Cell-Free Tumor DNA Testing for Deciding When to Start Routine Treatment in Patients with Human Papillomavirus-Associated Oropharynx Cancer

Inclusion Criteria

• Age >= 18
• Eastern Cooperative Oncology Group (ECOG) 0-2
• HPV-16 squamous cell carcinoma of the oropharynx or HPV-16 head and neck squamous cell carcinoma of unknown primary. HPV status must be confirmed by in-situ hybridization
• HPV ctDNA detectable by HPV digital polymerase chain reaction (PCR) (Naveris assay) with a minimum of 50 copies/mL pre-operatively
• Surgical resection of all gross disease with no gross disease visualized on post-operative imaging. * For patients with pT0 (unknown primary) evaluation for the primary should include PET/CT, direct laryngoscopy, ipsilateral tonsillectomy, and targeted biopsy. This should be followed by a neck dissection
• Two, undetectable (< 1 copy/mL) post-operative HPV ctDNA within 2-8 weeks following surgery (blood drawn at least one week apart preferred)
• COHORT A: A minimum of one of the following pathologic criteria: * American Joint Committee on Cancer (AJCC) 7 Stage: pT0N1-N2b, pT1N1, pT2N1, or >= pT3 * AJCC 7 >= pN2 * Lymphovascular invasion * Perineural invasion * Close pathologic margin (=< 3 mm)
• COHORT B: A minimum of one of the following pathologic criteria: * Microscopic positive margin * Extracapsular extension
• Signed informed consent form by the participant or their legally authorized representative (LAR)
• COHORT B: White blood count (WBC) >= 2 K/mcL (within 30 days prior to registration)
• COHORT B: Absolute neutrophil count (ANC) >= 1,000 cells/mm^3 (within 30 days prior to registration)
• COHORT B: Platelets >= 100,000 cells/mm^3 (within 30 days prior to registration)
• COHORT B: Hemoglobin >= 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb >= 8.0 g/dl is acceptable (within 30 days prior to registration)
• COHORT B: Adequate renal function within 30 days prior to registration, defined as follows: * Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula: ** CCr male = [(140 – age) x (wt in kg)] divided by [(Serum Cr mg/dl) x (72)] ** CCr female = 0.85 x (CrCl male)
• COHORT B: Adequate hepatic function within 30 days prior to registration, defined as follows: * Bilirubin < 2 mg/dl * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the upper limit of normal
• COHORT B: Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential

Exclusion Criteria

• Metastatic disease
• Non-HPV16 genotype (i.e. HPV-18,-31, -33, -35)
• Patients who receive surgery at outside institution. Exceptions can be made for high-volume surgical centers at the discretion of the principal investigator (PI) or co-PI
• Prior head and neck radiation
• Patients without pre-operative HPV ctDNA or pre-operative HPV ctDNA =< 50 copies/mL
• Subjects with simultaneous primary cancers outside of the oropharynx * Note: Exceptions can be made for patients with simultaneous primaries outside of the oropharynx if determined by the PI/Co-PI, then the patient can proceed with protocol activities
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years is 90% or greater *Note: Exceptions can be made for patients with prior invasive malignancy if determined by the PI/Co-PI, then the patient can proceed with protocol activities
• Prior systemic chemotherapy for the study cancer * Note: prior chemotherapy for a different cancer is allowable
• Severe, active co-morbidity defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Lack of ability to understand and willingness to sign a written informed consent and complete questionnaires