Background: Advanced and recurrent vulvar squamous cell carcinoma (VSCC) presents a major therapeutic challenge with limited treatment options and poor outcomes. Immune checkpoint inhibitors (ICIs) have shown efficacy in other HPV-associated malignancies, but their role in VSCC remains poorly defined due to the rarity of the disease and limited clinical trial data.Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines and registered in PROSPERO (CRD420251067565). A comprehensive literature search identified prospective clinical trials evaluating ICIs in patients with advanced, unresectable, recurrent, or metastatic VSCC. The primary outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Risk of bias was assessed using the MINORS tool. Meta-analyses were performed using random-effects models, with subgroup analyses based on PD-L1 status and treatment regimens (monotherapy vs. combination therapy).Results: Six non-randomized single-arm trials involving 181 patients were included. The pooled ORR was 21%, with higher response rates observed in combination therapy (46%) compared to monotherapy (11%), though not statistically significant. Median PFS and OS were 2.2 months and 6.4 months, respectively. ORRs were similar between PD-L1-positive and PD-L1-negative subgroups. A safety analysis showed treatment-related adverse events (AEs) in 73% of patients and grade ≥ 3 AEs in 23%. The incidence of treatment-related death was 3%.Conclusions: ICIs demonstrate modest but durable efficacy and an acceptable safety profile in advanced VSCC. The current evidence supports their use in selected patients. However, response variability and the lack of reliable predictive biomarkers, such as PD-L1 or HPV status, underscore the need for biomarker-driven clinical trials and improved patient selection strategies.
背景：晚期及复发性外阴鳞状细胞癌（VSCC）因治疗选择有限且预后不良，构成重大临床挑战。免疫检查点抑制剂（ICIs）在其他HPV相关恶性肿瘤中已显示疗效，但由于该疾病罕见且临床试验数据有限，其在VSCC中的作用仍不明确。 方法：本研究遵循PRISMA指南进行系统综述与荟萃分析，并在PROSPERO平台注册（CRD420251067565）。通过全面文献检索，纳入评估ICIs治疗晚期、不可切除、复发性或转移性VSCC患者的前瞻性临床试验。主要结局指标包括客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）及安全性。采用MINORS工具评估偏倚风险，使用随机效应模型进行荟萃分析，并基于PD-L1状态和治疗方案（单药治疗 vs 联合治疗）进行亚组分析。 结果：共纳入6项非随机单臂试验，涉及181例患者。汇总ORR为21%，联合治疗组缓解率（46%）高于单药治疗组（11%），但无统计学显著性。中位PFS和OS分别为2.2个月和6.4个月。PD-L1阳性与阴性亚组的ORR相似。安全性分析显示73%患者发生治疗相关不良事件（AEs），≥3级AEs发生率为23%，治疗相关死亡率为3%。 结论：ICIs在晚期VSCC中显示出适度但持久的疗效及可接受的安全性。现有证据支持其在特定患者中的应用。然而，治疗反应的异质性以及缺乏PD-L1或HPV状态等可靠预测生物标志物，凸显了开展生物标志物驱动临床试验和完善患者筛选策略的必要性。
肿瘤(癌症)患者之家