• Head and neck cancer;
  • unknown primary;
  • survival outcomes;
  • radiation;
  • chemoradiation;
  • surgery;
  • Level of Evidence: 2a



We systematically reviewed the published experience on the treatment outcomes of patients with head and neck cancer of unknown primary (CUP) to determine if treatment modality affects survival outcomes.

Study Design:



A comprehensive literature search was performed for articles reporting survival outcomes for CUP in the head and neck published within the last 12 years.


Eighteen studies with 1,726 patients met the inclusion criteria. All studies reported at least 5-year survival outcomes. Thirteen of the 18 studies also reported 5-year survival based on N stage, and six reported 5-year survival based on presence of extracapsular extension (EC). Overall 5-year survival in the entire group was 48.6%. Five-year survival based on N stage was as follows: N1 = 60.8%, all N2 = 51.1%, N2a = 63.6%, N2b = 42.5%, N2c = 37.5%, and N3 = 26.3%, with P < .001 on multivariate analysis. Patients who underwent surgical treatment with either postoperative radiation or chemoradiation had a 5-year survival of 52.4% compared to 46.6% for those treated with chemoradiation alone; however, this difference was not statistically significant. Patients with EC had a 5-year disease-specific survival of 56.9% compared to 81.5% for those without EC (P = .01).


In patients with CUP, survival outcomes are most significantly influenced by clinical stage at time of diagnosis. No significant 5-year survival difference was seen between patients treated with radiation or chemoradiation alone when compared to patients who also received surgical treatment.