Interests:
The authors declare no conflict of interest
L. M. Mikhaleva
Russian Federation
3 Tsyurupy St., Moscow 117418; 42 Lobachevskogo St., Moscow 119415
Competing Interests:
The authors declare no conflict of interest
V. K. Karpov
Russian Federation
Faculty of Fundamental Medicine, Department of Urology and Andrology Lomonosov MSU.
Build. 10, 27 Lomonosovskiy Prospekt, Moscow 119192; 1 Leninskie Gory, Moscow 119991; 42 Lobachevskogo St., Moscow 119415
Competing Interests:
The authors declare no conflict of interest
D. A. Okhobotov
Russian Federation
Faculty of Fundamental Medicine, Department of Urology and Andrology Lomonosov MSU.
Build. 10, 27 Lomonosovskiy Prospekt, Moscow 119192; 1 Leninskie Gory, Moscow 119991
Competing Interests:
The authors declare no conflict of interest
T. B. Takhirzade
Russian Federation
42 Lobachevskogo St., Moscow 119415
Competing Interests:
The authors declare no conflict of interest
A. M. Pshikhachev
Russian Federation
Faculty of Fundamental Medicine, Department of Urology and Andrology Lomonosov MSU.
Build. 10, 27 Lomonosovskiy Prospekt, Moscow 119192; 1 Leninskie Gory, Moscow 119991; 42 Lobachevskogo St., Moscow 119415
Competing Interests:
The authors declare no conflict of interest
O. Yu. Nesterova
Russian Federation
Faculty of Fundamental Medicine, Department of Urology and Andrology Lomonosov MSU.
Build. 10, 27 Lomonosovskiy Prospekt, Moscow 119192; 1 Leninskie Gory, Moscow 119991
Competing Interests:
The authors declare no conflict of interest
B. M. Shaparov
Russian Federation
1 Leninskie Gory, Moscow 119991; 42 Lobachevskogo St., Moscow 119415
Competing Interests:
The authors declare no conflict of interest
A. A. Strigunov
Russian Federation
Faculty of Fundamental Medicine, Department of Urology and Andrology Lomonosov MSU.
Build. 10, 27 Lomonosovskiy Prospekt, Moscow 119192; 1 Leninskie Gory, Moscow 119991
Competing Interests:
The authors declare no conflict of interest
V. V. Pechnikova
Russian Federation
3 Tsyurupy St., Moscow 117418; 42 Lobachevskogo St., Moscow 119415
Competing Interests:
The authors declare no conflict of interest
O. A. Osmanov
Russian Federation
Omar Aslanovich Osmanov - Faculty of Fundamental Medicine, Department of Urology and Andrology.
1 Leninskie Gory, Moscow 119991
Competing Interests:
The authors declare no conflict of interest
References
1. Banerjee S., Alwine J.C., Wei Z. et al. Microbiome signatures in prostate cancer. Carcinogenesis 2019;40(6):749–64. DOI: 10.1093/carcin/bgz008
2. Feng Y., Ramnarine V.R., Bell R. et al. Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer. BMC Genomics 2019;20(1):146. DOI: 10.1186/s12864-019-5457-z
3. Sfanos K.S., Sauvageot J., Fedor H.L. 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):306–20. DOI: 10.1002/pros.20680
4. Lang B., Cao C., Zhao X. et al. Genomic alterations related to HPV infection status in a cohort of Chinese prostate cancer patients. Eur J Med Res 2023;28(1):239. DOI: 10.1186/s40001-023-01207-2
5. Caini S., Gandini S., Dudas M. et al. Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis. Cancer Epidemiol 2014;38(4):329–38. DOI: 10.1016/j.canep.2014.06.002
6. Grinstein S., Preciado M.V., Gattuso P. et al. Demonstration of Epstein–Barr virus in carcinomas of various sites. Cancer Res 2002;62(17):4876–8.
7. Smelov V., Bzhalava D., Arroyo Mühr L.S. et al. Detection of DNA viruses in prostate cancer. Scientific Rep 2016;6:25235. DOI: 10.1038/srep25235
8. Abidi S.H., Bilwani F., Ghias K., Abbas F. Viral etiology of prostate cancer: Genetic alterations and immune response. A literature review. Int J Surg 2018;52:136–40. DOI: 10.1016/j.ijsu.2018.02.050
9. Hrbacek J., Urban M., Hamsikova E. et al. Thirty years of research on infection and prostate cancer: no conclusive evidence for a link. A systematic review. Urol Oncol 2013;31(7):951–65. DOI: 10.1016/j.urolonc.2012.01.013
10. Cancer Taday. Available at: https://gco.iarc.fr/today/home
11. Smelov V., Arroyo Mühr L.S., Bzhalava D. et al. Metagenomic sequencing of expressed prostate secretions. J Med Virol 2014;86(12):2042–8. DOI: 10.1002/jmv.23900
12. Ala-Almohadesin A., Mohammadbeygi M., Bahavar A. et al. Molecular detection of pathogens causing sexually transmissible infections in patients with prostate cancer and hyperplasia by quantitative taqman real-time PCR assay. Clin Lab 2019;65(7). DOI: 10.7754/Clin.Lab.2019.181243
13. Sarkar P., Malik S., Banerjee A. et al. Differential microbial signature associated with benign prostatic hyperplasia and prostate cancer. Fron Cell Infect Microbiol 2022;12:894777. DOI: 10.3389/fcimb.2022.894777
14. Nellessen T., Ebner B., Pyrgidis N. et al. Characterization of human papilloma virus in prostate cancer patients undergoing radical prostatectomy-A prospective study of 140 patients. Viruses 2023;15(6):1264. DOI: 10.3390/v15061264
15. Basulto-Martínez M., Flores-Tapia J.P., Conde-Ferráez L. et al. Molecular detection of human papillomavirus among patients with benign prostatic hyperplasia and prostate cáncer. Arch Esp Urol 2022;75(1):27–33.
