From the Division of Anatomical Pathology (Keller, Sekhon, Flood), Department of Pathology and Laboratory Medicine, The Ottawa Hospital/University of Ottawa, Ottawa, Ontario, Canada.
The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada (Pastukhova).
Arch Pathol Lab Med. 2023 Jun 1;147(6):722-734. doi: 10.5858/arpa.2021-0592-RA.
CONTEXT.—: Penile squamous cell carcinomas (PSCCs) are divided into tumors that are human papillomavirus (HPV) associated and those that are non-HPV associated. HPV and non-HPV PSCCs each display unique pathogenic mechanisms, histologic subtypes, and clinical behaviors. Treatment of localized PSCC tumors is linked to significant physical and psychological morbidity, and management of advanced disease is often treatment refractory. The identification of novel actionable mutations is of critical importance so that translational scientists and clinicians alike can pursue additional therapeutic options.
OBJECTIVE.—: To provide an update on the molecular pathogenesis associated with PSCC. A special emphasis is placed on next-generation sequencing data and its role in identifying potential therapeutic targets.
DATA SOURCES.—: A literature review using the PubMed search engine to access peer-reviewed literature published on PSCC.
CONCLUSIONS.—: Our understanding of the genetic and molecular mechanisms that underlie PSCC pathogenesis continues to evolve. PSCC tumorigenesis is mediated by multiple pathways, and mutations of oncogenic significance have been identified that may represent targets for personalized therapy. Preliminary results of treatment with immune checkpoint inhibition and tyrosine kinase inhibitors have produced variable clinical results. Further insight into the pathogenesis of PSCC will help guide clinical trials and develop additional precision medicine approaches.
阴茎鳞状细胞癌（PSCC）可分为人乳头瘤病毒（HPV）相关肿瘤和非 HPV 相关肿瘤。HPV 和非 HPV PSCC 各具有独特的发病机制、组织学亚型和临床行为。局部 PSCC 肿瘤的治疗与显著的身体和心理发病率有关，晚期疾病的治疗往往具有难治性。鉴定新的可操作突变至关重要，以便转化科学家和临床医生都可以寻求更多的治疗选择。
提供与 PSCC 相关的分子发病机制的最新信息。特别强调下一代测序数据及其在识别潜在治疗靶点中的作用。
使用 PubMed 搜索引擎进行文献复习，获取已发表的关于 PSCC 的同行评议文献。
我们对 PSCC 发病机制的遗传和分子机制的理解仍在不断发展。PSCC 肿瘤发生是由多种途径介导的，已经确定了具有致癌意义的突变，这些突变可能代表个性化治疗的靶点。免疫检查点抑制和酪氨酸激酶抑制剂治疗的初步结果产生了不同的临床结果。进一步深入了解 PSCC 的发病机制将有助于指导临床试验和开发更多的精准医疗方法。
