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Penile intraepithelial neoplasia (PeIN) is currently classified in human papillomavirus (HPV)- and non-HPV-related subtypes with variable HPV genotypes. PeINs are frequently associated with other intraepithelial lesions in the same specimen. The aim of this study was to detect and compare HPV genotypes in PeINs and associated lesions using high-precision laser capture microdissection-polymerase chain reaction and p16INK4a immunostaining. We evaluated resected penile specimens from 8 patients and identified 33 PeINs and 54 associated lesions. The most common subtype was warty PeIN, followed by warty-basaloid and basaloid PeIN. Associated lesions were classical condylomas (17 cases), atypical classical condylomas (2 cases), flat condylomas (9 cases), atypical flat condylomas (6 cases), flat lesions with mild atypia (12 cases), and squamous hyperplasia (8 cases). After a comparison, identical HPV genotypes were found in PeIN and associated lesions in the majority of the patients (7 of 8 patients). HPV16 was the most common genotype present in both PeIN and corresponding associated lesion (50% of the patients). Nonspecific flat lesions with mild atypia, classical condylomas, and atypical condylomas were the type of associated lesions most commonly related to HPV16. Other high-risk HPV genotypes present in PeIN and associated nonspecific flat lesion with mild atypia were HPV35 and HPV39. In this study of HPV in the microenvironment of penile precancerous lesions, we identified identical high-risk HPV genotypes in PeIN and classical, flat, or atypical condylomas and, specially, in nonspecific flat lesions with mild atypia. It is possible that some of these lesions represent hitherto unrecognized precancerous lesions. [ABSTRACT FROM AUTHOR]

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 p16INK4a 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. p16INK4a 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. [ABSTRACT FROM AUTHOR]