16. Pereira N.M., Martins E.A.C., Quintela M.G. et al. Presence of HPV in prostate tissue from patients submitted to prostate biopsy. Acta Cir Bras 2023;37(12):e371205. DOI: 10.1590/acb371205
17. Ghasemian E., Monavari S.H.R., Irajian G.R. et al. Evaluation of human papillomavirus infections in prostatic disease: a cross-sectional study in Iran. Asian Pac J Cancer Prev 2013;14(5):3305–8. DOI: 10.7314/apjcp.2013.14.5.3305
18. May M., Kalisch R., Hoschke B. et al. Detection of papillomavirus DNA in the prostate: a virus with underestimated clinical relevance? Urologe A 2008;47(7):846–52. DOI: 10.1007/s00120-008-1694-5
19. Tsydenova I.A., Ibragimova M.K., Tsyganov M.M., Litviakov N.V. Human papillomavirus and prostate cancer: systematic review and meta-analysis. Sci Rep 2023;13(1):16597. DOI: 10.1038/s41598-023-43767-7
20. Martinez-Fierro M.L., Leach R.J., Gomez-Guerra L.S. et al. Identification of viral infections in the prostate and evaluation of their association with cancer. BMC Cancer 2010;10:326. DOI: 10.1186/1471-2407-10-326
21. Whitaker N.J., Glenn W.K., Sahrudin A. 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):236–41. DOI: 10.1002/pros.22562
22. Sawaya M., Cordina-Duverger E., Lamy P.J. et al. Sexually and non-sexually transmitted infections and the risk of prostate cancer: results from the EPICAP study. Cancer Med 2024;13(1):e6841. DOI: 10.1002/cam4.6841
23. Lawson J.S., Glenn W.K. Multiple pathogens and prostate cancer. Infect Agent Cancer 2022;17(1):23. DOI: 10.1186/s13027-022-00427-1
24. Boldogh I., Baskar J.F., Mar E.C., Huang E.S. Human cytomegalovirus and herpes simplex type 2 virus in normal and adenocarcinomatous prostate glands. J Natl Cancer Inst 1983;70(5):819–26.
25. Klochkova T.G., Andabaev T.T., Samsonov R.B. et al. Analysis of prostate infection with cytomegalovirus in patients with cancer and benign prostatic hyperplasia. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal 2008;8(4):64–70. (In Russ.).
26. Samsonov R.B., Klochkova T.G., Andabekov T.T. et al. Cytomegolovirus infection of the prostate tissue in patients with prostate cancer and benign prostatic hyperplasia. Voprosy onkologii = Problems in Oncology 2010;52(2 Appendix, Abstracts of the 6th Russian Conference on Basic Oncology):39–40. (In Russ.).
27. Bouezzedine F., El Baba R., Haidar Ahmad S., Herbein G. Polyploid giant cancer cells generated from human cytomegalovirus-infected prostate epithelial cells. Cancers 2023;15(20):4994. DOI: 10.3390/cancers15204994
28. Blaheta R.A., Weich E., Marian D. et al. Human cytomegalovirus infection alters PC3 prostate carcinoma cell adhesion to endothelial cells and extracellular matrix. Neoplasia 2006;8(10):807–16. DOI: 10.1593/neo.06379
29. Doniger J., Muralidhar S., Rosenthal L.J. Human cytomegalovirus and human herpesvirus 6 genes that transform and transactivate. Clin Microbiol Rev 1999;12(3):367–82. DOI: 10.1128/CMR.12.3.367
30. Gabrielli L., Balboni A., Borgatti E.C. et al. Inherited Chromosomally integrated human herpesvirus 6: laboratory and clinical features. Microorganisms 2023;11(3):548. DOI: 10.3390/microorganisms11030548
31. Mardente S., Romeo M.A., Asquino A. et al. HHV-6A infection of papillary thyroid cancer cells induces several effects related to cancer progression. Viruses 2023;15(10):2122. DOI: 10.3390/v15102122
32. Sarshari B., Mohebbi S.R., Ravanshad M. et al. Detection and quantification of Epstein–Barr virus, cytomegalovirus, and human herpesvirus-6 in stomach frozen tissue of chronic gastritis and gastric cancer patients. Microbiol Immunol 2022;66(8):379–85. DOI: 10.1111/1348-0421.13013
33. Gulve N., Rudel T. Chlamydia trachomatis and human herpesvirus 6 infections in ovarian cancer – Casual or causal? PLoS Pathog 2019;15(11):e1008055. DOI: 10.1371/journal.ppat.1008055
Review
For citations:
Kamalov A.A., Mikhaleva L.M., Karpov V.K., Okhobotov D.A., Takhirzade T.B., Pshikhachev A.M., Nesterova O.Yu., Shaparov B.M., Strigunov A.A., Pechnikova V.V., Osmanov O.A. Viral microbiome of prostate tissue in benign prostatic hyperplasia and prostate cancer. Cancer Urology. 2025;21(1):25-34. (In Russ.) https://doi.org/10.17650/1726-9776-2025-21-1-25-34