Inclusion Criteria:

          -  Males and females, ≥ 18 years of age.

          -  Sign and date an Institutional Review Board/Independent Ethics Committee
             (IRB)/(IEC)-approved written informed consent form (ICF) in accordance with regulatory
             and institutional guidelines. This must be obtained before the performance of any
             protocol-related procedures that are not part of normal subject care.

          -  Be willing and able to comply with scheduled visits, treatment schedule, laboratory
             testing, and other requirements of the study.

          -  Diagnosed with histologically confirmed recurrent or metastatic HPV16 positive OPC,
             whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) and who are candidates
             for first line therapy with an PD-1 blocking antibody, AND subjects with recurrent or
             metastatic HPV16 positive OPC with disease progression on or after platinum containing
             chemotherapy.

          -  HPV-16 genotyping will be determined by the specified central reference laboratory.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          -  Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per
             RECIST 1.1 criteria.

          -  Prior curative radiation therapy must have been completed at least 4 weeks prior to
             study drug administration. Prior focal palliative radiotherapy must have been
             completed at least 2 weeks before study drug administration.

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
             [HCG]) within 24 hours prior to the start of study drug.

        Exclusion criteria:

          -  Subjects with previously untreated metastatic or unresectable, recurrent HPV16
             positive OPC whose tumors do not express PD-L1 (CPS<1) and who are therefore not
             candidates for monotherapy with an anti-PD-1 antibody.

          -  Subjects with known brain metastases or leptomeningeal metastases.

          -  Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
             may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy, or
             interfere with the interpretation of study results.

          -  History of other malignancy ≤ 3 years prior to entry into this trial with the
             exception of basal cell or squamous cell skin carcinoma which were treated with local
             resection only, or carcinoma in situ of the cervix, prostate or breast, or low grade
             non-muscle invasive superficial bladder cancer (TaLG)/carcinoma in situ of the
             bladder.

          -  Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
             type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
             requiring hormone replacement, psoriasis not requiring systemic treatment, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll.

          -  Subjects with a condition requiring immunosuppressive doses of systemic medication
             such as steroids or absorbed topical steroids (doses ≥ 10 mg/day prednisone or
             equivalent) or other immunosuppressive medications within 14 days of study drug
             administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg
             daily prednisone equivalents are permitted in the absence of active autoimmune
             disease.

          -  Prior treatment with an anti-PD-1 antibody (e.g., nivolumab, pembrolizumab,
             cemiplimab), as well as an antibody targeting anti-PL-L1 anti-PD-L2, anti-CTLA-4
             antibody, or any other antibody or drug specifically targeting T-cell co stimulation
             or immune checkpoint pathways.

          -  Prior treatment with more than one chemotherapy regimen for the management of
             metastatic OPC.

          -  Prior treatment with therapeutic anti-HPV vaccines including ISA101 or ISA101b.
             Subjects may have received a preventive HPV vaccine.

          -  All toxicities attributed to systemic prior anti-cancer therapy other than alopecia
             and fatigue must have resolved to Grade 1 (NCI CTCAE) or baseline before
             administration of study drug. Subjects with toxicities attributed to systemic prior
             anticancer therapy that are not expected to resolve and result in long lasting
             sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.

          -  History of allergy to ISA101/ISA101b study drug components, e.g., ISA101/101b,
             Montanide, or Macrogolglycerol Ricinoleate, also known as cremophore.

          -  History of allergy to cemiplimab and its excipients.