Background: Blockade of the PD-1/PD-L1 immune checkpoint improves survival in recurrent/metastatic head and neck cancer. PD-L1 expression is a biomarker that enriches for clinical benefit with anti-PD-1 therapy alone or in combination with chemotherapy in this setting. The role of PD-L1 expression as a predictive biomarker in locoregional human papillomavirus associated (HPV+) head and neck cancer (HNC) treated with induction nivolumab-based chemoimmunotherapy is unknown. We evaluate PD-L1 expression and response to induction chemoimmunotherapy in the context of an investigator initiated trial, OPTIMA II. Methods: Patients with locoregionally advanced HPV+ HNC were enrolled to the prospective OPTIMA II study evaluating induction chemoimmunotherapy followed by response adaptive de-escalated locoregional therapy. Induction therapy consisted of nivolumab, nab-paclitaxel, and carboplatin, for three cycles. Anatomic imaging of the head and neck with either CT or MRI was obtained at baseline and following induction therapy. Expression of PD-L1 was assessed by immunohistochemistry on baseline biopsies and calculation of tumor proportion score (TPS) and combined positive score (CPS) was performed. Response is defined as percentage of tumor shrinkage per RECIST 1.1 criteria. Deep response rate is defined as the proportion of patients with > = 50% tumor shrinkage. Kruskal-Wallis and Mann-Whitney tests were used for analysis. Results: Twenty-nine patients (pts) underwent evaluation of PD-L1 expression and started treatment with induction chemoimmunotherapy. Median age 61 (range 37-81), smoker > 20 pack years in 24%, tonsil primary in 79%, and HPV16 subtype in 97%. The median response following induction was 63% (range 29% to 100%). PD-L1 TPS scores were < 1, 1-19, and > = 20 in 28%, 34%, and 38% respectively. PD-L1 CPS scores were < 20 and > = 20 in 55% and 45% respectively. Median response among PD-L1 TPS of < 1, 1-19, and > = 20 was 49%, 59%, and 66% respectively (p = 0.16). Among PD-L1 CPS of < 20 and > = 20, median response was 57% and 69% respectively (p = 0.11). The deep response rate among PD-L1 CPS < 20 and > = 20 was 69% and 77% respectively. Conclusions: Deep responses were observed following induction chemoimmunotherapy in locoregionally advanced HPV+ HNC. There was a non-significant increase in median response and deep response rate with higher expression of PD-L1. Evaluation of PD-L1 expression as a biomarker for response with induction chemoimmunotherapy is worthy of further investigation in locoregional HPV+ disease. Clinical trial information: NCT03107182.