Is HPV infection a hidden risk factor for prostate cancer?

By Dr. Priyom Bose, Ph.D.Oct 8 2023Reviewed by Benedette Cuffari, M.Sc.

In a recent Scientific Reports study, scientists conducted a meta-analysis to examine the role of human papillomavirus (HPV) in prostate carcinogenesis.

Study: Human papillomavirus and prostate cancer: Systematic review and meta-analysis. Image Credit: Corona Borealis Studio / Shutterstock.com

The epidemiology of prostate cancer

Prostate cancer is a significant health problem and the fifth leading cause of death in men worldwide. The prevalence of prostate cancer varies across different regions, with the highest prevalence reported in Northern and Western Europe, North America, South Africa, Australia/New Zealand, and the Caribbean, whereas the lowest incidence of prostate cancer has been recorded in Asia and North Africa. This variability in the incidence rate of prostate cancer has been attributed to different socioeconomic status and health policies of other countries. 

Some risk factors associated with prostate cancer include age, genetic predisposition, and family history. Previously, researchers have reported that HOXB13 mutation increases the risk of prostate cancer. Other genes associated with prostate cancer include BRCA1, BRCA2, and the MSH2 gene.

Ethnicity also plays a prominent role in the manifestation of prostate cancer. Compared to Asian men, for example, black men in the United States and the Caribbean have the highest rate of prostate cancer.

HPV and cancer

About 15% of all human cancers are associated with viruses. Some viruses can modify the behavior of tumor cells by blocking apoptosis pathways, triggering angiogenesis, inhibiting tumor suppressor signaling, and promoting metastasis.

Although HPV is associated with cervical cancer in women, it does not appear to increase the risk of ovarian and endometrial cancer.

A previous study has indicated that HPV infection influences prostate cancer pathogenesis. Likewise, genetic and clinical studies have indicated a potentially causal relationship between HPV and prostate cancer.

This observation was based on identifying HPV-associated koilocytes in prostate cancer samples. A higher expression of HPV E7 oncoproteins was also found in benign prostate tissues compared to advanced prostate cancer.

Nevertheless, some studies have contradicted the idea of HPV being associated with the incidence of prostate cancer. Thus, the exact role of HPV in prostate cancer incidence is unclear. 

About the study

The current meta-analysis obtained all relevant studies from publicly available bibliometric databases, including Embase, PubMed, Medline, and Scopus, from their inception to August 21, 2022. The study considered research with morphologically confirmed prostate cancer diagnosis and HPV presence by polymerase chain reaction (PCR) assay.

HPV infection increases the risk of prostate cancer as compared to normal tissues, not BPH

The initial search resulted in a total of 271 articles. After removing duplicates and considering all eligibility criteria, 27 case-control studies were considered.

These studies included analyses of 1,607 prostate tumor tissue samples and 1,443 control samples. The tumor prostrate sample was considered the study sample, whereas normal prostate and benign prostatic hyperplasia (BPH) tissues were considered the control.

The link between the risk of prostate cancer and HPV infection is significant when normal prostate tissue is considered the control. Comparatively, when BPH was considered a control, this association was not statistically significant. This finding revealed that the type of control tissue impacts the association between HPV infection and prostate cancer risk.

In 1990, the presence of HPV types 16 and 18 was first detected in prostate cancer tissues. This study highlighted that normal prostate tissue or BPH as a control impacted the study outcome.

BPH samples have a quantitative advantage compared to normal tissue, as HPV detection frequency in BPH is higher. Therefore, no significant association between HPV infection and BPH was found in these studies.

HPV infection is a "hit and run" phenomenon, in which a complete or incomplete viral genome is detected only in the early stage of prostate cancer. It becomes undetectable in the later stage of cancer. High-risk HPV types 16 and 18 are commonly present in BPH tissues for one to 10 years before developing HPV-positive prostate cancer. 

In addition to detecting the presence of HPV, it is important to determine the physical status of the HPV genome in HPV-positive samples. During carcinogenesis, HPV DNA is present in an integrated form characterized by overexpression of E6 and E7 genes. HPV infection could also aid in increasing the resistance to apoptosis in human prostate tumor cells.

Conclusions

The current study indicated that HPV infection increases men's prostate cancer risk. In the future, more research is needed to elucidate the precise role of HPV in the development of prostate cancer, in which normal prostate tissues, rather than BPH samples, serve as control.