Document Type: Original Research


1 Pediatric Pathology Research Center, Research Institute for Children’s Heath, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Virology Research Center (VRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Department of Pathology, Shafa Hospital, Qazvin University of Medical Sciences, Qazvin, Iran

5 Department of Pathology, Pathobiology Laboratory Center, Tehran, Iran



Background & Objective: Malignant breast tumors, which are one of the most important deadly cancers in women, like many other cancers, are proposed to be related to viruses etiologically. Proper management of breast carcinoma necessitates an identification of the etiological factors. Human Papillomavirus is considered to have an etiological role in breast carcinoma. We carried out this study to find out if Human Papillomavirus-DNA is present in the malignant and benign breast tissue in our patients.
Methods: Seventy five paraffin-embedded breast cancer tissues and 75 normal breast tissues and benign breast lesions were examined in this study (case-control) to look for Human Papillomavirus-DNA employing Nested Polymerase Chain reaction. The tissues were examined over a period of ten years in the pathology department of the Pathobiology Laboratory Center of Tehran.
Results: No Human Papillomavirus-DNA was found in any of the malignant or control group specimens.
Conclusion: Our results showed no evidence of Human Papillomavirus in cancerous and benign tissues, which is consistent with some other studies in English medical literature. More investigations using more specimens from different parts of the country are required to confirm the presence or absence of any connection between Human Papillomavirus and development of breast carcinoma in Iran.


