Human papillomavirus and breast cancer in Iran: a meta- analysis

Document Type : Review Article


1 Department of Microbiology, Molecular and Cell-Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2 Student Research Committee, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Health Sciences Research Center, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Community Medicine, Zabol University of Medical Sciences, Zabol, Iran


Objective(s):This study aims to investigate the relationship between human papillomavirus (HPV) and breast cancer using meta- analysis.
Materials and Methods: Relevant studies were identified reviewing the national and international databases. We also increased the search sensitivity by investigating the references as well as interview with research centers and experts. Finally, quality assessment and implementation of inclusion/exclusion criteria determined the eligible articles for meta-analysis. Based on the heterogeneity observed among the results of the primary studies, random effects model was used to estimate the pooled prevalence of HPV infection and also pooled odds ratio between HPV and developing breast cancer using Stata SE V. 11 software.
Results:This meta- analysis included 11 primary studies investigating the HPV infection prevalence among 1539 Iranian women. Pooled prevalence (95% confidence interval) of HPV infection among Iranian women with breast cancer was estimated as of 23.6% (6.7- 40.5), while, the odds ratio               (95% confidence interval) between HPV infection and developing breast cancer was estimated as of 5.7% (0.7- 46.8).
Conclusion: This meta- analysis showed a high prevalence of HPV infection among women with breast cancer. We also found that the odds of developing breast cancer among women with breast cancer was more than that of women without breast cancer.


