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

Abstract

Background: Vulvar squamous cell carcinoma (VSCC) is subdivided into TP53-mutant (TP53^mut) and HPV-associated (HPV⁺). In recent years, a third group unrelated to TP53 mutation or HPV-association (TP53^wt/HPV^-) has emerged. However, its prognosis is unclear.

Objective: The aim of this study was to define the prognosis of TP53^wt/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 TP53^wt/HPV^- VSCC to that of TP53^mut 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 TP53^mut, 302 HPV⁺, 298 TP53^wt/HPV^-) were included in the meta-analysis. TP53^wt/HPV^- VSCC showed significantly better PFS (HR = 0.714; p = 0.022) and DSS (HR = 0.633; p = 0.037) than TP53^mut VSCC and significantly worse PFS (HR = 2.555; p = 0.001) and DSS (HR = 1.973; p = 0.024) than HPV⁺ VSCC.

Conclusions: TP53^wt/HPV^- VSCCs constitute a group at intermediate risk, with a prognosis significantly better than TP53^mut VSCC and significantly worse than HPV⁺ VSCC.

Keywords: Neoplasia; Prognosis; Squamous cell carcinoma; Survival; Vulva.