Document Type : Systematic reviews


1 Subspecialty Board in Oncology, Hematology and Stem Cell Transplantation, Board Certified Specialist in Internal Medicine, Department of Internal Medicine, Shahid Mostafa Khomeini Hospital, Ilam, Iran

2 Department of Pathology, Ahvaz Jundishapour University of Medical Sciences, Ahvaz, Iran.

3 Nursing Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

4 Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

5 Subspecialist of Pulmonary Diseases, Board Certified and Assistant Professor of Internal Medicine, Department of Internal Medicine, School of Medicine, Shahid Mostafa Khomeini Hospital, Ilam University of Medical Sciences, Ilam. Iran.

6 MD, Pediatric Cardiologist, Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.


Background: Breast cancer is the most common malignancy and a leading cause of death in women. Viruses are known to be the risk factors for breast cancer. The present study aimed to evaluate the association between human papillomavirus (HPV) and the development of breast cancer in Iranian women by a systematic review and meta-analysis.
Methods: The international databases, including Web of Science, Embase, PubMed, Cochrane, and Scopus, were searched in this study. Furthermore, relevant studies published on the association between HPV and breast cancer were identified using the appropriate keywords. The data were analyzed in Stata software (version 14) using the random-effects model.
Results: In total, 18 studies were found eligible to be included in this study. The total sample size was determined at 2466 cases with the mean ages of 47.25 and 39.9 years for experimental and control groups. The overall findings showed a significant relationship between developing breast cancer and HPV infection. The results also revealed that the HPV infection increased the risk of breast cancer in women 5.02 fold more than those without HPV infection (95% CI: 3.46-7.29, I2=65.2%, P=0.003). In addition, the prevalence of HPV infection among women with breast cancer was estimated at 25.66% (95% CI: 17.34-34.95, I2=86%, P=0.000).
Conclusion: HPV infections, especially high-risk HPVs, are significantly frequent in breast cancer samples and should be considered an important risk factor for developing breast cancer.  


