Iranian Journal of Pathology

Association of Human Papilloma Virus and Epstein-Barr Virus with Ovarian Cancer in Shiraz, Southwestern Iran

Document Type : Original Research

Authors

Mohammad Reza Shokouh 1
Akbar Safaie 2
Afagh Moattari 3
Jamal Sarvari 1, 4

1 Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Pathology Department, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Bacteriology & Virology, School of Medicine, Shiraz University of Medical Sciences Shiraz, Iran

4 Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

https://doi.org/10.30699/ijp.2020.119681.2306
Abstract
Background & Objective:  Ovarian cancer is one of the most common cancers amongst women. The association of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) with ovarian cancer is inconclusive; therefore, the aims of this study were to evaluate the frequency of HPV and EBV in malignant, borderline, benign and normal ovarian tissues.
Methods:  In this case-control study, 205 Paraffin-embedded ovarian tissue specimens including 68 malignant, 27 borderline, 65 benign, and 45 normal tissues were included from December 2014 to January 2018 and subjected to DNA extraction. The β-globin gene was amplified using PCR to confirm the quality of the extracted DNA. The genomes of HPV (genotypes 16 and 18) and EBV were identified, using specific primers by PCR.
Results:  The mean age of participants was 43.42 ± 15.4 years. The frequency of HPV was statistically significant between malignant versus benign (p =0.02) and control groups (p =0.002), but not with borderline tumor group (p =0.78). Amongst HPV infected samples, 1 (4.5%) and 14 (63.6%) samples were infected with types 16 and 18, respectively. Also 4 (18.2 %) samples were infected with both genotypes. Eleven samples including 7(10.3%) malignant, 1 (3.7%) borderline, 3 (4.6%) benign and none (0%) of normal control groups were infected with EBV, which was statistically different between malignant and the normal control group (p =0.03).
Conclusion:  The results of our study showed the possible role of high risk HPVs as well as EBV in pathogenesis of ovarian cancer, and further studies are recommended to confirm these findings.

