Institute of Pathology, Medical University Graz, Austria.
Am J Surg Pathol. 2011 Jul;35(7):998-1006. doi: 10.1097/PAS.0b013e3182147e59.
Human papillomavirus (HPV) infections account worldwide for 50% of penile cancers. The role of lichen sclerosus and lichen planus in penile carcinogenesis needs further investigation.
Archival formalin-fixed high-grade penile intraepithelial neoplasias, differentiated penile intraepithelial neoplasias, and invasive carcinomas from a single pathology institution in a low-incidence area for penile cancer were analyzed for 28 HPV low-risk and HPV high-risk genotypes, p16 overexpression, presence of peritumoral lichen sclerosus, lichen planus, precursor lesions, and monoclonal rearrangement of the T-cell receptor γ locus.
A total of 29 penile intraepithelial neoplasias (100%) and 69 of 115 (60%) invasive cancers contained HPV high-risk genotypes with a single HPV high-risk genotype (80% HPV16, 6% HPV33, 2% HPV45 and HPV18, 1% HPV73). Multiple HPV high-risk genotypes were identified in 4% with and in 5% without HPV16/18. p16 overexpression correlated in all but 1 case of HPV high-risk 45 cancer. No p16 overexpression and HPV genotype was found in 6 differentiated penile intraepithelial neoplasias and 46 of 115 (40%) invasive cancers, 30% of which were pT2/pT3 cancers. For 35 cancers, peritumoral tissue was available for analysis. Advanced lichen sclerosus was identified in 26, lichen planus in 9, and differentiated penile intraepithelial neoplasia in 18 carcinomas. Dense T-cell-dominant lymphocytic infiltrates were identified in 22 of 46 carcinomas and in 3 of 6 differentiated penile intraepithelial neoplasias, with 6 of 13 analyzed carcinomas/penile intraepithelial neoplasias showing a monoclonal rearrangement of the T-cell receptor γ locus.
The prevalence of HPV high-risk in penile cancers from a low-incidence area was slightly higher than the global distribution. HPV-negative carcinomas were associated with advanced lichen sclerosus and lichen planus, differentiated penile intraepithelial neoplasia, and accumulation of T lymphocytes with monoclonal rearrangement of the T-cell receptor γ locus.
人乳头瘤病毒（HPV）感染占全球阴茎癌的 50%。扁平苔藓和硬化性苔藓在阴茎癌发生中的作用需要进一步研究。
对来自低发地区单一病理机构的存档福尔马林固定的高级别阴茎上皮内瘤变、分化的阴茎上皮内瘤变和浸润性癌进行了 28 种 HPV 低危和高危基因型、p16 过表达、肿瘤周围硬化性苔藓、扁平苔藓、前驱病变和 T 细胞受体 γ 基因座单克隆重排的分析。
共 29 例（100%）上皮内瘤变和 115 例（60%）浸润性癌中含有 HPV 高危型，单一 HPV 高危型（80%HPV16、6%HPV33、2%HPV45 和 HPV18、1%HPV73）。4%的病例存在多种 HPV 高危型，5%的病例无 HPV16/18。除 1 例 HPV45 高危癌症外，所有病例均存在 p16 过表达。在 6 例分化的阴茎上皮内瘤变和 115 例（40%）浸润性癌中未发现 p16 过表达和 HPV 基因型，其中 30%为 pT2/pT3 癌。35 例癌症有肿瘤周围组织可供分析。26 例存在晚期硬化性苔藓，9 例存在扁平苔藓，18 例存在分化的阴茎上皮内瘤变。46 例浸润性癌中有 22 例和 6 例分化的阴茎上皮内瘤变中有 3 例存在密集的以 T 细胞为主的淋巴细胞浸润，13 例分析的癌症/阴茎上皮内瘤变中有 6 例存在 T 细胞受体 γ 基因座的单克隆重排。
低发地区阴茎癌高危 HPV 的患病率略高于全球分布。HPV 阴性癌与晚期硬化性苔藓和扁平苔藓、分化的阴茎上皮内瘤变以及 T 细胞受体 γ 基因座单克隆重排的 T 淋巴细胞积聚有关。
