Background: Development of squamous cell cancer of head and neck (SCCHN) is associated with humanpapillomavirus (HPV) infection, which in turn is closely related with expression of p16 INK4A. Loss of p16 INK4Aexpression by deletion, mutation, or hypermethylation is common in SCCHN. We here evaluated p16 INK4A as aprognostic marker of treatment response and survival in our SCCHN patients with laryngeal, hypopharyngeal ornasopharyngeal cancers. Materials and Methods: 131 patients diagnosed with SCCHN between January 2,2006and July 17, 2010 were examined for p16 INK4A. The median age was 60 years (15-82 years). Fifty one patients werestage I-II and 80 were stage III-IV. Immunohistochemical expression of p16 INK4A was analyzed in pretreatmentparaffin-embedded tumor blocks. The influence of p16 INK4A status on disease-free survival, and overall survivalafter treatment was evaluated. Results: P16 INK4A positivity was found in 58 patients (44%). Tumor-positivity forp16 INK4A was correlated with improved disease free survival (70.1 months vs 59 months) and improved overallsurvival (2, 3 and 5-year values; 77% vs 72%, 70% vs 63% and, 63% vs 55%; respectively). On multivariateanalysis, stage was determined as independent prognostic factor for disease-free survival. Conclusions: Stagewas the major prognostic factor on treatment response and survival in our patients. P16 INK4A status predictsbetter outcome in laryngeal, hypopharyngeal or nasopharyngeal cancer cases treated with surgery plus adjuvantradiochemotherapy as well as with definitive radiation therapy and/or chemotherapy.