Objective

The global rise of HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) has generated considerable interest underlying its etiology and management. Relative to HPV(-) OPSCC, HPV(+) patients are younger and more responsive to chemoradiation, though non-responders within this sub-class of OPSCC indicate divergent molecular pathophysiology, and continue to challenge clinicians. Rather than an adaptive approach to what many consider distinct disease processes, treatment remain the same for all OPSCC. Improved molecular stratification would greatly enhance the clinician's ability to precisely tailor treatment without jeopardizing outcomes. Here, two HPV(+) OPSCC cohorts delineated based on treatment response are compared via a hybrid Data Dependent Acquisition/Data Independent Acquisition (DDA/DIA) approach via mass spectrometry, to detect low-abundance proteins and highlight pathways not detected through genomic platforms alone.