The Use of Ultrasound in the Search for the Primary Site of Unknown Primary Head and Neck Squamous Cell Cancers

Background: Although human papillomavirus detection in cervical lymph nodes of head and neck squamous cell cancers (HNSCC) of unknown primary site (UP) is indicative of a primary tumor of the oropharynx (OP), localization can remain elusive. Therefore, we investigated ultrasonography (US) for the identification of the primary tumor.

Methods: Eligible cases had HNSCC of UP after evaluation by a head and neck surgical oncologist. Controls were healthy volunteers. Transcervical and intraoral ultrasonography was performed by a standard protocol using convex (3.75-6.0 MHz and 5-7.5 MHz) transducers. US findings were compared with operative examination (exam under anesthesia, direct laryngoscopy) and biopsies. The primary outcome of interest was the presence or absence of a lesion on US.

Results: 10 cases and 20 controls were enrolled. PET/CT scans were negative/nonspecific (9), or suspicious (1) for a primary lesion. On US, predominantly hypoechoic (9 of 10) lesions were visualized consistent with base of tongue (n=7) or tonsil (n=3) primary tumors. On operative examination, 5 of 10 were appreciated. Two additional primaries were confirmed with biopsies "directed" by preoperative US. This represents an overall diagnostic rate of 70%, which is 20% higher than our detection rate for 2008-2010. The three cases in which a suspicious lesion was visualized on US, yet remained UP despite further interventions, could represent false positives, misclassification or operator variability. No lesions were suspected among the controls.

Conclusion: Ultrasound has promise for detection of UPs of the OP and therefore warrants further investigation.