Abstract: There are currently no screening tests in routine use for oral and pharyngeal cancer beyond visual inspection and palpation. Described is an improve method of detecting oral and pharyngeal cancer with a saliva sample from a subject. The method includes identifying the presence or absence of a methylation classifier in the saliva the sample. The methylation classifier is determined by the methylation status of a panel of CpG islands in the sample. In an embodiment, the methylation classifier is determined by the methylation status of between 15 and 25 CpG islands, or alternatively, 22 CpG islands. The presence of the methylation classifier indicates a diagnosis of cancer in the subject. In an embodiment, the presence of the methylation classifier is determined with a bisulfite method of determining methylation status of the CpG islands.