Skip to main content

Advertisement

SpringerLink
Log in

The role of human papillomavirus infection in breast cancer

  • Review Article
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Breast cancer is the leading female cancer and the third most common cause of cancer deaths worldwide. Many studies have suggested a possible link between breast cancer pathogenesis and viral infection, particularly mouse mammary tumour virus, simian virus 40, Epstein–Barr virus, and human papillomavirus (HPV). A significant number of recent studies have reported that approximately 29% of human breast cancer tissues were positive for high-risk HPV subtypes, especially HPV subtypes 16, 18, or 33. In contrast, several other investigations did not detect any HPV subtypes in either breast cancer tissue or normal breast tissue from patients diagnosed with breast cancer. Given these conflicting data and the established complexity of the association between HPV with other cancers, a definitive relationship between human breast cancer and HPV infection has not been determined. Recent advances in laboratory methodologies aim to overcome the inherent challenges in detecting HPV in breast cancer tissue. There is an urgent need to obtain additional evidence in order to assess the possibility of breast cancer prevention using HPV vaccines.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Amarante MK, Watanabe MA. The possible involvement of virus in breast cancer. J Cancer Res Clin Oncol. 2009;135:329–37.

    Article  PubMed  Google Scholar 

  2. Anders CK, Carey LA. Biology, metastatic patterns, and treatment of patients with triple-negative breast cancer. Clin Breast Cancer. 2009;9:S73–81.

    Article  PubMed  CAS  Google Scholar 

  3. Joshi D, Quadri M, Gangane N, et al. Association of Epstein Barr virus infection (EBV) with breast cancer in rural Indian women. PLoS One. 2009;4:e8180.

    Article  PubMed  Google Scholar 

  4. Altundag K, Baptista MZ. Human papilloma virus and breast cancer. Br J Cancer. 2006;94:338. author reply 339.

    Article  PubMed  CAS  Google Scholar 

  5. Melana SM, Nepomnaschy I, Hasa J, et al. Detection of human mammary tumour virus proteins in human breast cancer cells. J Virol Methods. 2010;163:157–61.

    Article  PubMed  CAS  Google Scholar 

  6. Sifuentes Alvarez A, Reyes Romero M. Risk factors for cervico-uterine cancer associated to HPV: p53 codon 72 polymorphism in women attending hospital care. Ginecol Obstet Mex. 2003;71:12–5.

    PubMed  CAS  Google Scholar 

  7. Hausen HZ. Papillomaviruses–to vaccination and beyond. Biochemistry (Mosc). 2008;73:498–503.

    Article  Google Scholar 

  8. Gentschev I, Stritzker J, Hofmann E, et al. Use of an oncolytic vaccinia virus for the treatment of canine breast cancer in nude mice: preclinical development of a therapeutic agent. Cancer Gene Ther. 2009;16:320–8.

    Article  PubMed  CAS  Google Scholar 

  9. Buonaguro FM, Tornesello ML, Buonaguro L. Virus-like particle vaccines and adjuvants: the HPV paradigm. Expert Rev Vaccines. 2009;8:1379–98.

    Article  PubMed  CAS  Google Scholar 

  10. Munger K, Baldwin A, Edwards KM, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol. 2004;78:11451–60.

    Article  PubMed  Google Scholar 

  11. Holly EA. Cervical intraepithelial neoplasia, cervical cancer, and HPV. Annu Rev Public Health. 1996;17:69–84.

    Article  PubMed  CAS  Google Scholar 

  12. Pizzighella S, Rassu M, Piacentini I, et al. Polymerase chain reaction amplification and restriction enzyme typing as an accurate and simple way to detect and identify human papillomaviruses. J Med Microbiol. 1993;39:33–8.

    Article  PubMed  CAS  Google Scholar 

  13. Yang L, Mohr I, Fouts E, et al. The E1 protein of bovine papilloma virus 1 is an ATP-dependent DNA helicase. Proc Natl Acad Sci U S A. 1993;90:5086–90.

    Article  PubMed  CAS  Google Scholar 

  14. Rintala MA, Grenman SE, Puranen MH, et al. Transmission of high-risk human papillomavirus (HPV) between parents and infant: a prospective study of HPV in families in Finland. J Clin Microbiol. 2005;43:376–81.

