The use of non-invasive biomarkers such as circulating tumor DNA (ctDNA) in head and neck tumors may be of relevance in early diagnosis and eventually improved outcome. We evaluated two different approaches from two case series in Europe and South America including (i) targeted screening of ctDNA mutations, and (ii) detection of TP53 mutations in plasma and oral rinses without previous knowledge of mutational status in tumor samples. Targeted sequencing in 5 genes identified ctDNA mutations in plasma among 42% of HNSCC cases, 67% of who were early stage cases. No association was found between ctDNA mutation detection and overall survival. Sequencing of the entire coding region of the TP53 gene resulted in identification of TP53 mutations in 76% of tumor cases. However, concordance of mutation detection was low between tumor, oral rinses (11%) and plasma (2,7%) samples. Identification of 5 pathogenic TP53 mutations in oral rinses from 3 non-cancer controls gives additional evidence of mutation occurrence in individuals without a diagnosed cancer and presents an additional challenge for the development of ctDNA diagnostic assays.

Charles University 1st Faculty of Medicine Prague 116 36 Czech Republic

CRO Aviano National Cancer Institute Aviano 33081 Italy

Current present address Rajiv Gandhi Centre for Biotechnology Trivandrum 695010 India

Departamento de Saúde Coletiva Faculdade de Ciências Médicas da Santa Casa de São Paulo São Paulo CEP01221 020 Brazil

Department of Hygiene Epidemiology and Medical Statistics School of Medicine National and Kapodistrian University of Athens Athens 11527 Greece

Institute of Nutrition Genetics and Metabolism Research Faculty of Medicine Universidad El Bosque Bogotá 110121 Colombia

Instituto Angel Roffo Buenos Aires C1417DTB Argentina

International Agency for Research on Cancer Lyon 69372 France

Laboratory of Public Health and Population Studies University of Padova Padova 35122 Italy

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Gene Mutations in Circulating Tumour DNA as a Diagnostic and Prognostic Marker in Head and Neck Cancer-A Systematic Review