Einstein Montefiore

All Patients: - Documentation of confirmed HPV 16+ cancer via genotype testing. - ≥ 1 measurable lesion by imaging for tumor response following RECIST - ECOG performance status of 0 to 1. - Prior curative radiation therapy and prior focal palliative completed per protocol-specified wash-out windows. - Screening laboratory values must meet protocol-specified criteria. Treatment Group 1, Group 3, Group A, or Group D: - Documentation of confirmed head and neck squamous cell carcinoma. - Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy. - Able to provide tumor tissue following last treatment, unless otherwise agreed. Treatment Group 2, Group 4, Group C, or Group F: - Tumor progression or recurrence on standard of care therapy, including ≥ 1 systemic therapy. - Safe and accessible tumor site amenable for biopsy and intratumoral administration. - Apart from the tumor site(s) amenable for biopsy and IT administration, ≥ 1 measurable lesion for RECIST assessment. Treatment Group B or Group E: - Documentation of confirmed head and neck squamous cell carcinoma. - Eligible, per standard of care, to receive immune checkpoint inhibitor. - Able to provide tumor tissue following last treatment, unless otherwise agreed.

All patients: - Untreated and/or symptomatic metastatic central nervous system disease, unless protocol-defined criteria is met. - Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation / treatment administration. - Concurrent malignancy that is clinically significant or requires active intervention, unless protocol-defined criteria is met. - Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy. - Any toxicities attributed to systemic prior anticancer therapy o that have not resolved to Grade 1 or baseline prior to the first administration of study drug, unless protocol-defined criteria is met. - Not meeting the protocol-specified washout periods for prohibited medications. - Prior anaphylactic or other severe reaction to human immunoglobulin or antibody formulation administration. - Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, indicating acute or chronic infection. - Known history of acquired immunodeficiency syndrome. For patients in Groups B or E • History of severe hypersensitivity reaction to or other contraindication to receiving immune checkpoint inhibitor.