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.

Virchows Archiv : an international journal of pathology. 2026 Jun 24 [Epub ahead of print]

Dane Wuori, Nicole A Cipriani, Melissa Y Tjota, Levent Trabzonlu, Vaibhav Chumbalkar, Julieta Barroeta, Tatjana Antic, Jung Woo Kwon

Department of Pathology, University of Chicago, Chicago, IL, USA., Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA., Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA., Department of Pathology, University of Chicago, Chicago, IL, USA. .