Penile squamous cell carcinomas with the usual-type morphology can be HPV-associated – Routine p16/HPV testing should be performed in all penile squamous cell carcinomas regardless of morphology

Usual-type penile squamous cell carcinoma (pSCC) is the most common pSCC subtype, categorized under the HPV-independent pSCC category in the WHO classification. Currently, guidelines do not explicitly recommend routine HPV testing in pSCCs, and pSCCs with the usual-type morphology are often presumed to be HPV-independent without further testing. This study investigates the HPV status in pSCCs with the usual-type morphology. Fifteen consecutive pSCCs with the usual-type morphology were retrospectively identified. p16 immunohistochemistry was diffusely positive in three of the fifteen pSCCs with the usual-type morphology (3/15; 20%), confirmed by high-risk HPV in situ hybridization. As routine HPV testing is not explicitly recommended in the pSCCs with the usual-type morphology, there could be a significant number of the pSCCs incorrectly presumed to be HPV-independent. As the HPV status in pSCCs carries significant clinical consequences, routine HPV testing should be considered in all pSCCs with the usual-type morphology.