Prognosis of HPV-independent, p53-wild-type vulvar squamous cell carcinoma: A systematic review and meta-analysis

Background: Vulvar squamous cell carcinoma (VSCC) is subdivided into TP53-mutant (TP53mut) and HPV-associated (HPV+). In recent years, a third group unrelated to TP53 mutation or HPV-association (TP53wt/HPV−) has emerged. However, its prognosis is unclear. Objective: The aim of this study was to define the prognosis of TP53wt/HPV−VSCC through a systematic review and meta-analysis. Methods: Electronic databases were searched from their inception to February 2025 for studies comparing the prognosis of TP53wt/HPV− VSCC to that of TP53mut and HPV+ VSCC. Pooled hazard ratios (HR) for recurrence-free survival (RFS) and disease-specific survival (DSS) were calculated, with a significant p-value<0.05. Results: Six studies were included in the systematic review, while 5 studies with 1355 VSCCs (755 TP53mut, 302 HPV+, 298 TP53wt/HPV−) were included in the meta-analysis. TP53wt/HPV− VSCC showed significantly better PFS (HR = 0.714; p = 0.022) and DSS (HR = 0.633; p = 0.037) than TP53mut VSCC and significantly worse PFS (HR = 2.555; p = 0.001) and DSS (HR = 1.973; p = 0.024) than HPV+ VSCC. Conclusions: TP53wt/HPV− VSCCs constitute a group at intermediate risk, with a prognosis significantly better than TP53mut VSCC and significantly worse than HPV+ VSCC.