We have previously reported a proteomics pipeline optimized for identification of exosome proteins purified by the SEC from the cell culture media [30], which allowed to identify above 1200 proteins in EVs released to media by head and neck cancer cell line, including typical exosome markers (CD9, CD63, CD81, ALIX, TSG101, etc.)and excluding co-purified serum proteins from fetal bovine serum complementing culture media [40]. Here, CD81 is linked to head and neck cancer.