Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer.

Prostate. 2013 Feb 15;73(3):236-41.

Whitaker NJ, Glenn WK, Sahrudin A, Orde MM, Delprado W, Lawson JS.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.


INTRODUCTION: The purpose of this study is to determine if high risk human papillomaviruses (HPV) and Epstein Barr virus (EBV) are both present in the same prostate cancer specimens.

METHODS: We used a range of analytical techniques including in situ polymerase chain reaction (IS-PCR) and standard liquid PCR followed by sequencing of the product to seek to identify HPV and EBV in normal, benign, and malignant prostate tissues.

RESULTS: Both HPV type 18 and EBV gene sequences were identified in a high and approximately equal proportion of normal, benign, and prostate cancer specimens. These sequences were located in the nuclei of prostate epithelial cells. HPV associated koilocytes were identified in 24% of prostate cancer specimens.

CONCLUSIONS: The presence of both HPV and EBV gene sequences in most of the same normal, benign, and malignant prostate specimens is particularly noteworthy because of recent experimental evidence demonstrating that EBV and HPV can collaborate to increase proliferation of cultured cervical cells. Because the presence of EBV and HPV in normal, benign, and malignant prostate tissues appears to be ubiquitous, it is possible that they are harmless. On the other hand HPV type 18 in particular, has high oncogenic potential and may be associated with some prostate cancers. The identification of HPV associated koilocytes in prostate cancer specimens is an indication of HPV infection and potential oncogenic influences of human papillomavirus in prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

PMID: 22851253



The possible role of human papilloma virus (HPV) in a wide range of human cancers in addition to cervical cancer, is gradually being realised. HPVs have been identified in prostate, breast, colon and head and neck cancers and even in lung cancer. However there is doubt whether HPV has a causal role in these cancers or is merely a harmless passenger.

This Australian study by Noel Whitaker and colleagues has confirmed that high risk for cancer HPVs are present, in approximately equal proportions, in normal, benign and malignant prostate tissues. They have also shown that HPVs are frequently present in association with Epstein Barr virus (EBV) another well known the cancer causing virus.

These findings demonstrate the complex problem of determining whether viruses cause cancer. The main problem is that infections by viruses such as HPV and EBV are very common but rarely cause cancer. An additional complexity is that these viruses may require the influence of cofactors to cause cancer. These cofactors may include the influence of hormones, the immune system and even interactions between viruses.

It is for these reasons that Whitaker and colleagues have sought to identify specific indicators that viruses such as HPV, are acting oncogenically in specific tissues such as the prostate. They have done this by the recognition of koilocytes. Koilocytes are specific to HPV infections and form the basis of screening for cervical precancers. Koilocytes are epithelial cells with acentric nuclei surrounded by a vacuolated halo and can be readily recognised by light microscopy. In this current study, HPV positive koilocytes were recognised in both benign and malignant prostate tissues which is a strong indication that high risk HPVs probably have an oncogenic influence in some prostate cancers.

James Lawson-1

Human papilloma virus positive prostate intraepithelial neoplasia as shown by in situ PCR.

This image shows the location of HPV type 18 in precancerous epithelial cells of the prostate gland.

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