Breast cancer and human papillomavirus (HPV) infection: No evidence of a viral etiology in a group of Swiss women

doi:10.1016/j.breast.2006.09.001

The Breast

Volume 16, Issue 2, April 2007, Pages 172-177

https://doi.org/10.1016/j.breast.2006.09.001 Get rights and content

Summary

There are controversial data on the meaning of viral induction of breast cancer. The aim of this study was to investigate the presence of human papillomavirus (HPV) DNA in patients with breast carcinoma and the correlation of viral infection with disease outcome. Paraffin-embedded sections from 81 patients with breast cancer were analyzed for HPV DNA by polymerase chain reaction (PCR) using the SPF1/2 primers covering about 40 different low-, intermediate- and high-risk types. We found all samples were negative for HPV DNA. Our analysis could not support a role of HPV in breast carcinoma. Controversial published data indicate a need for further, larger epidemiologic studies.

Introduction

Human papillomaviruses (HPVs) are a family of small DNA viruses that infect epithelial cells of the skin and mucosa. They are highly specific to their respective host and have been shown to infect epithelial mucosa or cutaneous surfaces in almost all vertebrate species. Infection results in primarily benign, self-limiting warts or epithelial tumors. But among the HPVs infecting genital or aerodigestive mucosa, a certain number of the so-called high-risk viruses, including notably HPV 16 and HPV 18, induce lesions with an increased risk of progressing to cancer.¹ The role of these virus infections has been established by the regular presence of HPV DNA in retrospective tumor biopsy specimens, detailed molecular virology analyses, and epidemiologic studies pointing to these HPV infections as a major risk factor for cervical cancer. In addition to cancer of the cervix, a major proportion of anal, perianal, vulvar, and penile cancers appears to be linked to the same HPV infections.²

Since the development of sensitive methods of detecting HPV DNA in cancer tissue, the meaning of this infection regarding oncogenesis and new treatment strategies is increasing.

Clinical studies showed controversial data on the evidence of HPV in breast cancer. European studies mainly focused on HPV type 16 and 18,3, 4 but data from Chinese and Japanese women showed evidence of breast cancer associated with rare types of HPV, e.g. type 33.5, 6 We analyzed 81 women with biopsy-proven breast cancer for HPV infection using a PCR technique. To cover a broad range of HPV types we used six different primers analyzing over 40 different types of HPV including HPV 16, 18, 31, 33, and 45.

Section snippets

Patients

Ninety-two paraffin-embedded tissue samples from 81 breast cancer patients were obtained from the Pathology Department's archives. All patients were treated in the Department of Radiation Oncology, Inselspital, University of Bern, Switzerland during the period 1988–1998. Detailed information on the clinical and pathological characteristics of the patients analyzed are listed in Table 1. Every patient was treated with adjuvant local or loco-regional radiotherapy.

DNA isolation

About 10 μm sections were taken from each specimen and covered with ATL lysis buffer (Qiagen, Chatsworth, CA, USA). After xylol-ethanol removal as previously described,⁷ 20 μl of proteinase K (20 mg/ml; Fluka, Buchs, Switzerland) was added followed by incubation at 55 °C for 12 h. One hundred microns of aqueous NaCl solution (5 M) and 90 μl of CTAB (cetyltrimethyl-ammonium-bromide)/NaCl (10 g/0.7 M; Fluka) were added and incubated at 65 °C for 10 min. The sample was mixed with 800 μl of

Results

DNA was extracted from all samples for use for PCR amplification. The positive control was always positive. All tested samples were negative for the presence of HPV–DNA. Positive and negative studies of HPV–DNA in breast cancer and benign breast tissue are listed in Table 3, Table 4.

Discussion

The present study investigated breast cancer samples by using DNA PCR amplification of the conserved region within the L1 open reading frame of the papillomavirus genome. The SPF1/2 primers permit effective detection of 34 different anogenital HPV genotypes. In addition, they also allow detection of cutaneous HPV genotypes 3, 4, 5, 8, 27, 32, 37, 65, and 71. SPF1/2 is more sensitive than or equally sensitive to GP5+/6+ and My11/09.⁹ An overview of the discussed studies of breast cancer tissue

Conclusion

Our own analysis was not able to support a role of HPV infection in breast cancer. Controversial published data indicate a need for further larger epidemiologic studies.

Acknowledgments

The authors wish to thank Regula Buergi, Adrian Lehmann, and Bruno Streit for their excellent technical assistance.

Competing interests

The authors declare that they have no competing interests.

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ORIGINAL ARTICLEBreast cancer and human papillomavirus (HPV) infection: No evidence of a viral etiology in a group of Swiss women

Summary

Introduction

Section snippets

Patients

DNA isolation

Results

Discussion

Conclusion

Acknowledgments

Semin Cancer Biol

Pathol Res Pract

Am J Pathol

Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis

J Natl Cancer Inst

Absence of HPV 16 and 18 DNA in breast cancer

Br J Cancer

HPV33 DNA in premalignant and malignant breast lesions in Chinese and Japanese populations

Anticancer Res

Human papillomavirus type 33 DNA in breast cancer in Chinese

Breast Cancer

Papillomavirus in esophageal papillomas and carcinomas

Int J Cancer

PCR amplification from paraffin-embedded tissues. Effects of fixative and fixation time

Am J Clin Pathol

Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma

Cancer

ORIGINAL ARTICLE
Breast cancer and human papillomavirus (HPV) infection: No evidence of a viral etiology in a group of Swiss women