ARTICLE IN PRESS The Breast (2007) 16, 222
THE BREAST www.elsevier.com/locate/breast
LETTER TO THE EDITOR HPV infection and breast cancer To the Editor, We read with great interest the article ‘‘Breast cancer and human papillomavirus (HPV) infection: no evidence of a viral etiology in a group of Swiss women’’.1 In this article, Lindel et al. failed to detect HPV DNA in 81 paraffin-embedded samples of breast cancer using L1 consensus PCR, calling into question the previously described association of breast cancer and HPV infection.2–4 We congratulate the authors for contributing to the literature on this important subject; however, we do no share their conclusion. It has been repeatedly demonstrated that PCR using primers targeting the L1 region is less reliable for detection of HPV infection than E6/E7 specific primers.5–7 There are two main reasons why L1 primers should not be used alone: (1) the L1/E1 regions, but never the E6/E7 regions, are lost during integration of viral DNA into host genomic DNA, a process that represents an essential component of progression from HPV infection to development of the malignant phenotype; and (2) the E6/E7 region exhibits less nucleotide variation.7 Rates of HPV detection are directly influenced by the type of PCR used in the analysis. Therefore, the negative results reported by the authors might only be reflecting technical limitations of the L1 consensus PCR. It would be necessary to reanalyze their tissue samples through additional type-specific PCRs, particularly using primers sets targeting the E6/E7 regions of the HPVs 16 and 18, in order to support their conclusions. Although the role of HPV in breast carcinogenesis remains controversial, we believe this might represent an important issue to be addressed in planning investigation of new preventive and
therapeutic strategies for patients with breast cancer in the future.
References 1. 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. 2. Hennig EM, Suo Z, Thoresen S, Holm R, Kvinnsland S, Nesland JM. 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. 3. Damin AP, Karam R, Zettler CG, Caleffi M, Alexandre CO. Evidence for an association of human papillomavirus and breast carcinomas. Breast Cancer Res Treat 2004;84:131–7. 4. Kan CY, Iacopetta BJ, Lawson JS, Whitaker NJ. Identification of human papillomavirus DNA gene sequences in human breast cancer. Br J Cancer 2005;93:946–8. 5. Noffsinger AE, Suzuk L, Hui YZ, Gall AA, Fenoglio-Preiser CM. Differential sensitivities of E6 type-specific and L1 consensus primers in the detection of human papillomavirus in anal carcinoma. Mod Pathol 1995;8:509–14. 6. Karlsen F, Kalantari M, Jenkins A, et al. Use of multiple PCR primer sets for optimal detection of human papillomavirus. J Clin Microbiol 1996;34:2095–100. 7. Morris BJ. Cervical human papillomavirus screening by PCR: advantages of targeting the E6/E7 region. Clin Chem Lab Med 2005;43:1171–7.
A.P. Damin, D.C. Damin, C.O.P. Alexandre Laboratory of Molecular Biology, Fundac- a˜o Faculdade Federal de Cie ˆncias Me´dicas de Porto Alegre, Porto Alegre, RS, Brazil E-mail address:
[email protected] (A.P. Damin)
0960-9776/$ - see front matter & 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2007.02.005
D.C. Damin Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil