HPV-16 Vaccination and Pembrolizumab Plus Cisplatin for "Intermediate Risk" HPV-16-associated Head and Neck Squamous Cell Carcinoma

Inclusion Criteria: * Histologically-confirmed head and neck squamous cell carcinoma with no evidence of distant metastasis, with a primary site being the oropharynx. Squamous cell carcinoma of unknown primary, metastatic to cervical lymph nodes - patients can enroll provided all other eligibility criteria are met. * Patients must have intermediate risk disease. o Patients must meet one of the following criteria: Oropharynx: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following; ≥ AND ≥ 10 pack-years tobacco exposure (see Tobacco Assessment Form, Appendix A) * T4 or N2c/N3 disease irrespective of tobacco exposure * Unknown primary: p16(+) PLUS HPV ISH(+) (DNA or RNA) AND one of the following * ≥ N2a AND ≥ 10 pack-years tobacco exposure * N2c/N3 disease irrespective of tobacco exposure * Patients should be considered not a candidate for curative-intent surgery with diagnosis of AJCC 7th edition Stage III, IVa, or IVb disease. * Diagnostic simple palatine or lingual tonsillectomy is permitted, provided patient has RECIST-measurable nodal disease. * Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy or radiotherapy), and has not recurred. * Patients with simultaneous primaries are excluded, with the exception of patients with bilateral tonsil/base of tongue HPV+ cancers or patients with T1-2, N…