Purpose To evaluate HPV and p16 ink4a status as prognostic factors in patients with invasive vulvar cancer. Methods Retrospective analysis of disease-free (DFS) and disease-specific survival (DSS) of patients with invasive vulvar cancer at a single tertiary care center. Histology, HPV and p16 ink4a status were evaluated in the context of a global multicenter trial. Logistic regression models were performed to identify the impact of p16 ink4a positivity. Results 135 patients were included in the analysis. 32 (23.7%) showed a p16 ink4a expression of over 25%. Disease-free and disease-specific survival was longer in p16 ink4a positive patients (23 vs. 10 months, p = 0.004, respectively, 29 vs. 21 months, p = 0.016). In multivariate analysis, p16 ink4a positivity was an independent parameter for DFS (p = 0.025, HR: 2.120 (1.100-4.085)), but not for DSS (p = 0.926, HR: 1.029 (0.558-1.901), in contrast to age and tumor stage. Conclusions Age and tumor stage negatively affect survival. However, disease-free survival is significantly longer in patients with p16 ink4a positive invasive vulvar cancer.