Koilocytes indicate a role for human papilloma virus in breast cancer

Abstract

BACKGROUND: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. METHODS: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. RESULTS: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). INTERPRETATION: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.

No Detection of 'High-risk' Human Papillomaviruses in a Group of Iranian Women with Breast Cancer

“…Human papilloma virions are known to be released when the cornified envelope of cells desquamate; accordingly, HPVs can be transmitted by skin-to-skin contact as well as by sexual activity (Bryan and Brown, 2001). Lawson et al (2009) reported that cell surfaceto-surface contact mainly during sexual activities is required for HPV transmission and modulation of cellular pathways. According to a study, HPV is mainly found on the dermis of the breast and travels through the nipple and ducts, infects the breast tissue and starts the potential malignant process (De Villiers et al, 2005).…”

The Active Form of E6-associated protein (E6AP)/UBE3A Ubiquitin Ligase Is an Oligomer

“…Although p53 degradation is normally mediated by the Mdm2 ubiquitin ligase (34), E6 protein is proposed to bind to E6AP and redirect its specificity to p53 (33,35). Enhanced degradation of p53 in epithelial cells by the HPV16 and -18 viral strains induces cell transformation and development of cervical and oral cancers, depending on the site of infection (5,36,37). Similarly, hepatitis C virus encodes the NS5B protein that binds E6AP and induces degradation of the retinoblastoma protein tumor suppressor, increasing the risk of liver cirrhosis and hepatocellular carcinoma (38,39).…”

Investigation of human papillomaviruses (HPV), mouse mammary tumour virus (MMTV), Epstein–Barr virus (EBV), and human polyomavirus entities in canine mammary tumours

“…About 4-5 m-thick paraffin sections were stained with haematoxylin and eosin, evaluated under a light microscope, and classified according to the WHO classification (17). The existence of koilocytes (nuclear enlargement with clear perinuclear cytoplasmic halo), which were accepted as pathognomonic for HPV (12), was also evaluated.…”