Inclusion Criteria:
Subject must meet all of the following applicable inclusion criteria to participate in this study:
1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Histologically or cytologically confirmed squamous cell carcinoma from oropharynx. note: patients with a clinical diagnosis of oropharyngeal cancer, awaiting a biopsy is eligible to consent for prescreening.
3. Stage I-III per AJCC 8th edition
4. Positive p16 immunohistochemistry or HPV testing, or p16/HPV status unknown with patients having a less than 10 pack-year smoking history
5. Age ≥ 18 years at the time of consent.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 for patients who receive treatment
7. Persistent detection of cfDNA HPV (≥ 16 copies/mL) in the absence of clinically evident disease at 3, 6, or 9 months following definitive treatment (surgery, systemic therapy, and/or radiation therapy).
8. Patients must have adequate hematologic, coagulation, hepatic, and renal function for anti-PD1 treatment. this includes:
* ANC \>/= 1,500/mm3
* platelet count \>/=100,000/mm3
* HgB ≥ 9 g/dL (may be with transfusion)
* Creatinine ≤ 1.5x ULN or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).
* Total Serum Bilirubin ≤ 1.5 x ULN (Patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
* SGOT, SGPT ≤ 3 X ULN
* SGOT, SGPT ≤ 5 X ULN
9. Females of childbearing potential must not be breast feeding and must have a negative pregnancy test during screening and 7 days prior to initiation of study treatment. The patient must agree to use adequate contraception. Note: women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following agespecific requirements must also apply: women \< 50 years old: they would be considered postmenopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as per the institution). Women ≥ 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses \> 1 year ago, or have had chemotherapyinduced menopause with \>1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy.
10. Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study.
Exclusion Criteria:
Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
1. Prior treatment history with anti-PD-1 or anti-PD-L1 therapies are not allowed.
2. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol, or active and uncontrolled infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
Screening for chronic conditions is not required.
3. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirement.
4. Active rheumatological or autoimmune conditions requiring systemic treatment, such as steroids.
5. Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids.
