EVALUATING THE RELATIONSHIP BETWEEN HUMAN PAPILLOMA VIRUS INFECTIONS, PROSTATE CANCER AND INTERLEUKIN-12 LEVELS
https://doi.org/10.15789/1563-0625-ITR-3021
Abstract
Abstract
Prostate cancer (PC); is the second leading cause of cancer mortality among men. Human papillomavirus (HPV) is the most common cause of cervical cancer, strongly associated with anal and vaginal cancers. Also, interleukin-12 (IL-12) induces antitumor immunity. This study aimed to investigate the role of HPV in PC; and determine its effects on serum IL-12 .
Between 2018 and 2022 in Ahvaz, researchers obtained 55 paraffin samples of malignant prostate lesions and 55 control samples of benign hyperplasia tissues from the prostate. Blood samples were collected from 24 diagnosed cancer patients to assess IL-12 levels before treatment initiation. Additionally, 24 patients with benign prostatic hyperplasia participated as controls. We performed DNA extraction using the phenol-chloroform method and examined the presence of papillomavirus DNA in tissues through Nested-PCR. Subsequently, IL-12 levels in serum were measured using ELISA.
The findings did not show the relationship between HPV and PC; HPV infection was not correlated to the presence of IL-12 secretion. However, with the progression of cancer, the level of IL-12 decreased significantly in patients compared to the control group (P<0.05).
HPV infection can exist in prostate tissue, although this does not mean that it contributes to P.C. development. The most significant strains infecting prostate tissue are types 16 and 18. Compared to the control group and with different Gleason scores, prostate cancer patient's levels of interleukin-12 secretion are significantly lower. One can make effective measures to assess the prognosis, regulate the condition, or aid in treating individuals using this crucial cytokine.
Supporting agencies: The Ahvaz Jundishapur University of Medical Sciences financially supported this study [grant number CRC-9917].
About the Authors
Sadegh Moradi
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Islamic Republic of Iran
Competing Interests:
Islamic Republic of Iran
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
Competing Interests:
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they are not employed by the government agency that has a primary function other than research and, or education.
Mohammad Rashno
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Assistant Professor of Microbiology Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
Mohsen Sarkarian
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Assistant Professor of Urology Department of Urology, School of Medicine, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
Gholam Abbas Kaydani
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Assistant Professor of Medical Virology Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
Ladan Fatahi
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Assistant Professor of Pathology Department of Pathology, School of Medicine,Imam Khomeini Hospital, Golestan Hospital,Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
Maryam Seyedtabib
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Assistant Professor of Biostatistics Department of Biostatistics and Epidemiology, School of Health,Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
Moosa shariffat
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
ali khodadadi
Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Department of Immunology, Faculty of Medicine . Ahvaz Jundishapur University of Medical Sciences , Ahvaz, Iran
References
1. Rosalik, K., C. Tarney, and J. Han, Human papilloma virus vaccination. Viruses, 2021. 13(6): p. 1091.
2. Yu, L., V. Majerciak, and Z.-M. Zheng, HPV16 and HPV18 genome structure, expression, and post-transcriptional regulation. International journal of molecular sciences, 2022. 23(9): p. 4943.
3. Minichsdorfer, C., HPV-associated cancers. memo - Magazine of European Medical Oncology, 2019. 12(4): p. 352-356.
4. Okunade, K.S., Human papillomavirus and cervical cancer. Journal of Obstetrics and Gynaecology, 2020. 40(5): p. 602-608.
5. Russo, G.I., et al., Human papillomavirus and risk of prostate cancer: a systematic review and meta-analysis. The Aging Male, 2020. 23(2): p. 132-138.
6. Videla, S., et al., Incidence and clinical management of oral human papillomavirus infection in men: a series of key short messages. 2014. 12(8): p. 947-957.
7. Bagcchi, S., Harald zur Hausen. The Lancet Infectious Diseases, 2023. 23(9): p. 1001.
8. Amadi, V., N. Nwiabu, and V. Anireh, Case-Based Reasoning System for the Diagnosis and Treatment of Breast, Cervical and Prostate Cancer. SSRG International Journal of Computer Science and Engineering, 2021. 8(8): p. 13-20.
