Background: Despite the survival benefit of anti-PD1 therapy in recurrent/metastatic head and neck cancer, its role in locoregional disease remains undefined. Swallowing and quality of life (QoL) outcomes for patients with human papillomavirus associated (HPV+) oropharyngeal cancer (OPC) treated with de-intensified local therapy following anti-PD1 based induction is unknown. Here we report functional swallowing and QoL outcomes with response-adaptive de-escalation after induction chemoimmunotherapy in the context of a prospective investigator initiated trial, OPTIMA II. Methods: OPTIMA II enrolled locoregionally advanced HPV+ OPC. Treatment consisted of induction therapy with 3 cycles of nivolumab, nab-paclitaxel, and carboplatin, followed by risk and response de-escalated local therapy. High-risk (HR) included: T4, N2c-N3 (AJCC 7th edition), > 20 pack year smoking history, or non-HPV16 subtype; All others were low-risk (LR). Single-modality de-escalation received radiation (RT) alone to 50 Gy or transoral robotic surgery, and was administered to LR with ≥50% post-induction shrinkage by RECIST. Intermediate-dose de-escalation received chemoradiation (CRT) to 45-50Gy and was administered to HR with ≥50% shrinkage or LR with < 50% shrinkage. All others received regular-dose CRT to 70-75 Gy. Adjuvant nivolumab was administered for 6 months. Swallowing and QoL was assessed with the Rosenbek score and EORTC QLQ-C30 questionnaires, respectively. Higher values indicated greater degree of swallowing dysfunction and worse QoL, respectively. Results: Seventy-three eligible patients (pts) initiated treatment on protocol. Median age 61 (range 37-82). Primary site was tonsil in 70% and base of tongue in 29%. T3 or T4 primary tumor in 30%. De-escalated therapy was administered in 62 pts, of which 28 pts received single-modality and 34 pts received intermediate-dose. Rosenbek mean and standard deviation (SD) at baseline among single-modality, intermediate-dose, and regular-dose, was 1.3 (SD 0.6), 1.7 (SD 1.3), and 1.4 (SD 0.7), respectively. Rosenbek mean at 1 month following local therapy (n = 45) among single-modality, intermediate-dose, and regular-dose was 2.3 (SD 1.6), 3.8 (SD 2.5), and 4.7 (SD 2.1), respectively (p = 0.06). Feeding tube rates at the end of local therapy among single-modality, intermediate-dose, and regular-dose was 7%, 44%, and 75% respectively (p < 0.01). QoL scores (n = 30) were worse among regular-dose as compared with de-escalated treatment for activities of daily living (p = 0.01), neuropathy (p = 0.01), and eating in social settings (p = 0.09). Conclusions: Response adaptive de-escalated treatment for HPV+ OPC following nivolumab/nab-paclitaxel/carboplatin induction is associated with improved swallowing function, reduced rates of enteral feeding, and an improvement in QoL across several domains. Clinical trial information: NCT03107182.