- Previously untreated, histologically proven, surgically resectable primary squamous cell carinoma of the head and neck, stage III or IV (HPV positive or negative non-metastatic disease). SCCHN of unknown primary is excluded. SCCHN of the oral cavity is allowed*. Unambiguously squamous Epstein-Barr virus (EBV)-negative nasopharynx cancer will be excluded nor will unambiguously squamous cancers of the skull base that are clearly surgically resectable and clearly squamous. Squamous skin cancer occurring in the head/neck region will not be eligible nor will EBV+positive nasopharynx cancer. (*Note: Induction chemotherapy is not considered standard therapy for SCCHN of the oral cavity and participation on this trial will lead to a delay in time to definitive, potentially curative therapy i.e., surgery).