The role of human papillomavirus (HPV) in prostate cancer development remains uncertain, despite accumulating evidence of a potential link in certain populations. While HPV is a known cause of several epithelial cancers, its connection to prostate cancer (PCa) has not been definitively proven. This research assessed the immunohistochemical presence of high-risk HPV E6/E7 oncoproteins in prostate cancer and benign prostatic hyperplasia (BPH) tissues from a Sudanese cohort and explored their association with clinicopathological features.

A retrospective case-control study involved 100 prostate tissue specimens fixed in formalin and embedded in paraffin, consisting of 50 histologically confirmed PCa cases and 50 BPH controls. The expression of high-risk HPV E6/E7 proteins was assessed by immunohistochemistry with monoclonal antibodies, and staining was semi-quantitatively scored using the H-score system. The relationship between HPV immunoreactivity and clinicopathological variables was analyzed using various statistical tests, including chi-square tests, Mann-Whitney U tests, logistic regression, and odds ratio calculations.

High-risk HPV E6/E7 immunoreactivity was significantly more common in prostate cancer than in benign prostatic hyperplasia (48% vs. 18%; p = 0.0026). Prostate cancer tissues had over four times higher odds of HPV positivity compared to benign tissues (OR = 4.21, 95% CI: 1.69–10.43). Positive immunostaining was significantly associated with higher ISUP Grade Groups (p = 0.0035) and advanced tumor stages (p = 0.004), while no significant association was found with serum prostate-specific antigen (PSA) levels. Multivariable logistic regression confirmed that higher tumor ISUP grade and pathological stage were independently associated with HPV E6/E7 immunoreactivity, even after adjustment for PSA.

In this Sudanese cohort, high-risk HPV E6/E7 immunoreactivity was associated with prostate cancer and more severe pathological features. These results suggest a possible connection between HPV-related protein expression and aggressive tumor traits. However, since immunohistochemistry alone cannot confirm active HPV infection or prove its causal role in prostate cancer development, caution is needed when interpreting these findings. Future research should include molecular HPV detection, viral genotyping, and RNA-based studies to better understand HPV’s biological role in prostate cancer.