1. Haghshenas M, Golini-Moghaddam T, Rafiei A, Emadeian O, Shykhpour A, Ashrafi GH. Prevalence and type distribution of high- risk human papilloma-virus in patients with cervical cancer: a population-based study. Infect Agent Cancer 2013; 8:20.
2. Wang T, Zeng X, Li W, Zhu H, Wang G, Liu X, et al. Detection and analysis of human papillomavirus (HPV) DNA in breast cancer patients by an effective method of HPV capture. PloS one 2014; 9:e90343.
3. Simões PW, Medeiros LR, Pires PDS, Edelweiss MI, Rosa DD, Silva FR, et al. Prevalence of human papillomavirus in breast cancer: a systematic review. Int J Gynecol Cancer  2012; 22:343-347.
4.Lawson JS, Heng B. Viruses and breast cancer. Cancers (Basel) 2010; 2:752-772.
5.Ashrafi GH, Haghshenas MR, Marchetti B, O'Brien PM, Campo MS. E5 protein of human papillomavirus type 16 selectively down regulates surface HLA class I. Int J Cancer 2005; 113:276-283.
6.Mou X, Chen L, Liu F, Shen Y, Wang H, Li Y, et al. Low prevalence of human papillomavirus (HPV) in Chinese patients with breast cancer. J Int Med Res 2011; 39:1636-1644.
7.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; 11:27-37.
8.Tahmasebi Fard Z, Abdirad A, Saatian M, Arefian L. Association between human Papillomavirus (HPV) and breast cancer in Iranian patients. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch 2013; 23:120-126.
9.Moradi A, Mobasheri E, Tabarraei A, Bakhshandeh Nosrat S, Azarhosh R, Alizadeh S, et al. Molecular epidemiology of human Papillomavirus in breast cancer, Golestan province of Iran. Medical Laboratory Journal 2009; 3:9-14.
10. Hsu CR, Lu TM, Chin LW, Yang CC. Possible DNA viral factors of human breast cancer. Cancers (Basel) 2010; 2:498-512. León DC, Montiel DP, Nemcova J, Mykyskova I, Turcios E, Villavicencio V, et al. Human papillomavirus (HPV) in breast tumors: prevalence in a group of Mexican patients. BMC cancer 2009; 9:26-31.
12.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 2014; 10:41-46.
13.Ahangar-Oskouee M, Shahmahmoodi S, Jalilvand S, Mahmoodi M, Ziaee AA, Esmaeili HA, et al. No detection of 'high-risk' human papillomavirus in a group of Iranian women with breast cancer. Asian Pac J Cancer Prev 2014; 15:4061-4065.
14.Moosazadeh M. Meta-analysis of prevalence of smoking in 15-64-year-old population of west of Iran. Int J Prev Med 2013; 4:1108-1114.
15.Moosazadeh M, Ziaaddini H, Mirzazadeh A, Ashrafi-Asgarabad A, Haghdoost AA. Meta-analysis of smoking prevalence in Iran. Addiction & health 2013; 5:140-153.
16.Moosazadeh M, Nekoei‐moghadam M, Emrani Z, Amiresmaili M. Prevalence of unwanted pregnancy in Iran: a systematic review and meta‐analysis. Int J Health Plann Manage 2014; 29:e277-e90.
17.Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology [STROBE] statement: guidelines for reporting observational studies. Gaceta Sanitaria 2008;22:144-150.
18.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; 32:399-403.
19.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. The breast journal 2011; 17:218-219.
20.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: 192-198.
21.Rassi H, Mohammadian T, Salmanpor S, Roudmajani EG. Relation between HPV genotypes and BRCA mutation in familial breast cancer. J Microbiol Biotechnol. 2014.
22.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. Scientific World Journal 2012; 2012: :837191.
23.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: 75-80.
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;12:1-4.
25.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; 126:515-520.
26.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; 9:194-199.
27. Zavarei MJZJ, Hamkar R, Dana VG, Delforoosh M, Shojamoradi M, Gilani MM. Prevalence of HPV infection and its association with cytological abnormalities of Pap smears in Tehran. Iran J Public Health 2008; 37:101-106.
28.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; 53:681-685.
29.Zandi K, Eghbali SS, Hamkar R, Ahmadi S, Ramedani E, Deilami I, et al. Prevalence of various human Papillomavirus (HPV) genotypes among women who subjected to routine Pap smear test in Bushehr city (South west of Iran) 2008-2009. Virol J. 2010; 22:65-69.
30.Silva Jr RG, Da Silva BB. No evidence for an association of human papillomavirus and breast carcinoma. Breast Cancer Res Treat 2011; 125:261-264. Cremoux P, Thioux M, Lebigot I, Sigal-Zafrani B, Salmon R, Sastre-Garau X. No evidence of human papillomavirus DNA sequences in invasive breast carcinoma. Breast Cancer Res Treat 2008; 109:55-58.
32.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;16:172-177.
33.Wrede D, Luqmani Y, Coombes R, Vousden K. Absence of HPV 16 and 18 DNA in breast cancer. Br J Cancer 1992; 65:891-894.
34.Mendizabal-Ruiz A, Morales J, Ramirez-Jirano L, Padilla-Rosas M, Morán-Moguel M, Montoya-Fuentes H. Low frequency of human papillomavirus DNA in breast cancer tissue. Breast Cancer Res Treat 2009; 114:189-194.
35.Kroupis C, Markou A, Vourlidis N, Dionyssiou-Asteriou A, Lianidou ES. Presence of high-risk human papillomavirus sequences in breast cancer tissues and association with histopathological characteristics. Clinical biochemistry 2006; 39:727-231.
36.Lawson J, Glenn W, Heng B, Ye Y, Tran B, Lutze-Mann L, et al. Koilocytes indicate a role for human papilloma virus in breast cancer. Br J Cancer 2009; 101:1351-1356.
37.Akil N, Yasmeen A, Kassab A, Ghabreau L, Darnel A, Al Moustafa A. High-risk human papillomavirus infections in breast cancer in Syrian women and their association with Id-1 expression: a tissue microarray study. Br J Cancer 2008; 99:404-407.
38.Gumus M, Yumuk P, Salepci T, Aliustaoglu M, Dane F, Ekenel M, et al. HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples. J Exp Clin Cancer Res 2006; 25:515-521.
39.Ali S, Al-Alwan N, Al-Alwany S. Detection and genotyping of human papillomavirus in breast cancer tissues from Iraqi patients. East Mediterr Health J 2014; 20: 372-376. Villiers E-M, Sandstrom RE, zur Hausen H, Buck CE. Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast. Breast Cancer Res 2005; 7:R1-11.
41.Fakhraei F, Haghshenas MR. Human Papillomavirus and Cancer. J Mazand Univ Med Sci. 2013; 23:340-360.
42.Frega A, Lorenzon L, Bononi M, De Cesare A, Ciardi A, Lombardi D, et al. Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer. Eur J Gynaecol Oncol 2011; 33: 164-167.