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Histological grade and depth of invasion are among the best outcome pathological predictors in penile cancer. The TNM system is based on a combination of both for some stages. It is assumed that high-grade and deep tumors carry the worst prognosis, and the opposite occurs with superficial and low-grade neoplasms. However, there is no systematic evaluation of the phenomenon. We studied 147 patients from the Hospital de Oncologia - Instituto Mexicano del Seguro Social (period 2000 to 2013). They were treated by total or partial penectomies. Lymph node involvement was evaluated by bilateral inguinal node dissection (126 cases) or ultrasonography (21 cases). Tumor thickness was measured in mm from tumor surface to deepest invasion point, using a cut-point for superficial (≤10 mm) vs deep (>10 mm) tumors. Histological grade was from 1 to 3 according to WHO and AFIP criteria and considering G1 and G2 as low-grade and G3 as high-grade. Average age was 62 (26-98) years old. Tumor thickness mean was 15 mm (2-30 mm). G1, G2 and G3 tumors corresponded to 19 (13 %), 48 (33 %), and 80 (54 %) cases, respectively. Follow-up ranged from 10 to 82 months (median: 57 months). Fifty-three (36 %) patients died of disease. There was an overall correlation of tumor thickness and grade in most of the cases. Low-grade tumors were encountered in 92 % (12/13 cases) of superficial tumors. Deep tumors showed high-grade in 75 % of cases (73/97 cases). Superficial tumors with low histological grade had negative inguinal nodes and no mortality whereas deep tumors showing high histological grade were associated with high metastatic risk to lymph nodes (62/73 cases) and mortality (52/73 cases). Out of 24 deep tumors with low histological grade, seven had nodal spread (29 %) but only one died of disease. No outcome difference was found in HPV associated vs HPV independent tumors. Tumor thickness and grade are important synergistic and predictive pathological factors in relation to prognosis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human papillomavirus (HPV) is detected in 30-50% of invasive penile carcinomas, and it is frequently associated with basaloid and warty morphological features. Based on this heterogeneity and different clinical behaviors, we hypothesized a variation in their HPV genotypic composition. To test this, we evaluated 177 HPV-positive cases: basaloid (114), warty-basaloid (28), and warty (condylomatous) (35) invasive carcinomas. HPV DNA detection and genotyping was performed using the SPF-10/DEIA/LiPA 25 system. Nineteen HPV genotypes were detected. High-risk HPVs predominated (96%), and low-risk HPVs were rarely present. Most common genotype was HPV16 followed by HPVs 33 and 35. According to the genotypes identified, 93% of the cases would be covered with current vaccination programs. There was a significant variation in the distribution of HPV16 and non-HPV16 genotypes according to histological subtype. HPV16 was significantly frequent in basaloid (87%) and was less frequent in warty carcinomas (61%). This molecular difference, along with their distinctive macro-microscopic and prognostic features, makes basaloid and warty carcinomas unique. The gradual decreasing frequency of HPV16 demonstrated in basaloid, warty-basaloid, and warty carcinomas suggest that the basaloid cell, present in those types in decreasing proportions, may be responsible for the differences., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There are few pathologic or molecular studies of penile precancerous lesions, and the majority 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 morphologically, detect HPV genotypes and determine their distribution according to PeIN subtypes. A secondary aim was to evaluate the p16 INK4a immunostaining as a possible HPV surrogate for high-risk HPV infection 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 p16 INK4a immunostaining. Penile Intraepithelial Neoplasia (PeIN) was classified 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 genotypes 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 detected 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 morphological subtypes readily identified in routine practice. Considering that HPV16 is clearly the predominant 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)