Main Subjects

  1. Cohen JI. Epstein-Barr virus vaccines. Clinical & translational immunology. 2015;4(1):e32. [DOI:10.1038/ cti.2014.27] [PMID] [PMCID]
  2. Smith E. Can we wipe out cancers caused by the Epstein-Barr Virus? Bio Med Central. Dec 2015 (The Open Access Publisher). Available from: URL: https://blogs.biome /can-wipe-cancers-caused-epstein-barr-virus/
  3. Tsai JH, Tsai CH, Cheng MH, Lin SJ, Xu FL, Yang CC. Association of viral factors with non‐familial breast cancer in Taiwan by comparison with non‐cancerous, fibroadenoma, and thyroid tumor tissues. J Med Virol. 2005;75(2):276-81. [DOI:10.1002/jmv.20267] [PMID]
  4. Hsu CR, Lu TM, Chin LW, Yang CC. Possible DNA viral factors of human breast cancer. Cancers (Basel). 2010;2(2):498-512. [DOI:10.3390/cancers2020498] [PMID] [PMCID]
  5. 5. Khoddami M, Nadji SR, Dehghanian P, Vahdatinia M, Shamshiri AR. Detection of Epstein-Barr virus DNA in langerhans cell histiocytosis. Jundishapur J Microbio. 2015;8(12):e27219. [DOI:10.5812/jjm.27219] [PMID] [PMCID]
  6. Salman NA, Davies G, Majidy F, Shakir F, Akinrinade H, Perumal D, et al. Association of high-risk human papillomavirus and breast cancer: a UK based study. Scientific Reports. 2017;7. [DOI:10.1038/srep43591] [PMID] [PMCID]
  7. Ashrafi GH, Haghshenas MR, Marchetti B, O'Brien PM, Campo MS. E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I. Int J Cancer. 2005;113(2):276-83. [DOI:10.1002/ijc.20558] [PMID]
  8. Lawson JS, Günzburg WH, Whitaker NJ. Viruses and human breast cancer. Future Microbiol. 2006;1(1):33-51. [DOI:10.2217/17460913.1.1.33] [PMID]
  9. Islam S, Dasgupta H, Roychowdhury A, Bhattacharya R, Mukherjee N, Roy A, et al. Study of association and molecular analysis of human papillomavirus in breast cancer of Indian patients: Clinical and prognostic implication. PloS one. 2017;12(2):e0172760. [DOI:10.1371/journal .pone.0172760] [PMID] [PMCID]
  10. Saiki RK, Bugawan TL, Horn GT, Mullis KB, Erlich HA. Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes. Nature. 1986;324(6093):163. [DOI:10.1038/324163a0] [PMID]
  11. Sotlar K, Diemer D, Dethleffs A, Hack Y, Stubner A, Vollmer N,et al. Detection and typing of human papillomavirus by e6 nested multiplex PCR. J Clin Microbiol. 2004;42(7):3176-84. [DOI:10.1128/JCM.42 .7.3176-3184.2004] [PMID] [PMCID]
  12. Haghshenas MR, Mousavi T, Moosazadeh M, Afshari M. Human papillomavirus and breast cancer in Iran: a meta-analysis. Iran J Basic Med Sci. 2016;19(3):231.
  13. Lawson JS, Glenn WK, Whitaker NJ. Human Papilloma Viruses and Breast Cancer-Assessment of Causality. Front Oncol. 2016;6:207. [DOI:10.3389/fonc.2016.00207] [PMID] [PMCID]
  14. Lindel K, Forster A, Altermatt HJ, Greiner R, Gruber G. Breast cancer and human papillomavirus (HPV) infection: no evidence of a viral etiology in a group of Swiss women. Breast. 2007;16(2):172-7. [DOI:10.1016/j.breast.2006. 09.001] [PMID]
  15. Joshi D, Buehring GC. Are viruses associated with human breast cancer? Scrutinizing the molecular evidence. Breast Cancer Res Treat. 2012;135(1):1-15. [DOI:10.1007/s10549-011-1921-4] [PMID]
  16. Liang W, Wang J, Wang C, Lv Y, Gao H, Zhang K, et al. Detection of high‐risk human papillomaviruses in fresh breast cancer samples using the hybrid capture 2 assay. J Med Virol. 2013;85(12):2087-92. [DOI:10.1002/ jmv.23703] [PMID]
  17. Herrera-Romano L, Fernández-Tamayo N, Gómez-Conde E, Reyes-Cardoso JM, Ortiz-Gutierrez F, Ceballos Gm, et al. Absence of human papillomavirus sequences in epithelial breast cancer in a Mexican female population. Med Oncol. 2012;29(3):1515-7. [DOI:10.1007/s12032-011-0059-x] [PMID]
  18. Choi J, Kim C, Lee HS, Choi YJ, Kim HY, Lee J, et al. Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer. J Pathol Transl Med. 2016;50(6):442-50. [DOI:10.4132/jptm.2016.07.08] [PMID] [PMCID]
  19. Antonsson A, Spurr TP, Chen AC, Francis GD, McMillan NA, Saunders NA, et al. High prevalence of human papillomaviruses in fresh frozen breast cancer samples. J Med Virol. 2011;83(12):2157-63.[DOI:10.1002/jmv.22223] [PMID]
  20. Glenn WK, Heng B, Delprado W, Iacopetta B, Whitaker NJ, Lawson JS. Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer. PloS one. 2012;7(11):e48788. [DOI:10.1371/ journal.pone.0048788] [PMID] [PMCID]
  21. Suarez ALP, Lorenzetti MA, Lucano RG, Cohen M, Gass H, Vazquez P M, et al. Presence of human papilloma virus in a series of breast carcinoma from Argentina. PLoS One. 2013;8(4):e61613. [DOI:10.1371/journal.pone.0061613] [PMID] [PMCID]
  22. Bae JM, Kim EH. Human papillomavirus infection and risk of breast cancer: a meta-analysis of case-control studies. Infect agent cancer. 2016;11(1):14. [DOI:10.1186/s13027-016-0058-9] [PMID] [PMCID]
  23. Sigaroodi A, Nadji SA, Naghshvar F, Nategh R, Emami H, Velayati AA. Human papillomavirus is associated with breast cancer in the north part of Iran. Sci World J. 2012;2012:837191. [DOI:10.1100/2012/837191] [PMID] [PMCID]
  24. Alavi G, Sharifi N, Sadeghian A, Jabari H, Bahreyni M, Bagheri H. Presence of human papilloma virus sequences in breast cancer tissues and association with histopathological features. IJOGI. 2009;12(2):1-4.
  25. Ghaffari SR, Sabokbar T, Meshkat Z, Fereidooni F, Dastan J, Rafati M, et al. Tracing human papilloma virus in breast tumors of Iranian breast cancer patients. Breast J. 2011;17(2):218-9. [DOI:10.1111/j.1524-4741.2010.01053.x] [PMID]
  26. Rassi H, Salehi B, Mohammadian T, Nahavandi Araghi A. Prevalence of human papillomavirus genotypes associated with cervical and breast cancers in Iran. Monoclon Antib Immunodiagn Immunother. 2013 Dec;32(6):399-403. [DOI:10.1089/mab.2013.0047] [PMID]
  27. Manzouri L, Salehi R, Shariatpanahi S. Prevalence of human papilloma virus among women with breast cancer since 2005-2009 in Isfahan. Adv Biomed Res. 2014;3(1):75-80. [DOI:10.4103/2277-9175.125873] [PMID] [PMCID]
  28. Eslamifar A, Ramezani A, Azadmanesh K, Bidari-Zerehpoosh F, Banifazl M, Aghakhani A. Assessment of the association between human papillomavirus infection and breast carcinoma. Iran J Pathol. 2015;10(1):41.
  29. Ahangar-Oskouee M, Shahmahmoodi S, Jalilvand S, Mahmoodi M, Ziaee AA, Esmaeili HA, et al. No detection of 'high-risk'human papillomaviruses in a group of Iranian women with breast cancer. Asian Pac J Cancer Prev. 2014;15(15):4061-5. [DOI:10.7314/APJCP.2014.15.9.4061] [PMID]
  30. Moradi A, Mobasheri E, Tabarraei A, Bakhshandeh Nosrat S, Azarhosh R, Alizadeh S, et al. Molecular epidemiology of Human Papillomaviruses in breast cancer, Golestan province of Iran. Med Lab J. 2009;3(1).
  31. Tahmasebi Fard Z. The relationship between Human Papillomavirus and Epstein-Barr virus infections with breast cancer of Iranian patients. Res Mol Med. 2013;1(3):38-42. [DOI:10.18869/acadpub.rmm.1.3.38]
  32. Doosti M, Bakhshesh M, Zahir ST, Shayestehpour M, Karimi-Zarchi M. Lack of Evidence for a Relationship between High-Risk Human Papillomaviruses and Breast Cancer in Iranian Patients. Asian Pac J Cancer Prev. 2016;17(9):4357-61.
  33. Karimi M, Khodabandehloo M, Nikkhoo B, Ghaderi E. No Significant Association between Human Papillomavirus and Breast Cancer, Sanandaj, Iran. Asian Pac J Cancer Prev. 2016;17(10):4741-5.
  34. Salehpour M, Tayyebi Meibodi N, Teimourpour R, Ghorani-Azam A, Sepahi S, Rostami S, et al. Frequency of Human Papillomavirus Genotypes 6, 11, 16, 18 And 31 in Paraffin-Embedded Tissue Samples of Invasive Breast Carcinoma, North-East of Iran. Iran J Pathol. 2015;10(3):192-8.