    Article  PubMed  Google Scholar 

  15. DiMaio D, Mattoon D. Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene. 2001;20:7866–73.

    Article  PubMed  CAS  Google Scholar 

  16. Howley PM, Munger K, Werness BA, et al. Molecular mechanisms of transformation by the human papillomaviruses. Princess Takamatsu Symp. 1989;20:199–206.

    PubMed  CAS  Google Scholar 

  17. Scheffner M, Huibregtse JM, Vierstra RD, et al. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993;75:495–505.

    Article  PubMed  CAS  Google Scholar 

  18. Dyson N, Howley PM, Munger K, et al. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989;243:934–7.

    Article  PubMed  CAS  Google Scholar 

  19. Dyson N, Guida P, Munger K, et al. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J Virol. 1992;66:6893–902.

    PubMed  CAS  Google Scholar 

  20. Stubenrauch F, Laimins LA. Human papillomavirus life cycle: active and latent phases. Semin Cancer Biol. 1999;9:379–86.

    Article  PubMed  CAS  Google Scholar 

  21. Centers for Disease Control and Prevention. Human papillomavirus: HPV information for clinicians. Ala Nurse. 2008;35:17–9.

    Google Scholar 

  22. zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer. 2002;2:342–50.

    Article  PubMed  CAS  Google Scholar 

  23. Clifford GM, Smith JS, Aguado T, et al. Comparison of HPV type distribution in high-grade cervical lesions and cervical cancer: a meta-analysis. Br J Cancer. 2003;89:101–5.

    Article  PubMed  CAS  Google Scholar 

  24. Nemes JA, Deli L, Nemes Z, et al. Expression of p16(INK4A), p53, and Rb proteins are independent from the presence of human papillomavirus genes in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:344–52.

    Article  PubMed  Google Scholar 

  25. Crum CP, McLachlin CM, Tate JE, et al. Pathobiology of vulvar squamous neoplasia. Curr Opin Obstet Gynecol. 1997;9:63–9.

    PubMed  CAS  Google Scholar 

  26. Klencke BJ, Palefsky JM. Anal cancer: an HIV-associated cancer. Hematol Oncol Clin North Am. 2003;17:859–72.

    Article  PubMed  Google Scholar 

  27. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 1995;64:1–378.

  28. Teitelman AM, Stringer M, Averbuch T, et al. Human papillomavirus, current vaccines, and cervical cancer prevention. J Obstet Gynecol Neonatal Nurs. 2009;38:69–80.

    Article  PubMed  Google Scholar 

  29. Rylander E, Ruusuvaara L, Almstromer MW, et al. The absence of vaginal human papillomavirus 16 DNA in women who have not experienced sexual intercourse. Obstet Gynecol. 1994;83:735–7.

    PubMed  CAS  Google Scholar 

  30. Sawaya GF, Smith-McCune K. HPV vaccination–more answers, more questions. N Engl J Med. 2007;356:1991–3.

    Article  PubMed  CAS  Google Scholar 

  31. Revzina NV, Diclemente RJ. Prevalence and incidence of human papillomavirus infection in women in the USA: a systematic review. Int J STD AIDS. 2005;16:528–37.

    Article  PubMed  CAS  Google Scholar 

  32. Baldwin P, Laskey R, Coleman N. Translational approaches to improving cervical screening. Nat Rev Cancer. 2003;3:217–26.

    Article  PubMed  CAS  Google Scholar 

  33. Winer RL, Lee SK, Hughes JP, et al. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218–26.

    Article  PubMed  Google Scholar 

  34. Lipskie TL. A summary of cancer screening guidelines. Chronic Dis Can. 1998;19:112–30.

    PubMed  CAS  Google Scholar 

  35. Rambout L, Hopkins L, Hutton B, et al. Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials. CMAJ. 2007;177:469–79.

    Article  PubMed  Google Scholar 

  36. de León DC, Montiel DP, Nemcova J, et al. Human papillomavirus (HPV) in breast tumours: prevalence in a group of Mexican patients. BMC Cancer. 2009;9:26.

