Head and neck cancer of unknown primary (HNCUP) is increasingly encountered in both community otolaryngology practice and the academic head and neck cancer program. A stepwise diagnostic evaluation will identify many primary sites. However, true HNCUP remains common in high-volume practices after appropriate examination, imaging, and biopsies. The prognosis for the majority of the patients is good, owing to the common association with high-risk HPV, and putative oropharyngeal primary origin. With high oncologic control rates, judicious treatment selection is essential to optimize functional outcomes.
Keywords: HPV; Head and neck cancer; Oropharyngeal cancer; Unknown primary.