Fol. Biol. 2023, 69, 107-115

Germline Pathogenic Variants in Squamous Cell Carcinoma of the Head and Neck

Tereza Drbohlavová1, Soňa Argalácsová2, Jana Soukupová3, Michal Vočka2

1Institute of Radiation Oncology, First Faculty of Medicine, Charles University and Bulovka University Hospital, Prague, Czech Republic
2Department of Oncology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
3Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic

Received November 2023
Accepted December 2023

Head and neck squamous cell carcinoma (HNSCC) presents a significant global health problem with variable geographic distribution and risk factors, including tobacco and alcohol abuse, human papillomavirus infections, and genetic predisposition. While the majority of cases are sporadic, several well-defined hereditary syndromes have been associated with a higher risk of developing HNSCC including Li-Fraumeni syndrome, Fanconi anaemia, Bloom syndrome, familial atypical multiple mole melanoma, and dyskeratosis congenita. There is also evidence of familial clusters of HNSCC, suggesting a genetic component in the development of the disease. Germ­line genetic testing in HNSCC using next-generation sequencing has revealed a wide range of germline variants, some of which were not anticipated based on standard guidelines. These variants may influence treatment decisions and have the potential to be targeted with precision medicine in the future. Despite these advances, routine germline genetic testing for HNSCC is not currently recommended and remains reserved for HNSCC cases with early onset or strong family cancer history. However, the increasing availability of germline genetic testing warrants development of more comprehensive and standardized testing protocols. Germline genetic testing also has the potential to influence precision-guided treatment in HNSCC patients carrying germline pathogenic variants.


This study was supported by the institutional support of the Ministry of Health of the Czech Republic (grants Nos. NU20-03-00283, DRO VFN 64165, and DRO MMCI 00209805) and Charles University institutional programmes (COOPERATIO, Oncology and Haematology).


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