Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations inTP53, but recently, attention has focused on the uncommonTP53wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers forTP53mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC withTP53mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-typeTP53(p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors.
外阴癌是一种罕见疾病，符合“罕见癌症”标准，但其发病率正在上升，尤其是在60岁以下女性中。鳞状细胞癌（VSCC）占外阴癌的绝大多数，是本综述的重点。与许多癌症一样，对肿瘤发生过程中分子事件的深入理解导致了VSCC分子亚分类的出现，其可分为继发于高危人乳头瘤病毒感染（HPV相关，或HPVa）的肿瘤和独立于HPV发生的肿瘤（HPVi），后者最常见于外阴皮肤慢性炎症状态。这组HPVi VSCC在大多数情况下继发于TP53突变，但最近，关注点集中在罕见的TP53野生型HPVi VSCC上。VSCC的这三种分子亚型（HPVa、HPVi p53异常和HPVi p53野生型）及其前驱病变无法仅基于常规组织病理学检查进行诊断，需要分别使用p53和p16免疫染色作为TP53突变和高危HPV感染的替代标志物。VSCC的分子分型显示出高度的可重复性，并提供重要的预后信息。HPVa VSCC预后最好，而伴有TP53突变（p53abn）的HPVi VSCC预后最差，伴有野生型TP53（p53wt）的HPVi VSCC预后居中。在本综述中，我们讨论了支持这种分子亚分类的证据及其对VSCC及其前驱病变诊断和治疗的意义。
肿瘤(癌症)患者之家