Presence of human papillomavirus in human prostate

Abstract

Background: Prostate cancer is the most commonly diagnosed cancer in Australian men. Recent literature suggests that chronic inflammation has an important role in the pathogenesis of prostate cancer, but the cause of inflammation remains elusive. Chronic inflammation may be due to infection and human papillomavirus (HPV) is one of the potential causative organisms. Previous studies on the relationship between high-risk HPV and prostate cancer were inconclusive. Most molecular studies utilised standard PCR to detect HPV sequences in DNA isolated from prostate cancer specimens. We aimed to utilise a more sensitive molecular amplification technique to detect the presence of HPV in DNA extracted from prostate specimens. In parallel, we aimed to demonstrate the presence of HPV in prostate specimens and identify its cellular location by a non-amplification in situ technique. Methods: We performed real-time PCR using GP5+/6+* primers on DNA extracted from 72 paraffin-embedded formalin-fixed (FFPE) prostate specimens. Samples identified as potentially HPV positive were confirmed by sequencing. Chromogenic in situ hybridisation (CISH) was optimised on cervical cancer cell lines and FFPE cervical cancer specimens, and then applied to HVP screening on the same prostate specimens. Results: High-risk HPV was identified in a proportion of prostate specimens. HPV was detected in 6/36 normal/benign prostate specimens and 4/36 prostate cancer specimens. All positive samples except one genotyped to HPV18. CISH was successfully established in cervical cancer cell lines and FFPE cervical cancer specimens. One benign prostate specimen and one prostate cancer specimen were HPV positive by CISH. Due to significant background signals, HPV status could not be determined on a large number of prostate specimens. Conclusion: The real-time PCR result presented in this thesis demonstrated the presence of high risk HPV in some prostate specimens. Further study is required to determine whether HPV is biologically active in these cases. Real-time PCR followed by an in situ technique can be an effective strategy for HPV screening on FFPE specimens.