Oropharynx (OPX) Biomarker Trial

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