    Article  PubMed  Google Scholar 

  37. Di Lonardo A, Venuti A, Marcante ML. Human papillomavirus in breast cancer. Breast Cancer Res Treat. 1992;21:95–100.

    Article  PubMed  CAS  Google Scholar 

  38. Hennig EM, Suo Z, Thoresen S, et al. Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). Breast Cancer Res Treat. 1999;53:121–35.

    Article  PubMed  CAS  Google Scholar 

  39. Hennig EM, Kvinnsland S, Holm R, et al. Significant difference in p53 and p21 protein immunoreactivity in HPV 16 positive and HPV negative breast carcinomas. Acta Oncol. 1999;38:931–8.

    Article  PubMed  CAS  Google Scholar 

  40. Yu Y, Morimoto T, Sasa M, et al. Human papillomavirus type 33 DNA in breast cancer in Chinese. Breast Cancer. 2000;7:33–6.

    Article  PubMed  CAS  Google Scholar 

  41. Liu Y, Klimberg VS, Andrews NR, et al. Human papillomavirus DNA is present in a subset of unselected breast cancers. J Hum Virol. 2001;4:329–34.

    PubMed  CAS  Google Scholar 

  42. Damin AP, Karam R, Zettler CG, et al. Evidence for an association of human papillomavirus and breast carcinomas. Breast Cancer Res Treat. 2004;84:131–7.

    Article  PubMed  CAS  Google Scholar 

  43. Widschwendter A, Brunhuber T, Wiedemair A, et al. Detection of human papillomavirus DNA in breast cancer of patients with cervical cancer history. J Clin Virol. 2004;31:292–7.

    Article  PubMed  CAS  Google Scholar 

  44. de Villiers EM, Sandstrom RE, zur Hausen H, et al. Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast. Breast Cancer Res. 2005;7:R1–11.

    Article  PubMed  Google Scholar 

  45. Kan CY, Iacopetta BJ, Lawson JS, et al. Identification of human papillomavirus DNA gene sequences in human breast cancer. Br J Cancer. 2005;93:946–8.

    Article  PubMed  CAS  Google Scholar 

  46. Kroupis C, Markou A, Vourlidis N, et al. Presence of high-risk human papillomavirus sequences in breast cancer tissues and association with histopathological characteristics. Clin Biochem. 2006;39:727–31.

    Article  PubMed  CAS  Google Scholar 

  47. Gumus M, Yumuk PF, Salepci T, et al. HPV DNA frequency and subset analysis in human breast cancer patients’ normal and tumoural tissue samples. J Exp Clin Cancer Res. 2006;25:515–21.

    PubMed  CAS  Google Scholar 

  48. Damin AP, Damin DC, Alexandre CO. HPV infection and breast cancer. Breast. 2007;16:222.

    Article  PubMed  CAS  Google Scholar 

  49. Yasmeen A, Bismar TA, Kandouz M, et al. E6/E7 of HPV type 16 promotes cell invasion and metastasis of human breast cancer cells. Cell Cycle. 2007;6:2038–42.

    Article  PubMed  CAS  Google Scholar 

  50. Kulka J, Kovalszky I, Svastics E, et al. Lymphoepithelioma-like carcinoma of the breast: not Epstein-Barr virus-, but human papilloma virus-positive. Hum Pathol. 2008;39:298–301.

    Article  PubMed  CAS  Google Scholar 

  51. Sarkola M, Rintala M, Grenman S, et al. Human papillomavirus DNA detected in breast milk. Pediatr Infect Dis J. 2008;27:557–8.

    Article  PubMed  Google Scholar 

  52. Akil N, Yasmeen A, Kassab A, et al. 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;99:404–7.

    Article  PubMed  CAS  Google Scholar 

  53. Heng B, Glenn WK, Ye Y, et al. Human papilloma virus is associated with breast cancer. Br J Cancer. 2009;101:1345–50.

    Article  PubMed  CAS  Google Scholar 

  54. Bratthauer GL, Tavassoli FA, O’Leary TJ. Etiology of breast carcinoma: no apparent role for papillomavirus types 6/11/16/18. Pathol Res Pract. 1992;188:384–6.

