The goal of this project is to describe somatic mutations of healthy oral mucosa from patients with oral squamous cell carcinoma (OSCC).

Epidermoid carcinomas of upper aerodigestive tract are the 8th most common cancers in the world. Worldwide, this represents more than 500.000 cases per year and 20.000 cases per year in France (statistics 2018-2020). Among these cancers, oral squamous cell carcinoma (OSCC) are the most common location, leading to significant morbidity and mortality.

Despite recent advances in diagnosis, treatment and monitoring, the overall 5-year survival rate of patients with epidermoid carcinomas of upper aerodigestive tract has not improved significantly and remains around 40-50 % for all combined locations. These pejorative survival rates, as well as the increase in the incidence of these cancers, have not changed much over the past 30 years. This situation can be attributed in part to a diagnosis too late. Indeed, only 1/3 of patients with high-risk squamous cell carcinoma of the head and neck are diagnosed at an early stage. This issue of early diagnosis is mainly due to the lack of suitable screening and diagnostic biomarkers. Beyond diagnosis, the identification of biomarkers is also a prognostic and predictive interest since they could predict the course of the disease as well as the response to treatment.

"Drivers" mutations, with oncogenic potential, can be present from the very early stages of epidermoid carcinomas of upper aerodigestive tract and therefore constitute potential biomarkers. However, recent studies have demonstrated the presence of driver mutations in different types of oral cavity's healthy tissue, some being even associated with a protective effect against tumor initiation. In order to improve prevention and early diagnosis of OSCC, it is important to better understand the evolutionary dynamics of somatic mutations in the oral mucosa, which is still poorly characterized.

Inclusion Criteria:

• I1. Male or female aged 18 years or older at the date of signature of the informed consent to participate.
• I2. Patient with histological diagnosis of epidermoid carcinomas of the oral cavity NB: All grades are eligible.
• I3. Patient naive of any systemic anti-cancer treatment (radio- or chemotherapy).
• I4. Patient able to understand, sign and date informed consent before the start of any study protocol procedure.
• I5. Patient affiliated or covered by a medical insurance

Exclusion Criteria:

• E1. Patients at high risk of bleeding, such as those on anticoagulant or antiplatelet aggregant treatment, with clotting disorders or a history of severe bleeding in the two weeks prior to inclusion.
• E2. Patient with lesions of all types on the mucosa of the cheek located on the opposite side of the area affected by an epidermoid carcinoma of the oral cavity which prevents painless removal of the healthy mucosa.
• E3. Patient who had surgery for their epidermoid carcinoma of the oral cavity more than 6 months ago.
• E4. Patient who uses cannabis.
• E5. Patient with another active tumor or HPV-positive tumors.
• E6. Patient under guardianship or curatorship or placed under the protection of justice.
• E7. Pregnant and/or nursing patient.