Head and neck squamous cell carcinoma (HNSCC), France's 5th most common cancer (15,000 annual cases), presents significant public health challenges due to high morbidity and functional/aesthetic sequelae from treatments (mutilating surgery, radiotherapy, chemotherapy). Major risk factors, tobacco and alcohol, create a chronic inflammatory environment promoting tumor development. The upper aerodigestive tract microbiome, influenced by these exposures and local alterations (necrosis, bleeding, ulcerations), is emerging as a potential factor in tumor progression, severity biomarker, or therapeutic target, though its exact role (cause or consequence) remains to be elucidated
Objectives:
* Primary: Compare bacterial microbiome composition between tumor tissue, adjacent healthy mucosa, and pharyngeal secretions
* Secondary:
* Correlate microbiome diversity/composition with clinical and epidemiological characteristics
* Identify microbiome variations by tumor stage, histology, and infiltration
* Discover diagnostic/prognostic microbial markers
* Analyze somatic variants (SNP/CNV) via whole-genome sequencing (WGS) and their association with microbiome profiles and clinical parameters
Study Design: Prospective, cross-sectional study with paired design (each patient serves as their own control to minimize genetic variation biases)
Methods:
* Samples: Tumor, adjacent healthy tissue, and pharyngeal secretions (3 samples/patient)
* Sequencing: Metagenomic sequencing (complete bacterial genomes) when biomass permits, or targeted 16S rRNA sequencing to identify dominant genera.
* Pilot study: 20 patients to select the optimal technique and validate feasibility, particularly assessing DNA quantity in these low-biomass environments
Population: Adults with suspected HNSCC scheduled for panendoscopy
Exclusion criteria: Recent antibiotics/corticosteroids (12 weeks), immunosuppression (uncontrolled HIV, active hematologic malignancies, autoimmune diseases on immunosuppressants, organ/stem cell transplants, uncontrolled diabetes), immunomodulatory treatments (3 months), recurrence, pregnancy, non-French speakers, legal guardianship, or lack of social security.
Safety: No additional risks beyond standard panendoscopy.
Expected impact: This approach may pave the way for innovative diagnostic or therapeutic strategies based on microbiome modulation in HNSCC.