Heterogeneity of Oral Carcinogenesis: From PrEneoplasia to Invasive Squamous Cell Carcinoma

Heterogeneity of Oral Carcinogenesis: From PrEneoplasia to Invasive Squamous Cell Carcinoma

The goal of this project is to characterise the heterogeneity of all cell populations (tumour cells, stromal and immune microenvironment) present in the tumor and their normal (and OPMD) counterparts by scRNAseq in OSCC patients. Additionally, the study will evaluate the effectiveness of non-invasive cytobrushes as a diagnostic tool compared to traditional biopsies.

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.

OSCC treatment is based on surgery and/or radiotherapy and/or chemotherapy. Immune Check point Inhibitors (ICIs) targeting PD-1 have been approved for recurrent and metastasic OSCC. However, only 15-20% of these patients are treated thanks to this anti-PD-1. Thus, there is a real need to improve the efficacy of ICIs in the treatment of HNSCC. The scRNAseq is a method which allows to study the tumoral heterogeneity, the microenvironment and the dynamic and regulation mecanisms in cells cancer. This technology could improve patient stratification, identify pronostic biomarkers, constitute an important tool in the therapeutical take care and lead to understand tumoral evolution and develop new prevention strategies.

The project is organized into three cohorts:

• Cohort A (OSCC): Designed to compare malignant cells directly with their healthy and pre-malignant counterparts within the same patient.
• Cohort B (OPMD): Focused on patients with potentially malignant lesions but no active cancer.
• Cohort C (Cyto-OPMD): Validating a non-invasive sampling method. The goal is to determine if a cytobrush can provide the same high-quality genomic data as a biopsy.

By combining these approaches, the project aims to characterize the heterogeneity of all cell populations (tumour cells, stromal and immune microenvironment) to improve the global management of patients.

Inclusion Criteria:

• I1: Male or female at least 18 years old.
• I2: For Cohort A: patients with OSCC who undergo surgery. For cohorts B and C: patients with OPMD.
• I3: Patient who has agreed to participate in this research and sign consent.
• I4: Patient affiliated to a medical insurance.
• I5: Patient who have not previously received any anticancer treatment (radiotherapy, chemotherapy, or immunotherapy)

Exclusion Criteria:

• NI1: For cohorts B and C: Patient at high risk of bleeding, such as those receiving anticoagulant or antiplatelet therapy, those with coagulation disorders, or those with a history of severe bleeding within the two weeks prior to enrollment.
• NI2: Pregnant or nursing woman.
• NI3: Contraindication to general anesthesia.
• NI4: Suspicion of rare tumor of particular histology other than squamous cell carcinoma (Sarcoma...).
• NI5: Patient under curatorial or guardianship or placed under the protection of justice.