Keywords

Epstein-Barr virus
Human Papillomavirus
Ovarian Cancer

Subjects

  1. Global Burden of Disease Cancer C, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2017;3(4):524-48. [DOI:10.1001/jamaoncol.2016.5688] [PMID] [PMCID]
  2. Arab M, Noghabaei G. Ovarian cancer incidence in Iran and the world. Reports of Radiotherapy and Oncology. 2013;1(2).
  3. Boyd J. BRCA: the breast, ovarian, and other cancer genes. Gynecologic oncology. 2001;80(3):337-40. [DOI:10.1006/gyno.2001.6131] [PMID]
  4. Alibek K, Kakpenova A, Mussabekova A, Sypabekova M, Karatayeva N. Role of viruses in the development of breast cancer. Infectious agents and cancer. 2013;8(1):32. [DOI:10.1186/1750-9378-8-32] [PMID] [PMCID]
  5. Piroozmand A, Zadeh SMM, Madani A, Soleimani R, Nedaeinia R, Niakan M, et al. The association of high risk human papillomaviruses in patients with cervical cancer: an evidence based study on patients with squamous cell dysplasia or carcinoma for evaluation of 23 human papilloma virus genotypes. Jundishapur journal of microbiology. 2016;9(4). [DOI:10.5812/jjm.32728] [PMID] [PMCID]
  6. Schiller JT, Day PM, Kines RC. Current understanding of the mechanism of HPV infection. Gynecologic oncology. 2010;118(1):S12-S7. [DOI:10.1016/j.ygyno.2010.04.004] [PMID] [PMCID]
  7. Conway MJ, Alam S, Ryndock EJ, Cruz L, Christensen ND, Roden RB, et al. Tissue-spanning redox gradient-dependent assembly of native human papillomavirus type 16 virions. Journal of virology. 2009;83(20):10515-26. [DOI:10.1128/JVI.00731-09] [PMID] [PMCID]
  8. Radley D, Saah A, Stanley M. Persistent infection with human papillomavirus 16 or 18 is strongly linked with high-grade cervical disease. Human vaccines & immunotherapeutics. 2016;12(3):768-72. [DOI:10.1080/21645515.2015.1088616] [PMID] [PMCID]
  9. Mahmoudvand S, Safaei A, Erfani N, Sarvari J. Presence of human papillomavirus DNA in colorectal cancer tissues in Shiraz, Southwest Iran. Asian Pac J Cancer Prev. 2015;16(17):7883-7. [DOI:10.7314/APJCP.2015.16.17.7883] [PMID]
  10. Jalilvand S, Shoja Z, Hamkar R. Human papillomavirus burden in different cancers in Iran: a systematic assessment. Asian Pac J Cancer Prev. 2014;15(17):7029-35. [DOI:10.7314/APJCP.2014.15.17.7029] [PMID]
  11. Mohammadpour B, ROUHI S, Khodabandehloo M, Moradi M. Prevalence and Association of Human Papillomavirus with Esophageal Squamous Cell Carcinoma in Iran: A Systematic Review and Meta-Analysis. Iranian journal of public health. 2019;48(7):1215. [DOI:10.18502/ijph.v48i7.2943]
  12. Farzaneh F, Nadji SA, Khosravi D, Hosseini MS, Bahremani MH, Chehrazi M, et al. Lack of HPV in Benign and Malignant Epithelial Ovarian Tumors in Iran. Asian Pacific journal of cancer prevention: APJCP. 2017;18(5):1233.
  13. Dadashi M, Eslami G, Faghihloo E, Pourmohammad A, Hosseini J, Taheripanah R, et al. Detection of human papilloma virus type 16 in epithelial ovarian tumors samples. Archives of Clinical Infectious Diseases. 2017;12(1). [DOI:10.5812/archcid.39666]
  14. Mui U, Haley C, Tyring S. Viral oncology: molecular biology and pathogenesis. Journal of clinical medicine. 2017;6(12):111. [DOI:10.3390/jcm6120111] [PMID] [PMCID]
  15. Arbach H, Viglasky V, Lefeu F, Guinebretiere J-M, Ramirez V, Bride N, et al. Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol). Journal of virology. 2006;80(2):845-53. [DOI:10.1128/JVI.80.2.845-853.2006] [PMID] [PMCID]
  16. Zuo L, Yue W, Du S, Xin S, Zhang J, Liu L, et al. An update: Epstein-Barr virus and immune evasion via microRNA regulation. Virol Sin. 2017;32(3):175-87. [DOI:10.1007/s12250-017-3996-5] [PMID] [PMCID]
  17. Bakhtiyrizadeh S, Hosseini SY, Yaghobi R, Safaei A, Sarvari J. Almost complete lack of human cytomegalovirus and human papillomaviruses genome in benign and malignant breast lesions in Shiraz, Southwest of Iran. Asian Pacific journal of cancer prevention: APJCP. 2017;18(12):3319.
  18. Joharinia N, Farhadi A, Hosseini SY, Safaei A, Sarvari J. Association of HPV16 and 18 genomic copies with histological grades of cervical lesions. VirusDisease. 2019;30(3):387-93. [DOI:10.1007/s13337-019-00545-2] [PMID]
  19. Joharinia N, Faghihinezhad S, Seyedi K, Farhadi A, Hosseini SY, Safaei A, et al. Co-existing of HSV1/2 or EBV Infection with the Presence of High-Risk HPV DNA in Cervical Lesions in the Southwest of Iran. Asian Pac J Cancer Prev, . 2020;21(5):1459-64. [DOI:10.31557/APJCP.2020.21.5.1459] [PMID]
  20. Idahl A, Lundin E, Elgh F, Jurstrand M, Møller JK, Marklund I, et al. Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus, and polyomavirus are not detectable in human tissue with epithelial ovarian cancer, borderline tumor, or benign conditions. American journal of obstetrics and gynecology. 2010;202(1):71. e1-. e6. [DOI:10.1016/j.ajog.2009.07.042] [PMID]
