Shigehara K, et al. World J Mens Health. 2024 Oct;42:e89. https://doi.org/10.5534/wjmh.240066

Human papillomavirus (HPV) is common in both sexes and is also detected in male urine and semen. However, its exact origin and its etiological role in the male genital tract remain unclear. A total of 157 formalin-fixed paraffin-embedded tissues from 156 primary prostate cancer lesions and one metastatic lesion were analyzed. HPV-DNA was detected using a nested PCR, and HPV genotyping was performed using flow-through hybridization for positive cases. In situ hybridization (ISH) was used to localize HPV-DNA, whereas HPV-E6/E7 mRNA ISH and p16^INK4a immunohistochemistry were conducted on high-risk (HR) HPV-positive samples. A nested PCR analysis demonstrated that HPV-DNA was detected in 9.6% of prostate cancers and 0% of seminal vesicles. HR-HPV was observed in 4.5% of the samples. Unknown type was the most common genotype. Of the genotypes which could be identified in the genotyping assay, HPV44 was the most prevalent. HPV prevalence was significantly higher in patients with high-grade groups. Among 15 HPV-positive cases, HPV-DNA was found in 9 cancerous and 10 non-cancerous lesions. E6/E7 mRNA was expressed in 6 of 7 HR-HPV-positive cases, while p16^INK4a expression was weak or absent in all cases. HPV can infect prostate tissue and may contribute to carcinogenesis in some cases, but p16^INK4a was not a consistent surrogate for E7 expression.

Human papillomavirus (HPV) is common in both sexes and is also detected in male urine and semen. However, its exact origin and its etiological role in the male genital tract remain unclear. Formalin-fixed paraffin-embedded tissues from 157 prostate cancer patients were analyzed. HPV-DNA was detected using a nested PCR reaction, and HPV genotyping was performed using flow-through hybridization for positive cases. In situ hybridization (ISH) was used to localize HPV-DNA, whereas HPV-E6/E7 mRNA ISH and p16INK4a immunohistochemistry were conducted on high-risk (HR) HPV-positive samples. HPV-DNA was detected in 9.6% of prostate cancers and 0% of seminal vesicles. HR-HPV was observed in 4.5% of the samples, with HPV44 being the most common genotype. HPV prevalence was significantly higher in patients with high-grade groups (GG 4–5). Among 15 HPV-positive cases, HPV-DNA was found in 9 cancerous and 10 non-cancerous lesions. E6/E7 mRNA was expressed in 6 of 7 HR-HPV-positive cases, while p16INK4a expression was weak or absent in all cases. HPV can infect prostate tissue and may contribute to carcinogenesis in some cases, but p16INK4a may not be a consistent surrogate for E7 expression.

This study investigated the prevalence, genotypes, and tissue localization of human papillomavirus (HPV)-DNA in testicular tumor including epididymis and spermatic cord specimens from 116 Japanese patients who underwent radical inguinal orchiectomy. Formalin-fixed, paraffin-embedded tissues were analyzed by nested polymerase chain reaction (PCR), followed by sequencing-based HPV genotyping. HPV-DNA localization was assessed by in situ hybridization (ISH), and E6/E7 mRNA ISH was performed in HPV-positive specimens. HPV-DNA was detected in three patients (3/116, 2.6%), including one testicular tumor specimen (1/116, 0.9%) and two spermatic cord specimens (2/116, 1.7%). All HPV-positive specimens contained HPV16-DNA. HPV-DNA ISH signals were observed in seminoma cells in one testicular specimen and in the vas deferens epithelium in one spermatic cord specimen. On the other hand, ISH signals were not present in epididymis tissue in the HPV-positive testicular tumor tissue, suggesting that HPV-DNA detection rate of epididymis was 0%. E6/E7 mRNA signals were not detected in any HPV-positive specimen. These findings demonstrate that HPV16-DNA was surely present in testicular tumor and the vas deferens epithelium. However we could not provide evidence of transcriptionally active HPV oncogenes, and could not establish a causal role in testicular tumorigenesis.

We investigated the anatomical distribution of human papillomavirus (HPV) infection in the lower urinary tract of men with bladder cancer undergoing radical cystectomy. In total, 79 anterior urethral samples, 99 prostatic urethral specimens, 74 bladder tumor specimens, and 87 non-tumor bladder specimens were collected from 102 patients. After DNA extraction from each formalin-fixed paraffin-embedded tissue specimen, HPV-DNA was examined by nested polymerase chain reaction, and HPV genotypes were determined by Sanger sequencing. In situ hybridization (ISH) was used to localize HPV-DNA in positive samples, and E6/E7 mRNA ISH was performed to assess transcriptional activity. HPV-DNA was detected at any site in 16 (15.7%) of 102 patients, with site-specific detection rates of 8.0% (7/87) in non-tumor bladder mucosa, 5.1% (4/79) in the anterior urethra, 4.1% (3/74) in bladder tumor tissue, and 4.0% (4/99) in the prostatic urethra. HPV16 was detected in 11 samples, and HPV18 in 7 samples. HPV-DNA ISH signals were observed in 12 (66.7%) of 18 HPV-positive specimens, and E6/E7 mRNA signals were present in 2 of 18 specimens. HPV-DNA was detected at various sites of the lower urinary tract. E6/E7 mRNA expression in a bladder cancer specimen warrants further research on the biological relevance of HR-HPV infection.