Inclusion Criteria:

          -  Participants must meet the following eligibility criteria at the time of screening to
             be eligible to participate in the study:

          -  Subject must have histologically or cytologically confirmed, stage I, II, or III, HPV
             associated oropharyngeal (tongue base or tonsil) squamous cell carcinoma, as defined
             by 2017 American Joint Committee on Cancer (AJCC), 8th edition staging.

             -- Patients with HPV-associated disease of unknown primary (cT0) are eligible

          -  HPV status should be confirmed on tissue biopsy or cytologic sample by any of the
             following:

               -  Immunohistochemical staining for p16 with ≥70% expression

               -  Confirmatory DNA testing (PCR or ISH) for high-risk subtype

          -  Willing to provide blood and tissue from a diagnostic biopsy and blood samples before,
             during, and after treatment.

          -  Detectable HPV ctDNA blood sample at baseline, prior to treatment, using the NavDx®
             assay that detects HPV subtype 16

          -  Age 22 years or older

          -  ECOG performance status ≤ 2

          -  Participants should have adequate organ and marrow function if they are to receive
             chemotherapy (cisplatin, or carboplatin and paclitaxel) with radiation concurrently as
             determined by standard institutional guidelines and investigator preference
             (parameters suggested below).

               -  absolute neutrophil count (ANC) ≥ 1000

               -  platelet count ≥ 100,000

               -  total bilirubin of 1.5 or less

               -  creatinine of 1.6 or less (or a CrCl ≥50 mL/min) per institutional standards.

          -  Planning to receive non-surgical management for HPV+ oropharyngeal cancer

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the
             start of (chemo)radiation therapy. "Women of childbearing potential (WOCBP)" is
             defined as any female who has experienced menarche and who has not undergone surgical
             sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
             Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the
             absence of other biological or physiological causes. In addition, women under the age
             of 55 must have a documented serum follicle stimulating hormone (FSH) level above 40
             mIU/mL.

          -  Men who are sexually active with WOCBP must agree to use any contraceptive method with
             a failure rate of less than 1% per year. Men who are sexually active with WOCBP will
             be instructed to adhere to contraception for a period of 1 month after treatment.
             Women who are not of childbearing potential (i.e., who are postmenopausal or
             surgically sterile as well as azoospermic men) do not require contraception.

        Exclusion Criteria:

          -  Patients with AJCC 2017 8th edition stage IVC (metastatic) disease.

          -  Subject who has had prior radiation and/or chemotherapy for head and neck cancer.

          -  Any history of surgical resection (transoral robotic surgery, TORS) or surgical neck
             management prior to undergoing definitive RT or chemoradiation. Note: prior
             tonsillectomy as part of identification of the primary tumor site or biopsy is
             acceptable. Patients with HPV-associated unknown primary should not have undergone a
             neck dissection to be eligible.

          -  Undetectable baseline HPV ctDNA result by NavDx® testing or detectable baseline HPV
             ctDNA result for subtypes 18, 31, 33, or 35.

          -  Pregnant or lactating women.

          -  Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer, and
             low risk prostate adenocarcinoma being managed with active surveillance. A history of
             another separate malignancy in remission without evidence of active disease in the
             last 2 years is permitted.