9. Lawson, J.S. and W.K. Glenn, Evidence for a causal role by human papillomaviruses in prostate cancer–a systematic review. Infectious Agents and Cancer, 2020. 15: p. 1-11.
10. Khatami, A., et al., Human papilloma virus (HPV) and prostate cancer (PCa): The potential role of HPV gene expression and selected cellular MiRNAs in PCa development. Microbial pathogenesis, 2022. 166: p. 105503.
11. Croxford, A.L., et al., IL-12-and IL-23 in health and disease. 2014. 25(4): p. 415-421.
12. Negin, F.A., Immunotherapy of Prostate Cancer by a Combination of Treatments Aiming at Activation of OX40 and Intratumoral Production of IL-12. 2022, Université Laval.
13. Habiba, U.e., et al., The multifaceted role of IL-12 in cancer. Advances in Cancer Biology - Metastasis, 2022. 5: p. 100053.
14. Yin, X., et al., AntiTumor mechanism of recombinant murine interleukin-12 vaccine. 2010. 25(3): p. 263-268.
15. Paz, F.G., et al., The relationship between the antitumor effect of the IL-12 gene therapy and the expression of Th1 cytokines in an HPV16-positive murine tumor model. Mediators of Inflammation, 2014. 2014.
16. Berraondo, P., J. Prieto, and G.J.C.g.t. Gonzalez-Aseguinolaza, Advances in interleukin-12 gene therapy for acquired liver diseases. 2009. 9(2): p. 62-71.
17. Mahvi, D., et al., Intratumoral injection of IL-12 plasmid DNA–results of a phase I/IB clinical trial. 2007. 14(8): p. 717.
18. Tugues, S., et al., New insights into IL-12-mediated tumor suppression. Cell Death & Differentiation, 2015. 22(2): p. 237-246.
19. Shi, G., et al., IL-12 gene electrotransfer triggers a change in immune response within mouse tumors. Cancers, 2018. 10(12): p. 498.
20. Torres-Poveda, K., et al., Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia. 2014. 5(4): p. 753.
21. Ma, W., et al., Multi-dose parecoxib provides an immunoprotective effect by balancing T helper 1 (Th1), Th2, Th17 and regulatory T cytokines following laparoscopy in patients with cervical cancer. 2015. 11(4): p. 2999-3008.
22. Bermúdez-Morales, V., et al., IL-10 expression is regulated by HPV E2 protein in cervical cancer cells. 2011. 4(2): p. 369-375.
23. Feng, Q., et al., Th2 type inflammation promotes the gradual progression of HPV-infected cervical cells to cervical carcinoma. 2012. 127(2): p. 412-419.
24. Bermúdez-Morales, V.H., et al., In vivo Antitumor Effect of an HPV-specific Promoter driving IL-12 Expression in an HPV 16-positive Murine Model of Cervical Cancer. 2016. 7(14): p. 1950.
25. Marcuccilli, F., et al., Performance evaluation of Anyplex™ II HPV28 detection kit in a routine diagnostic setting: comparison with the HPV Sign® Genotyping Test. 2015. 217: p. 8-13.
26. Mesri, E.A., et al., Human viral oncogenesis: a cancer hallmarks analysis. 2014. 15(3): p. 266-282.
27. Guma, S., et al., Papillary urothelial carcinoma with squamous differentiation in association with human papilloma virus: case report and literature review. 2016. 4(1): p. 12.
28. Tolstov, Y., et al. Human papillomaviruses in urological malignancies: a critical assessment. in Urologic Oncology: Seminars and Original Investigations. 2014. Elsevier.
29. Yang, L., et al., Worldwide prevalence of human papillomavirus and relative risk of prostate cancer: a meta-analysis. 2015. 5(1): p. 1-10.
30. Nahand, J.S., et al., The assessment of a possible link between HPV‐mediated inflammation, apoptosis, and angiogenesis in Prostate cancer. 2020. 88: p. 106913.
31. Shariat, A., P. Arzani, and M.J.J.S.M.J. Shirali, Studying the Association Between Human Papillomavirus and Prostate Cancer by Immunohistochemistry and PCR Techniques in Ahvaz Hospitals. 2020. 19(4): p. 425-434.
