9: Head and Neck Carcinoma of Unknown Primary

In some patients, neck nodes may develop but a mucosal or skin primary site may remain elusive. These patients are said to have a head and neck carcinoma of unknown primary. The diagnosis has become less common with improved diagnostic tools. Despite the lack of identification of primary site, long term survival and cure is possible for a number of patients. There is controversy as to the extent of treatment.
Importantly, patients with isolated SCC metastases to supraclavicular nodes rarely have a mucosal primary. These patients typically have either skin or thoracic/abdominal primary tumours.


The workup for a patient with palpable neck nodes includes:

  • History (specifically looking for potential sites such as hoarse voice, previous skin cancers)
  • Examination
    • Oral cavity
    • Nasal vestibule
    • Naso-endoscopy
    • External auditory meatus
    • Skin including scalp
  • Investigations may prove helpful, such as CT of the head and neck, PET scan or MRI.
  • Examination under anaesthesia is indicated for all patients, with biopsy of suspicious lesions and blind biopsies of the tonsils and base of tongue (which harbour > 70% of unknown primary malignancies)
  • Histopathological examination may be helpful; if there is evidence of HPV infection (p16 positivity) a mucosal primary of the oropharynx is extremely likely, whereas oral cavity, nasopharynx or other sites are very unlikely.


Treatment is either surgical or radiotherapy (chemoradiotherapy if N2 disease).

  • Surgical treatment removes the tumour but does not deal with the issue of a mucosal primary or potential spread to the contralateral neck.
  • Chemo/radiotherapy allows treatment of the nodal metastasis as well as any potential primary or microscopic nodal involvement and is usually preferred
    • The ipsilateral neck is always included in the volume
    • Most would recommend treatment to the mucosa. The areas included are controversial. The oropharynx should always be included; the hypopharynx is a likely site in smokers. Nasopharyngeal tumours are rare and often excluded by naso-endoscopy; oral cavity tumours are likewise excluded by thorough oral examination. Inclusion the nasopharynx and oral cavity also significantly increases the toxicity of treatment. Therefore my recommendation would be to include the oropharynx and hypopharynx in smokers; the oropharynx alone in non-smokers with a HPV positive tumour.
    • The contralateral neck adds further toxicity but observational series suggest that including the contralateral neck improves outcomes (progression free and overall survival) by about 10%; this has not been tested in randomised trials. If the contralateral neck is included, I would recommend treatment to the most likely involved nodal sites; that is, levels II, III, IV as well as the level in which the pathological involved node was located.

Chemoradiotherapy requires extensive discussion with the patient to explain the potential benefits and risks of the treatment. This treatment is best delivered with IMRT to improve sparing of the parotid glands.
Dose levels:

  • 66-70 Gy to GTVn
  • 50 Gy to elective sites