    Article  PubMed  CAS  Google Scholar 

  55. Wrede D, Luqmani YA, Coombes RC, et al. Absence of HPV 16 and 18 DNA in breast cancer. Br J Cancer. 1992;65:891–4.

    Article  PubMed  CAS  Google Scholar 

  56. Gopalkrishna V, Singh UR, Sodhani P, et al. Absence of human papillomavirus DNA in breast cancer as revealed by polymerase chain reaction. Breast Cancer Res Treat. 1996;39:197–202.

    Article  PubMed  CAS  Google Scholar 

  57. Lindel K, Forster A, Altermatt HJ, et al. Breast cancer and human papillomavirus (HPV) infection: no evidence of a viral etiology in a group of Swiss women. Breast. 2007;16:172–7.

    Article  PubMed  Google Scholar 

  58. de Cremoux P, Thioux M, Lebigot I, et al. No evidence of human papillomavirus DNA sequences in invasive breast carcinoma. Breast Cancer Res Treat. 2008;109:55–8.

    Article  PubMed  CAS  Google Scholar 

  59. Khan NA, Castillo A, Koriyama C, et al. Human papillomavirus detected in female breast carcinomas in Japan. Br J Cancer. 2008;99:408–14.

    Article  PubMed  CAS  Google Scholar 

  60. Mendizabal-Ruiz AP, Morales JA, Ramirez-Jirano LJ, et al. Low frequency of human papillomavirus DNA in breast cancer tissue. Breast Cancer Res Treat. 2009;114:189–94.

    Article  PubMed  CAS  Google Scholar 

  61. Choi YL, Cho EY, Kim JH, et al. Detection of human papillomavirus DNA by DNA chip in breast carcinomas of Korean women. Tumour Biol. 2007;28:327–32.

    Article  PubMed  CAS  Google Scholar 

  62. Branca M, Ciotti M, Giorgi C, et al. Up-regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high-risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer. Eur J Obstet Gynecol Reprod Biol. 2007;130:223–31.

    Article  PubMed  CAS  Google Scholar 

  63. zur Hausen H. Human papillomavirus & cervical cancer. Indian J Med Res. 2009;130:209.

    PubMed  Google Scholar 

  64. Vonka V. Causality in medicine: the case of tumours and viruses. Philos Trans R Soc Lond B Biol Sci. 2000;355:1831–41.

    Article  PubMed  CAS  Google Scholar 

  65. Lawson JS. Do viruses cause breast cancer? Methods Mol Biol. 2009;471:421–38.

    Article  PubMed  Google Scholar 

  66. Liang W, Tian H. Hypothetic association between human papillomavirus infection and breast carcinoma. Med Hypotheses. 2008;70:305–7.

    Article  PubMed  Google Scholar 

  67. Anhang R, Goodman A, Goldie SJ. HPV communication.review of existing research and recommendations for patient education. CA Cancer J Clin. 2004;54:248–59.

    Article  PubMed  Google Scholar 

  68. zur Hausen H. The search for infectious causes of human cancers: where and why (Nobel lecture). Angew Chem Int Ed Engl. 2009;48:5798–808.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research is funded by National Natural Science Foundation of China (Grant No. 30872514 and 30600597).

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, No. 127, Changle West Road, 710032, Xi’an, Shaanxi Province, China

    Ting Wang, Peng Chang, Ling Wang, Qing Yao, Wen Guo & Jianghao Chen

  2. Department of Cardiothoracic Surgery, The Baird Institute for Applied Heart and Lung Surgical Research and The Royal Prince Alfred Hospital, Sydney, NSW, Australia

    Tristan Yan & Christopher Cao

Authors
  1. Ting Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ling Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Qing Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wen Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianghao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tristan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Christopher Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ling Wang or Jianghao Chen.

Additional information

T. Wang and P. Chang contributed equally to this article.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, T., Chang, P., Wang, L. et al. The role of human papillomavirus infection in breast cancer. Med Oncol 29, 48–55 (2012). https://doi.org/10.1007/s12032-010-9812-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9812-9

Keywords

Search

Navigation