  21. Wu Q, Guo M, Lu Z, Li T, Qiao H, Ke Y. Detection of human papillomavirus-16 in ovarian malignancy. British journal of cancer. 2003;89(4):672. [DOI:10.1038/sj.bjc.6601172] [PMID] [PMCID]
  22. Al-Shabanah OA, Hafez MM, Hassan ZK, Sayed-Ahmed MM, Abozeed WN, Al-Rejaie SS, et al. Human papillomavirus genotyping and integration in ovarian cancer Saudi patients. Virology journal. 2013;10(1):343. [DOI:10.1186/1743-422X-10-343] [PMID] [PMCID]
  23. Hammou RA, Benhessou M, Bouziyane A, Hassou N, Benhchekroun MN, Bessi H, et al. Oncogenic Human Papillomavirus involvement in epithelial ovarian carcinoma among women in Morocco. Bioinformation. 2019;15(1):55. [DOI:10.6026/97320630015055] [PMID] [PMCID]
  24. Hassan ZK, Hafez MM, Kamel MM, Zekri ARN. Human papillomavirus genotypes and methylation of CADM1, PAX1, MAL and ADCYAP1 genes in epithelial ovarian cancer patients. Asian Pacific journal of cancer prevention: APJCP. 2017;18(1):169.
  25. Mahmood FM, Kadhim HS, Al Khuzaee LRM. Detection of human papillomavirus-16 e6-oncoprotein in epithelial ovarian tumors samples of iraqi patients. Jundishapur journal of microbiology. 2014;7(9). [DOI:10.5812/jjm.11945] [PMID] [PMCID]
  26. Bilyk O, Pande N, Buchynska L. Analysis of P53, P16INK4A, PRB and cyclin D1 expression and human papillomavirus in primary ovarian serous carcinoma. Experimental oncology. 2011.
  27. Atalay F, Taskiran C, Taner MZ, Pak I, Or M, Tuncer S. Detection of human papillomavirus DNA and genotyping in patients with epithelial ovarian carcinoma. Journal of Obstetrics and Gynaecology Research. 2007;33(6):823-8. [DOI:10.1111/j.1447-0756.2007.00663.x] [PMID]
  28. Li T, Lu ZM, Guo M, Wu QJ, Chen KN, Xing HP, et al. p53 codon 72 polymorphism (C/G) and the risk of human papillomavirus‐associated carcinomas in China. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2002;95(12):2571-6. [DOI:10.1002/cncr.11008] [PMID]
  29. Ingerslev K, Hogdall E, Skovrider-Ruminski W, Schnack TH, Karlsen MA, Nedergaard L, et al. High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population. Infectious agents and cancer. 2016;11(1):39. [DOI:10.1186/s13027-016-0087-4] [PMID] [PMCID]
  30. Wentzensen N, du Bois A, Kommoss S, Pfisterer J, von Knebel Doeberitz M, Schmidt D, et al. No metastatic cervical adenocarcinomas in a series of p16INK4a-positive mucinous or endometrioid advanced ovarian carcinomas: an analysis of the AGO Ovarian Cancer Study Group. International Journal of Gynecological Pathology. 2008;27(1):18-23. [DOI:10.1097/pgp.0b013e318074b83f] [PMID]
  31. Shanmughapriya S, Senthilkumar G, Vinodhini K, Das B, Vasanthi N, Natarajaseenivasan K. Viral and bacterial aetiologies of epithelial ovarian cancer. European journal of clinical microbiology & infectious diseases. 2012;31(9):2311-7. [DOI:10.1007/s10096-012-1570-5] [PMID]
  32. Zimna K, Poreba E, Kedzia W, Goździcka-Józefiak A, Kedzia H. Human papillomavirus (HPV) in upper genital tract carcinomas of women. European journal of gynaecological oncology. 1997;18(5):415-7.
  33. Zhang P-P, Zhou L, Cao J-S, Li Y-P, Zeng Z, Sun N, et al. Possible Epithelial Ovarian Cancer Association with HPV18 or HPV33 Infection. Asian Pacific journal of cancer prevention: APJCP. 2016;17(6):2959-64.
  34. Yang H-J, Liu VW, Tsang PC, Yip AM, Ng T-Y, Cheung AN, et al. Comparison of human papillomavirus DNA levels in gynecological cancers: implication for cancer development. Tumor biology. 2003;24(6):310-6. [DOI:10.1159/000076463] [PMID]
  35. Malisic E, Jankovic R, Jakovljevic K. Detection and genotyping of human papillomaviruses and their role in the development of ovarian carcinomas. Archives of gynecology and obstetrics. 2012;286(3):723-8. [DOI:10.1007/s00404-012-2367-6] [PMID]
  36. Ingerslev K, Høgdall E, Skovrider-Ruminski W, Schnack TH, Lidang M, Høgdall C, et al. The prevalence of EBV and CMV DNA in epithelial ovarian cancer. Infectious agents and cancer. 2019;14(1):7. [DOI:10.1186/s13027-019-0223-z] [PMID] [PMCID]
  37. Pandya D, Mariani M, McHugh M, Andreoli M, Sieber S, He S, et al. Herpes virus microRNA expression and significance in serous ovarian cancer. PloS one. 2014;9(12):e114750. [DOI:10.1371/journal.pone.0114750] [PMID] [PMCID]
  38. Littman AJ, Rossing MA, Madeleine MM, Tang M-TC, Yasui Y. Association between late age at infectious mononucleosis, Epstein-Barr virus antibodies, and ovarian cancer risk. Scandinavian journal of infectious diseases. 2003;35(10):728-35. [DOI:10.1080/00365540310016556] [PMID]
  39. Dowran R, Joharinia N, Safaei A, Bakhtiyarizadeh S, Soleimani AA, Alizadeh R, et al. No detection of EBV, BKV and JCV in breast cancer tissue samples in Iran. BMC research notes. 2019;12(1):171. [DOI:10.1186/s13104-019-4178-3] [PMID] [PMCID]
Iranian Journal of Pathology
Volume 15, Issue 4
Autumn 2020
Pages 292-298

  • Receive Date 28 January 2020
  • Revise Date 21 July 2020
  • Accept Date 28 June 2020

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