Abstract：
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 p16INK4a 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 p16INK4a 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.
摘要：
关于阴茎癌前病变的病理或分子研究很少，大多数是指与浸润性癌相关的病变。阴茎上皮内瘤变（PeIN）分为两个形态学和独特的分子组，非HPV和HPV相关的特殊亚型。这个国际系列的主要目的是对PeIN进行形态学分类，检测HPV基因型并根据PeIN亚型确定其分布。次要目的是评估p16INK4a免疫染色作为阴茎癌前病变中高危HPV感染的可能替代HPV。样本包括84例PeIN病例，1095例阴茎癌的回顾性横断面分析的一部分，旨在使用PCR和p16INK4a免疫染色评估阴茎癌中HPVDNA的患病率。阴茎上皮内瘤变(PeIN)被归类为HPV相关(基底细胞，warty-basaloid,Warty,混合动力车,和混合亚型）和非HPV相关（分化），前者是最频繁的。PEIN亚型被分化（非HPV相关）和基底细胞样，warty-basaloid,Warty,混合和混合（HPV相关）。BasaloidPeIN是最常见的诊断亚型，HPV16是最常见的HPV基因型。Warty-basaloid和wartyPeIN显示出更异质的基因型组成。大多数HPV基因型是高风险的，但在少数病例中也存在低风险的HPV基因型（4％）。在82%的HPV阳性病例中检测到单一HPV基因型。相比之下,在其余18%的病例中检测到多种基因型.这项研究的发现支持了阴茎原位瘤形成的范例，像它的侵入性对应物一样，是HPV依赖性的或不依赖性的，并且具有在常规实践中容易鉴定的独特形态亚型。考虑到HPV16显然是主要类型，并且三种可用的疫苗都具有HPV16，它们都将适合疫苗接种计划；疫苗的价格可能是选择疫苗的主要决定因素。
