In this research study the investigators are examining a blood test to detect HPV DNA in the blood that can possibly detect cancer recurrence earlier than with standard surveillance measures.

This research study involves blood tests to detect HPV DNA at regular time points after treatment for HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPC). Participants may undergo scans based on the results of the blood tests. Study participants will also be asked to complete quality of life questionnaires periodically.

Participation in this study may last for up to 3 years. It is expected that about 150 people will take part in this research study.

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed incident or recurrent squamous cell carcinoma of the tonsil or base of tongue (oropharynx) - includes biopsy of any lymph node with clinical evidence of an oropharynx tumor (unknown primary carcinoma in an involved cervical neck lymph node is permitted if high-risk HPV testing is positive on the involved node)
• HPV-associated tumor as defined by one or more : positive p16 immunohistochemistry (>70%) OR in situ hybridization OR PCR-based methods
• Age 18 years or older
• Will undergo oropharyngeal cancer treatment with curative intent
• Ability to understand and the willingness to sign a written informed consent document.
• Baseline positive or detectable ctHPV DNA result in plasma OR detectable corresponding HPV DNA in tumor tissue prior to treatment

Exclusion Criteria:

• Distant metastatic disease (M1, AJCC 8th edition)

Individuals with HPV-positive oropharynx cancer undergoing curative-intent treatment.

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Data can be shared no earlier than 1 year following the date of publication

Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu Contact the Partners Innovations team at http://www.partners.org/innovation