Molecular profiling of head and neck squamous cell carcinomas in North-eastern Italy identifies possible tumour cell...

Head and Neck Squamous Cell Cancer (HNSCC) originates from the oral cavity, oropharynx, hypopharynx and larynx, and it ranks sixth among global cancers. Despite modest 5-year survival gains, the integration of molecular personalization lags behind and there is an urgent need to develop novel therapies and biomarkers.

This study outlined the somatic mutational profile of 15 HNSCC-enriched genes in a case series from North-eastern Italy, the region with the highest national HNSCC incidence. We conducted a comparative analysis with prior case studies and assessed the prognostic implications of the mutations that we found in these genes.

Consistent with previous studies, oral cavity tumours showed a lower gene mutation frequency. We highlighted a significant enrichment of somatic AJUBA mutations in the hypopharyngeal region, linked to a poorer prognosis. Moreover, KMT2C mutations co-occurring with CDKN2A or NOTCH1 mutations were associated with a worse prognosis. At the same time, only 7 % of the cases exhibited mutations that are predictive biomarker in HNSCC according to compelling clinical evidence but that need further investigation in a clinical trial setting.

Our findings underlined novel differences in somatic gene mutations among the four anatomic sites. However, at present, the identified mutations cannot yet be considered predictive biomarkers either for the lack of supporting clinical findings or for the lack of approved targeted therapies in HNSCC. This underscores the imperative for continued investigation into the biology of HNSCC to unveil novel vulnerabilities that can be leveraged to enhance patient treatment strategies.