High risk human papilloma viruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer

Glenn WK, Ngan CC, Amos TG, Edwards RJ, Swift J, Lutze-Mann L, Shang F, Whitaker NJ & Lawson JS (2017): High risk human papilloma viruses (HPVs) are present in benign prostate tissues before development of HPV associated prostate cancer. Infectious Agents and Cancer 12:46.

Abstract

Background. Although high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active.

Methods. We used polymerase chain reaction (PCR) to identify HPVs in specimens from 52 Australian men with benign prostate biopsies who 1 to 10 years later developed prostate cancer. Immunohistochemistry (IHC) was used to assess the expression of HPV E7 oncoproteins, cytokeratin and prostate specific antigen (PSA).

We used RNASeq data from The Cancer Genome Atlas (TCGA) to identify possible HPV RNA sequences in prostate cancer.

Results. HPV screening using standard PCR was conducted on 28 of the 52 sets of benign and later prostate cancers. HPV L1 genes were identified in 13 (46%) benign and 8 (29%) of 28 later prostate cancers in the same patients. HPV E7 genes were identified in 23 (82%) benign and 19 (68%) of 28 subsequent prostate cancers in the same patients. The same HPV types were present in both the benign and subsequent prostate cancers in 9 sets of specimens. HPV type 16 was identified in 15% of benign and 3% of prostate cancers. HPV type 18 was identified in 26% of benign and 16% of prostate cancers. Small numbers of HPV types 45, 47, 76 and 115 were also identified.

High confidence RNA-Seq evidence for high risk HPV types 16 and 18 was identified in 12 (2%) of the 502 TCGA prostate cancer transcriptomes.

High risk HPV E7 oncoprotein was positively expressed in 23 (82%) of 28 benign prostate specimens but only in 8 (29%) of 28 of the later prostate cancer specimens. This difference is statistically significant (p = 0.001). Prostate specific antigen (PSA) was more highly expressed in 26 (50%) of 52 prostate cancer specimens as compared to prior benign prostate specimens in the same patients.

Conclusions. High risk HPVs are present in benign prostate tissues prior to the development of HPV positive prostate cancer. There is a significantly higher expression of HPV E7 oncoproteins in benign prostate tissues as compared to late prostate cancer that subsequently developed in the same patients. This observation suggests that HPV oncogenic activity is an early phenomenon in a majority of prostate oncogenesis. TCGA RNA-Seq data suggests that HPV is biologically active in some prostate tumour samples.

Emeritus Professor Jim Lawson has this to say about the study:

“Human papilloma viruses are the cause of cervical cancer in women. These viruses are sexually transmitted. Infections by human papilloma viruses can be prevented by effective vaccines including the Australian developed Gardosil.

Scientists from the University of New South Wales, Sydney, Australia, have identified high risk human papilloma viruses in normal prostate tissues 2 to 12 years before the development of human papilloma virus positive prostate cancer. While the scientists do not claim this is evidence that human papilloma viruses are a direct cause of prostate cancer, they advise that it is prudent for both men and women to act with caution.

Human papilloma viruses are present in semen in over 15% of men and can be readily transmitted during sexual activities.

Vaccines such as the Australian developed Gardosil, are safe and effective in preventing infections by human papilloma viruses. The University of New South Wales scientists strongly encourage both young men and women to prevent human papilloma virus infections by vaccination at a young age.”