Penile intraepithelial neoplasia: Distribution of subtypes, HPV genotypes and p16INK4a in 84 international cases

There are few pathologic or molecular studies of penile precancerous lesions, and the ma-jority refers to lesions associated with invasive carcinomas. Penile Intraepithelial Neoplasia (PeIN) is classified in two morphologically and distinctive molecular groups, non-HPV and HPV-related with special subtypes. The primary purpose of this international series was to classify PeIN morphologi-cally, detect HPV genotypes and determine their distribution according to PeIN subtypes. A secondary aim was to evaluate the p16INK4a immunostaining as a possible HPV surrogate for high-risk HPV infec-tion in penile precancerous lesions. Samples consisted of 84 PeIN cases, part of a retrospective cross-sectional analysis of 1095 penile carcinomas designed to estimate the HPV DNA prevalence in penile cancers using PCR and p16INK4a immunostaining. Penile Intraepithelial Neoplasia (PeIN) was classi-fied in HPV-related (basaloid, warty-basaloid, warty, hybrid, and mixed subtypes) and non-HPV-related (differentiated), the former being the most frequent. PeIN subtypes were differentiated (non-HPV-related) and basaloid, warty-basaloid, warty, hybrid and mixed (HPV-related). Basaloid PeIN was the most commonly diagnosed subtype, and HPV16 was the most frequent HPV genotype detected. Warty-basaloid and warty PeIN showed a more heterogeneous genotypic composition. Most HPV ge-notypes were high-risk but low-risk HPV genotypes were also present in a few cases (4%). A single HPV genotype was detected in 82% of HPV positive cases. In contrast, multiple genotypes were de-tected in the remaining 18% of cases. The findings in this study support the paradigm that penile in situ neoplasia, like its invasive counterparts, is HPV dependent or independent and has distinctive morpho-logical subtypes readily identified in routine practice. Considering that HPV16 is clearly the predom-inant type, and that the three available vaccines have HPV16, all of them will be suitable for vaccination programs; the price of the vaccines will be probably the main determinant to choose the vaccine.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

There is limited research on pathologic and molecular studies of penile precancerous lesions, particularly non-invasive lesions. This study aimed to classify Penile Intraepithelial Neoplasia (PeIN) based on morphology and detect HPV genotypes, as well as evaluate p16INK4a immunostaining as a potential surrogate for high-risk HPV infection. The findings show distinct morphological subtypes of PeIN and highlight the importance of HPV in the development of penile in situ neoplasia.