Discovery of the Unknown Primary Tumor Is Associated with Improved Disease-Specific Survival

Clinical Question

Does detection of the occult primary tumor result in improved survival in head and neck squamous cell carcinoma?

Background: The management of patients with unknown primary squamous cell carcinoma presenting with cervical metastases is evolving, with the recognition that human papilloma virus (HPV) disease often arises from the oropharynx and the advent of new transoral techniques such as transoral robotic surgery (TORS) that allow removal of lingual tonsillar tissue to improve the yield of unknown primary detection.

Study design: Retrospective chart review of adult patients diagnosed with unknown primary squamous cell carcinoma presenting with cervical metastases between 1980 and 2010. Patients without an obvious primary after complete head and neck exam including flexible laryngoscopy, operative laryngoscopy, and imaging by CT, MRI, or PET comprised the study population. A subset of patients in whom the primary was subsequently found was matched to patients without a known primary by nodal stage and age and comprised the study population.

Setting: University of Pittsburgh.

Synopsis: Of 136 patients meeting study criteria, the primary site was found in 22 patients, who were matched to 22 patients in whom the primary was not found. TORS was used in five patients in whom the primary was found and two patients in whom the primary was not found. There was no difference between matched groups in the use of ipsilateral neck dissection (45%), radiation (100%), chemoradiation (91%), or extracapsular extension in nodes when neck dissection was performed (73%). Patients in whom the primary site was found were more likely to have HPV-positive tumors (96%) compared with patients in whom the primary was not found (36%). Identification of the primary site was associated with significantly improved disease-specific survival (HR=0.1[0-0.9]) and disease-free survival (HR=0.3[0.1-0.9]), with improved survival for HPV disease.

Bottom line: Discovery of the unknown primary is associated with improved disease-specific survival, which is likely due to HPV-positive status. Discovery of the unknown primary is more likely for patients with HPV-positive tumors in whom pharyngeal and lingual tonsillectomy are more likely to yield an occult primary.

Citation: Davis KS, Byrd JK, Mehta V, et al. Occult primary head and neck squamous cell carcinoma: utility of discovering primary lesions. Otolaryngol Head Neck Surg. 2014;151:272-278

—Reviewed by Christine Gourin, MD