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Human papillomavirus (HPV) and p16INK4a expression in early-onset prostate cancer

Int Urol Nephrol. 2026 Jun 3. doi: 10.1007/s11255-026-05218-w. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the potential role of human papillomavirus (HPV) in early onset prostate cancer (PCa) through HPV-DNA detection and genotyping, and immunohistochemical evaluation of p16INK4a expression.

METHODS: This retrospective cross-sectional study included patients diagnosed with PCa at ≤ 55 years of age between 2010 and 2021. Patients with a familial history of PCa, incomplete medical records, immunodeficiency, or insufficient tissue for molecular analysis were excluded. Formalin-fixed, paraffin-embedded (FFPE) prostate biopsy samples were analyzed for HPV-DNA using the HPV 3.5 LCD-Array Kit (Chipron GmbH, Berlin, Germany), a multiplex PCR-based assay targeting 32 HPV genotypes. Immunohistochemical staining for p16INK4a was performed to assess its expression. Clinical data, including PSA levels, Gleason score, ISUP grade, and EAU risk group, were compared between HPV-positive and HPV-negative cases.

RESULTS: HPV-DNA was detected in 12 of 45 cases (26.7%), with genotype 62 being the most frequent. Multiple HPV genotypes were identified in three cases (6.7%). p16INK4a immunopositivity was observed in 91.7% of HPV-positive tumors compared with 69.7% of HPV-negative tumors (p = 0.240). HPV-positive patients showed higher ISUP grades than HPV-negative patients (p = 0.029) and were more likely to be in intermediate or high-risk groups (p = 0.028). No significant differences were observed in PSA levels or Gleason scores.

CONCLUSION: The detection of HPV-DNA in a considerable proportion of early onset PCa specimens, together with the more frequent but not statistically significant p16INK4a positivity in HPV-positive tumors, suggests a possible association with prostate tumor biology. However, the presence of low-risk HPV genotypes and the non-specific nature of p16INK4a expression complicate the interpretation of a direct oncogenic role.

PMID:42234298 | DOI:10.1007/s11255-026-05218-w

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