p16+ oropharyngeal squamous cell carcinoma is radiosensitive and has better prognosis than p16-ve. However, the correlation between p16 reactivity and radiation toxicity profile in these patients has not been studied. Edmonton Symptom Assessment System (ESAS) is a generic patient reported symptom scale validated for patient reported outcome (PRO) assessments in head and neck cancer patients. We sought to review the ESAS and its psychometric properties in oropharyngeal cancer patients treated with concurrent chemoradiation (CCRT) stratified by their HPV status. To evaluate differences in magnitude and temporal trends in PRO before, during and after radiation treatments in both p16+ and p16-ve oropharyngeal cancer patients using ESAS scores. Prospectively collected ESAS scores for oropharyngeal cancer patients treated at a safety net hospital with CCRT were analyzed. Longitudinal variation in pain, depression, appetite and family distress scores before, during and up to 36 weeks after CCRT were evaluated at seven time points: prior to treatment, 1-3, 4-6, 7-10, 11-15, 16-20 and 20-36 weeks. Statistical analysis focused on data collected through repeated measurements for patients using ANOVA mixed regression analysis using p16 status as between subjects factor for each symptom. Three hundred fifty-five ESAS assessments were analyzed for each symptom for 64 oropharyngeal cancer patients treated with CCRT. Subsites identified were 21 (32.8%) tonsil, 15 (23.4%) base of tongue, 22 (34.4%) soft palate, and 6 (9.4%) oropharynx not specified. We identified 35 (54.7%) p16+ and 29 (45.3%) p16-ve patients. The median age of the cohort was 60 (range: min 39 - max 88); the median age was 59 for p16+ and 61 for p16-ve. Median total radiation dose was 6996 Gy. Pain scores peaked at 7-10 weeks for both groups but p16-ve had delayed peak 11-15 weeks as well. Depression scores stayed <4 for both populations but family distress, pain and appetite scores peaked for p16-ve between 11-15 weeks. Mean pain scores were similar for both populations and peak during CCRT for both however p16-ve patients have another peak after completion of CCRT. Family distress and decreased appetite also heighten during this post CCRT time for p16-ve patients which warrants a planned early intervention at 11-15 weeks for these patients to improve their quality of life.