p16(INK4a) immunohistochemical expression is a strong predictor of treatment response and survival in patients with locally advanced squamous cell vulvar cancer undergoing upfront chemoradiotherapy

OBJECTIVE: To evaluate the prognostic significance of tumor p16(INK4a) expression in predicting treatment response and survival in patients with locally advanced squamous cell vulvar cancer (LAVC) undergoing chemoradiotherapy (CRT). METHODS: Retrospective data were collected from patients with stage II-IVB disease managed with definitive or neoadjuvant CRT between January 2016 and March 2024. Clinical response to CRT and survival outcomes according to tumor p16 expression were evaluated. RESULTS: Among 61 patients, 39 (63.9%) had p16-negative (p16-) tumors, 22 (36.1%) had p16-positive (p16+) tumors. p16 positivity was linked to higher complete clinical response (cCR) rates (odds ratio [OR]=9.8; p<0.001) and, after adjusting for tumor size, lymph node status and radiation dose, was the only independent predictor of cCR (OR=7.0; p=0.003). The 3-year progression-free survival (PFS), locoregional control (LRC), and overall survival (OS) rates were 12.6%, 17.3%, and 19.5% for p16- tumors, 60.4% (p<0.001), 80.4% (p<0.001), and 64.9% (p<0.001) for p16+ tumors. Among patients who achieved a cCR, the 3-year PFS, LRC and OS were 14.3%, 14.3%, and 33.3% for p16- tumors, 69.6% (p=0.001), 85.7% (p<0.001), and 80.2% (p=0.008) for p16+ tumors. p16 positivity was independently associated with improved PFS (hazard ratio [HR]=0.15, p<0.001), LRC (HR=0.09, p<0.001), and OS (HR=0.16, p<0.001). Larger tumor size adversely affected all outcomes, while age, lymph node status, and RT dose were not significant predictors. CONCLUSION: p16(INK4a) expression predicts treatment response, locoregional disease control and survival in LAVC undergoing upfront CRT. These findings highlight the importance of integrating p16 expression into treatment protocols and future clinical trials.