The purpose of this research study is to see if it is possible to collect tissue, saliva and blood samples from patients who are having surgery and send those samples to different labs across MUSC. The researchers in these labs will collect tissue, blood and saliva samples before surgery and during surgery to see if there are any changes in the samples. They will compare the changes in the samples to the clinical outcomes. Patients will also be given surveys to evaluate patient preferences, anxiety/distress, symptom severity, support by HPV status.

The primary objective of this exploratory, proof of concept study is to facilitate translational science spanning clinicians and basic scientists to obtain tissue samples, PDX models, and clinical data in order to successfully analyze tissue linked to clinical outcomes in head and neck cancer, resulting in the methodological and statistical framework for a larger scale clinical trial in the future. While the incidence of HNSCC has been steadily decreasing over the last thirty years, the incidence and prevalence of oropharyngeal cancer squamous cell carcinoma (OPSCC) and young patients with oral tongue cancer has increased in the face of an overall decline in smoking prevalence. Over the past few years, evidence has emerged that oropharyngeal cancer is rising in incidence so rapidly that it has been described as an "epidemic" and that it has or soon will surpass cervical cancer in both incidence and mortality. In fact, over 30,000 patients will be diagnosed with oropharyngeal cancer in the US per year, making it the most rapidly rising head and neck cancer in incidence. Despite this unique etiopathogenesis, treatment and toxicities related to treatment have not changed. This collaboration and interdisciplinary study will be the first of its kind to address these important issues of cancer site, HPV status, tobacco history, gender, age, and race using both patient tissue and PDX models to identify novel and unique biomarkers. Also, innate to this project is the link between five separate laboratories each conducting unique biomarker analysis.

Inclusion criteria:

1. Age > 18 years
2. Ability to sign informed consent
3. Newly diagnosed or recurrent oral cavity squamous cell carcinoma of the tongue (stage I-IVa) or oropharyngeal squamous cell carcinoma confirmed by pathology report. Patients with Unknown primary of the neck that is HPV+ are eligible.
4. Planning to undergo surgery as a part of definitive treatment

Exclusion criteria:

1. Squamous cell carcinoma metastasis to node(s) of neck with unknown primary tumor site that is HPV negative.
2. Already received some treatment, such as chemotherapy, radiation, or surgery for his/her disease at another institution when presenting to MUSC. An exception is neoadjuvant PD-1 blockade.
3. History of radiation therapy, for any indication, to the head and neck region