This study is for patients diagnosed with recurrent/persistent PD-LI enriched squamous cell carcinoma of the head and neck and undergoing salvage surgery. The purpose of this study is to compare the usual treatment of surgery alone, to using chemotherapy (cisplatin and paclitaxel) or chemo-immunotherapy [carboplatin and paclitaxel with cemiplimab (REGN2810)] plus the usual treatment.

Carboplatin, cisplatin, paclitaxel, and cemiplimab are FDA approved to treat head and neck cancers. This study seeks to answer if adding chemotherapy or chemo-immunotherapy before surgery extends the length of time without your cancer returning compared to the surgery alone.

Patients may participate in this study for up to 3 years. Procedures surgery, blood tests, chemotherapy, and regular visits with your doctor including follow-up study visits or phone calls every 3 months. There will be about 180 people taking part in this study, approximately x participants will be enrolled at MUSC.

Risks include hair loss, diarrhea, nausea, vomiting, anemia, infection, and fever. Participants may or may not receive a direct benefit from participating in this trial, however, information learned from the trial may help other people in the future.