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

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.

SUBMITTER: Glenn WK

PROVIDER: S-EPMC5553674 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Glenn Wendy K WK Ngan Christopher C CC Amos Timothy G TG Edwards Richard J RJ Swift Joshua J Lutze-Mann Louise L Shang Fei F Whitaker Noel J NJ Lawson James S JS

Infectious agents and cancer 20170811

<h4>Background</h4>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 biologicall ...[more]

PMID: 28811834

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Project description:PURPOSE:Human papillomaviruses (HPV) may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i) confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii) evidence of HPV infections in benign breast tissues prior to the development of HPV-positive breast cancer in the same patients, (iii) evidence that HPVs are biologically active and not harmless passengers in breast cancer. METHODS:RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR) analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active,?the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC). RESULTS:Thirty (3.5%) low-risk and 20 (2.3%) high-risk HPV types were identified in 855 breast cancers from the TCGA database. The high risk types were HPV 18 (48%), HPV 113 (24%), HPV 16 (10%), HPV 52 (10%). Data from the PCR cohort study indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens) followed by HPV 16 (13%). The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens. CONCLUSION:There were four observations of particular interest: (i) confirmation by both NGS and PCR of the presence of high-risk HPV gene sequences in breast cancers, (ii) a correlation between high-risk HPV in benign breast specimens and subsequent HPV-positive breast cancer in the same patient, (iii) HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of HPV E7 proteins), (iv) HPV oncogenic influences may occur early in the development of breast cancer.

Project description:Intra-tumor heterogeneity (ITH) has been studied at the morphologic, genomic, and transcriptomic level, but not proteomic level. Recent advances in mass spectrometric (MS) proteome quantification techniques, exemplified by SWATH-MS, a massively parallel targeting method, now also support precise quantitative proteomic comparisons across multiple samples, thus identifying molecular and implied functional differences. Here we used SWATH-MS to analyze the proteome profiles of a set of fresh-frozen prostate tissue samples derived from radical prostatectomy specimens. A high confidence set of 1,906 proteins were consistently quantified across 60 biopsy-level tissue samples from three prostatectomy patients, each consisting of 1.0 mm punch biopsies from histologically malignant (acinar and ductal adenocarcinoma) and matching benign prostatic hyperplasia tissues. The quantitative protein profiles allowed independent quantification of the degree of intra-tumor heterogeneity for each protein in benign and malignant tissues. We found that while majority of the proteins showed comparably low intra-tumor variability, 122 proteins were highly variable in malignant and/or matching benign tissues. We observed that proteins that varied between patients or tissue types also tended to be highly variable within prostate tissues, suggesting that these variability patterns will be a critical selection criterion in future protein biomarker studies. The data also permitted investigation of the heterogeneity of multiple biochemical pathways. The high variability of several of the pathways, including Glypican-1 network, alpha-linolenic acid metabolism and celecoxib pathway, explained contradictory results regarding them in the literature. In conclusion, we demonstrated a methodology for investigating proteomic intra-tumor heterogeneity from biopsy-level tissue samples, and quantified the degree of intra-tumor heterogeneity of 1,906 proteins in prostate tumors. The method and data presented here have advanced our understanding of tumor biology and offered critical insights for future biomarker development.

Dataset Information

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

Publications

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

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