Evidence for a causal role by human papillomaviruses in prostate cancer \u2013 a systematic review

James S Lawson,Wendy K Glenn

doi:10.1186/s13027-020-00305-8

Abstract

It is hypothesised that high risk for cancer human papillomaviruses (HPVs) have a causal role in prostate cancer.In 26 case control studies, high risk HPVs have been identified in benign and prostate cancers. High risk HPVs were identified in 325 (22.6%) of 1284 prostate cancers and in 113 (8.6%) of 1313 normal or benign prostate controls (p = 0.001).High risk HPVs of the same type have been identified in both normal and benign prostate tissues prior to the development of HPV positive prostate cancer. High risk HPVs can be associated with inflammatory prostatitis leading to benign prostate hyperplasia and later prostate cancer. Normal human prostate epithelial cells can be immortalised by experimental exposure to HPVs. HPVs are probably sexually transmitted.The role of HPVs in prostate cancer is complex and differs from HPVs associated cervical cancer. HPV infections may initiate prostate oncogenesis directly and influence oncogenesis indirectly via APOBEC enzymes. HPVs may collaborate with other pathogens in prostate oncogenesis.Although HPVs are only one of many pathogens that have been identified in prostate cancer, they are the only infectious pathogen which can be prevented by vaccination.A causal role for HPVs in prostate cancer is highly likely.

Highlights

We hypothesise that high risk for cancer human papillomaviruses (HPVs) have a causal role in prostate cancer
We sought to locate studies which (i) identified HPVs in normal, benign and malignant prostate tissues, (ii) assessed the presence of HPV antibodies in serum of normal men and prostate cancer patients, (iii) compared the prevalence of HPVs in normal, benign and prostate cancers, (iv) considered the outcome of prospective studies and in particular the presence of HPVs prior to the development of HPV positive prostate cancer, (v) investigated the capacity of HPVs to transform normal prostate cells into malignant cells (vi) investigated the HPV oncogenic mechanisms in prostate cancer and (vii) considered the potential means of HPV transmission
(viiiT) here is evidence that high risk HPVs can be associated with inflammatory prostatitis which can lead to benign prostate hyperplasia and later prostate cancer [87–91]

Summary

Introduction

We hypothesise that high risk for cancer human papillomaviruses (HPVs) have a causal role in prostate cancer. HPVs are only one of many pathogens that have been identified in prostate cancer, they are the only infectious pathogen which can be prevented by vaccination. We have assessed the evidence by using an extended version of the classic Austin Bradford Hill causal criteria [1]. We have included additional criteria to address more current scientific developments in studies of oncoviruses. These additional criteria include identification of the virus, means of transmission and oncogenic mechanisms. With respect to viruses and cancer, the conclusive identification of the virus in cancer tissues and a significant odds ratio between cancer and non-cancer tissues, are of special importance

Background

Methods

Discussion and conclusions

Findings

Conclusions