32. Michopoulou, V., et al., Detection of human papillomavirus (HPV) DNA prevalence and p53 codon 72 (Arg72Pro) polymorphism in prostate cancer in a Greek group of patients. 2014. 35(12): p. 12765-12773.
33. Medel-Flores, O., et al., Association between HPV infection and prostate cancer in a Mexican population. 2018. 41(4): p. 781-789.
34. Moghoofei, M., et al., Association between human papillomavirus infection and prostate cancer: A global systematic review and meta‐analysis. Asia‐Pacific Journal of Clinical Oncology, 2019. 15(5): p. e59-e67.
35. Atashafrooz, F. and F. Rokhbakhsh-Zamin, Frequency and type distribution of human papilloma virus in patients with prostate cancer, Kerman, Southeast of Iran. Asian Pacific Journal of Cancer Prevention, 2016. 17(8): p. 3953-3958.
36. Chen, A.C.-H., et al., Human papillomavirus in benign prostatic hyperplasia and prostatic adenocarcinoma patients. 2011. 17(3): p. 613-617.
37. Mahmoudi, S., et al., Prostate cancer and human papillomavirus infection: a recent literature review. Reviews and Research in Medical Microbiology, 2022. 33(2): p. 100-108.
38. Usman, M., et al., Identification of correlation between human papillomavirus and prostate cancer: Bradford Hill Criteria Based Evaluation. 2021.
39. Opeyemi Bello, R., et al., Does Human Papillomavirus Play a Causative Role in Prostate Cancer? A Systematic Review Using Bradford Hill’s Criteria. Cancers, 2023. 15(15): p. 3897.
40. Bae, J.-M.J.E. and health, Human papillomavirus 16 infection as a potential risk factor for prostate cancer: an adaptive meta-analysis. 2015. 37.
41. Guenova, E., et al., IL‐4‐mediated fine tuning of IL‐12p70 production by human DC. 2008. 38(11): p. 3138-3149.
42. Salimu, J., et al., Dominant immunosuppression of dendritic cell function by prostate-cancer-derived exosomes. 2017. 6(1): p. 1368823.
43. Kundu, M., A. Roy, and K.J.P.o.t.N.A.o.S. Pahan, Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12–IFN-γ. 2017. 114(43): p. 11482-11487.
44. Shekar Abi, M., et al., The Evaluation of Serum Levels of IFN-, IL-12 and Percentage of CD4+, CD8+ and NK Cells in Peripheral Blood of Metastatic, Nonmetastatic Breast Cancer Patients and Normal Individuals. 2008. 14(57): p. 113-120.
45. Kovacs, E.J.B. and pharmacotherapy, The serum levels of IL-12 and IL-16 in cancer patients. Relation to the tumour stage and previous therapy. 2001. 55(2): p. 111-116.
46. Murakami, S., et al., Serum interleukin-12 levels in patients with gastric cancer. 2004. 34(12): p. 1014-1019.
47. Jebreel, A., et al., Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer. 2007. 121(3): p. 246.
Supplementary files
|
1. Figure 1 | |
| Subject | ||
| Type | Research Instrument | |
Download
(62KB)
|
Indexing metadata ▾ | |
|
|
2. Table 1 | |
| Subject | ||
| Type | Research Instrument | |
Download
(55KB)
|
Indexing metadata ▾ | |
|
|
3. Table 2 | |
| Subject | ||
| Type | Research Instrument | |
Download
(58KB)
|
Indexing metadata ▾ | |
|
|
4. Table 3 | |
| Subject | ||
| Type | Research Instrument | |
Download
(54KB)
|
Indexing metadata ▾ | |
|
5. 3021 | |
| Subject | ||
| Type | Other | |
Download
(68KB)
|
Indexing metadata ▾ | |
Review
For citations:
Moradi S., Rashno M., Sarkarian M., Kaydani G., Fatahi L., Seyedtabib M., shariffat M., khodadadi a. EVALUATING THE RELATIONSHIP BETWEEN HUMAN PAPILLOMA VIRUS INFECTIONS, PROSTATE CANCER AND INTERLEUKIN-12 LEVELS. Medical Immunology (Russia). https://doi.org/10.15789/1563-0625-ITR-3021
Views:
1
Email this article 