The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing and effective treatment for targeting the subset of patients at high risk for recurrence remains a significant clinical challenge. In this study, pre-treatment tumour biopsies were used for proteomic analysis by data-independent acquisition mass spectrometry (DIA-MS) to identify protein and peptide biomarker signatures able to stratify patients at low, intermediate, or high-risk of recurrence. For further details, refer to the publication that accompanies this data deposition.