  1. Dimri G, Band H, Band V. Mammary epithelial cell transformation: insights from cell culture and mouse models. Breast Cancer Res. 2005;7(4):171-9. doi: 10.1186/bcr1275. [PubMed: 15987472].
  2. 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. [PubMed: 22566779].
  3. 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. Sci Rep. 2017;7:43591. doi: 10.1038/srep43591. [PubMed: 28240743].
  4. Wong M, Pagano JS, Schiller JT, Tevethia SS, Raab-Traub N, Gruber J. New associations of human papillomavirus, Simian virus 40, and Epstein-Barr virus with human cancer. J Natl Cancer Inst. 2002;94(24):1832-6. doi: 10.1093/jnci/94.24.1832. [PubMed: 12488476].
  5. Lawson JS, Salmons B, Glenn WK. Oncogenic viruses and breast cancer: mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma virus (HPV), and epstein–barr virus (EBV). Front Oncol. 2018;8:1. doi: 10.3389/fonc.2018.00001. [PubMed: 29404275].
  6. Boda D, Docea AO, Calina D, Ilie MA, Caruntu C, Zurac S, et al. Human papilloma virus: apprehending the link with carcinogenesis and unveiling new research avenues. Int J Oncol. 2018;52(3):637-55. doi: 10.3892/ijo.2018.4256. [PubMed: 29393378].
  7. Mittal S, Basu P, Muwonge R, Banerjee D, Ghosh I, Sengupta MM, et al. Risk of high‐grade precancerous lesions and invasive cancers in high‐risk HPV‐positive women with normal cervix or CIN 1 at baseline-A population‐based cohort study. Int J Cancer. 2017;140(8):1850-9. doi: 10.1002/ijc.30609. [PubMed: 28108997].
  8. Islam MS, Chakraborty B, Panda CK. Human papilloma virus (HPV) profiles in breast cancer: future management. Ann Transl Med. 2020;8(10):650. doi: 10.21037/atm-19-2756. [PubMed: 32566587].
  9. Hausen HZ. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst. 2000;92(9):690-8. doi: 10.1093/jnci/92.9.690. [PubMed: 10793105].
  10. Liu Y, Klimberg VS, Andrews NR, Hicks CR, Peng H, Chiriva-Internati M, et al. Human papillomavirus DNA is present in a subset of unselected breast cancers. J Hum Virol. 2001;4(6):329-34. [PubMed: 12082399].
  11. Helt AM, Funk JO, Galloway DA. Inactivation of both the retinoblastoma tumor suppressor and p21 by the human papillomavirus type 16 E7 oncoprotein is necessary to inhibit cell cycle arrest in human epithelial cells. J Virol. 2002;76(20):10559-68. doi: 10.1128/jvi.76.20.10559-10568.2002. [PubMed: 12239337].
  12. Degenhardt YY, Silverstein SJ. Gps2, a protein partner for human papillomavirus E6 proteins. J Virol. 2001;75(1):151-60. doi: 10.1128/JVI.75.1.151-160.2001. [PubMed: 11119584].
  13. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1-34. doi: 10.1016/j.jclinepi.2009.06.006. [PubMed: 19631507].
  14. 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):231-7. [PubMed: 27114791].
  15. 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 Pac J Cancer Prev. 2017;18(12):3319-24. doi: 10.22034/APJCP.2017.18.12.3319. [PubMed: 29286226].
  16. Ghaffari H, Nafissi N, Hashemi-Bahremani M, Alebouyeh MR, Tavakoli A, Javanmard D, et al. Molecular prevalence of human papillomavirus infection among Iranian women with breast cancer. Breast Dis. 2018;37(4):207-13. doi: 10.3233/BD-180333. [PubMed: 30124441].
  17. Afshar RM, Balar N, Mollaei HR, Arabzadeh SA, Iranpour M. Low prevalence of human papilloma virus in patients with breast cancer, Kerman; Iran. Asian Pac J Cancer Prev. 2018;19(11):3039-44. doi: 10.31557/APJCP.2018.19.11.3039. [PubMed: 30485938].
  18. Rassi H, Mohammadian T, Salmanpor S, Gholami RE. Retraction: relation between HPV genotypes and BRCA mutation in familial breast cancer. J Microbiol Biotechnol. 2014;8:1407. doi: 10.4014/jmb.1407.07011. [PubMed: 25293631].
  19. Eghbali SS, Amirinejad R, Obeidi N, Mosadeghzadeh S, Vahdat K, Azizi F, et al. Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data. Virol J. 2012;9(1):194. doi: 10.1186/1743-422X-9-194. [PubMed: 22967396].
  20. Jamali ZM, Hamkar R, Ghobadi DV, Delforoush M, Shoja MM, Modares GM. Prevalence of HPV infection and its association with cytological abnormalities of Pap smears in Tehran. Iran J Public Health. 2008;37(3):101-6.
  21. Safaei A, Khanlari M, Momtahen M, Monabati A, Robati M, Amooei S, et al. Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative pap smear in Iran. Indian J Pathol Microbiol. 2010;53(4):681-5. doi: 10.4103/0377-4929.72030. [PubMed: 21045392].
  22. Simões PW, Medeiros LR, Pires PD, Edelweiss MI, Rosa DD, Silva FR, et al. Prevalence of human papillomavirus in breast cancer: a systematic review. Int J Gynecol Cancer. 2012;22(3):343-7. doi: 10.1097/IGC.0b013e31823c712e. [PubMed: 22214962].
  23. Li N, Bi X, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and sporadic breast carcinoma risk: a meta-analysis. Breast Cancer Res Treat. 2011;126(2):515-20. doi: 10.1007/s10549-010-1128-0. [PubMed: 20740311].
  24. Bae JM, Kim EH. Human papillomavirus infection and risk of breast cancer: a meta-analysis of case-control studies. Infect Agents Cancer. 2016;11(1):14. doi: 10.1186/s13027-016-0058-9. [PubMed: 26981149].
  25. Hedau S, Kumar U, Hussain S, Shukla S, Pande S, Jain N, et al. Breast cancer and human papillomavirus infection: no evidence of HPV etiology of breast cancer in Indian women. BMC Cancer. 2011;11(1):27. doi: 10.1186/1471-2407-11-27. [PubMed: 21247504].
  26. 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. [PubMed: 27797244].
  27. 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. [PubMed: 24935597].
  28. Khodabandehlou N, Mostafaei S, Etemadi A, Ghasemi A, Payandeh M, Hadifar S, et al. Human papilloma virus and breast cancer: the role of inflammation and viral expressed proteins. BMC Cancer. 2019;19(1):61. doi: 10.1186/s12885-019-5286-0. [PubMed: 30642295].
  29. Seyedi 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. Iran J Obstet Gynecol Infertil. 2009;12(2):1-4.
  30. Aghdam MK, Nadji SA, Alvandimanesh A, Maliheh M, Khademi Y. Absence of human papillomavirus in benign and malignant breast tissue. Iran J Pathol. 2019;14(4):279-83. doi: 10.30699/ijp.2019.89684.1847. [PubMed: 31754356].
  31. Manzouri L, Salehi R, Shariatpanahi S, Rezaie P. Prevalence of human papilloma virus among women with breast cancer since 2005-2009 in Isfahan. Adv Biomed Res. 2014;3:75. doi: 10.4103/2277-9175.125873. [PubMed: 24627883].
  32. 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):41-6. [PubMed: 26516324].
  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. doi: 10.22034/apjcp.2016.17.10.4741. [PubMed: 27893206].
  34. Tahmasebi Fard Z, Abdirad A, Saatian M, Arefian L. Association between human Papillomavirus (HPV) and breast cancer in Iranian patients. Med Sci J Islam Azad Univ Tehran Med Branch. 2013;23(2):120-6.
  35. Hossein R, Behzad S, Tahar M, Azadeh NA. Prevalence of human papillomavirus genotypes associated with cervical and breast cancers in Iran. Monoclon Antib Immunodiagn Immunother. 2013;32(6):399-403. doi: 10.1089/mab.2013.0047. [PubMed: 24328743].
  36. Mohtasebi P, Rassi H, Maleki F, Hajimohammadi S, Bagheri Z, Fakhar miandoab M, et al. Detection of human papillomavirus genotypes and major BRCA mutations in familial breast cancer. Monoclon Antib Immunodiagn Immunother. 2016;35(3):135-40. doi: 10.1089/mab.2015.0081. [PubMed: 27186947].
  37. Rezaei H, Rassi H, Mansur FN. Investigation of Methylenetetrahydrofolate reductase C677T polymorphism and human papilloma virus genotypes in Iranian breast cancer. Monoclon Antib Immunodiagn Immunother. 2017;36(3):124-8. doi: 10.1089/mab.2017.0011. [PubMed: 28537481].
  38. 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. [PubMed: 21276129].
  39. Salehpour M, Meibodi NT, 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. [PubMed: 26351484].