Inclusion Criteria:
* Age ≥ 18 years
* Able to provide written consent
* Groups 1-3:
* Must undergo p16 staining on biopsy for enrollment
* Patients with \< 70% of tumor cells positive for p16 will be considered p16 negative
* Must undergo HPV16 family in situ hybridization (ISH) and/or RNA on biopsy or surgical specimen, unless amount of tissue is too small to have conclusive HPV ISH testing done on it
* Willingness and intent to return in person to enrolling institution for follow-up (during the Active Monitoring Phase of the study) for at least 2 of the standard follow-up time points for a total of 3 time-points including pre-treatment. A participant who does not return in person to Mayo Clinic Rochester for every standard of care post-treatment follow up will not be considered deviating from the protocol
* Group 4:
* Clinical suspicion or histopathologic diagnosis of head and neck cancer or neoplasm
* Primary salivary neoplasm
* Primary thyroid neoplasm
* Primary head and neck neoplasm
* Multi-cancer early detection (MCED) testing concerning for cancer
* Patient has given permission to give his/her tumor/tissue/blood/saliva sample for research testing
* Ability to complete questionnaire(s) by themselves or with assistance
* Primary language: English, Spanish, Arabic
Exclusion Criteria:
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
* Groups 1-3:
* Other active malignancy ≤ 5 years prior to registration
* EXCEPTIONS: Non-melanotic skin cancer, non-metastatic thyroid cancer, non-metastatic prostate cancer, carcinoma-in-situ of the cervix, HPV+ oropharyngeal squamous cell carcinoma (SCC) (which can be enrolled in group 3)
* NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
* History of any head and neck malignancy, other than the tumor for which they are being treated
* Group 4, Cohort A, B, C:
* Other active malignancy ≤ 5 years prior to registration
* EXCEPTIONS: Non-metastatic prostate cancer, carcinoma-in-situ of the cervix, non metastatic cutaneous basal cell carcinoma
* NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
* History of any head and neck malignancy, other than the present neoplasm
* Note these are clarifications of inclusion into Group 4, Cohorts D and E:
* Presence of other active malignancy or recurrent head and neck neoplasms are allowed in this arm
* Receipt of cancer specific therapy for other malignancy is allowed in this arm