Human Papillomavirus (HPV) Genotypes in Mixed Squamous Cell Carcinoma of the Penis: A Study of 101 Tumors

Squamous cell carcinomas with two or more coexisting clearly different histological subtypes of penile carcinomas are designated as mixed carcinomas in current classification models. They represent about 10% of all penile carcinomas. The aim of this study was to detect HPV genotypes in these unusual tumors. Tumors were selected from an international series of 1010 patients with penile carcinomas. Mixed carcinomas were grouped, according to WHO recommendations, as follows: 1. Carcinomas with warty/basaloid features mixed with HPV-independent carcinomas and 2. HPV-independent subtypes mixed with each other. HPV detection and p16^INK4a immunostaining were performed. For HPV detection, whole tissue section-PCR analyses were performed by SPF10-DEIA-LiPA25 (version 1). As expected, HPV was detected more frequently in HPV-associated mixed carcinomas than in HPV-independent mixed carcinomas. Carcinomas with basaloid or warty features mixed with other SCC subtypes showed an HPV positivity rate of 46% (33 of 72 tumors) compared with 7% found in tumors with nonwarty/basaloid morphology (2 of 29 tumors). Eleven high-risk HPV genotypes were identified and the most common was HPV16 (65%) usually associated with basaloid morphology. p16^INK4a immunostaining was positive in 76% of HPV-positive tumors. As in nonmixed carcinomas, although in lower proportion, a variable array of HPV genotypes was detected in mixed carcinomas. Apparently, the presence of a non-HPV component in an otherwise typical HPV-associated type tumor does adversely affect the prevalence of HPV positivity. Any amount of HPV-associated morphology superior to 20% in a mixed tumor is sufficient to classify them as HPV-associated, a WHO requirement.