The aim of the present study was to compare the three different algorithms in order to improve the clinical performance of methylated ccfDNA as a biomarker with the example of SEPT9 and SHOX2. This study was carried out based on a reevaluation of recently published data [3] from a prospective cohort study including HNSCC patients. This evidence concerns the gene SHOX2 and head and neck squamous cell carcinoma.