To determine whether ipsilateral radiotherapy affects overall survival, cause-specific survival, or local control in patients with a cancer from an unknown primary of the head and neck compared with comprehensive radiotherapy.

Retrospective medical record review.

Academic tertiary care hospital.

The study population comprised 46 patients with cervical metastases from an unknown primary cancer treated with radiotherapy from 1989 through 2008. Median follow-up was 4.6 years.

All patients were treated with radiation therapy. Radiotherapy target volumes were categorized as either ipsilateral neck only (IPSI) or comprehensive (COMP), including both the potential mucosal surfaces and ipsilateral or bilateral neck. Human papillomavirus (HPV) status, as determined by p16 immunohistochemical analysis, was evaluated for 36 patients (74%).

Overall survival, cause-specific survival, locoregional control, and rate of distant metastases were analyzed.

Overall survival at 2 years and 5 years was 87% and 77%, respectively. Cause-specific survival at 2 years and 5 years was 89% and 81%, respectively. There were no ipsilateral neck failures. There was no difference in overall survival between patients treated with IPSI or COMP radiation therapy. The contralateral neck was controlled in all patients receiving bilateral neck irradiation and in 95% receiving ipsilateral neck irradiation. Of the 34 patients evaluated with p16 immunohistochemical analysis, results for 16 (47%) were positive. There was a nonsignificant trend toward improved overall survival in p16-positive patients (P = .06).

IPSI radiation therapy demonstrated excellent locoregional control with no adverse effect on disease-free survival or overall survival.