Approach to the Patient with Unknown Primary Squamous Cell Carcinoma of the Head and Neck

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.