Squamous cell cancer of unknown primary (SC-CUP) in the head and neck region is defined as squamous cell lymph node metastases in the neck without an identifiable primary tumour.

The status of “unknown primary” is only manifest after a thorough diagnostic work-up and failure to identify the primary tumour. This is an unfortunate situation, as it often implies extended radiation therapy with significant short and long term morbidity and an increased risk of recurrence of cancer and premature death. The incidence of SC-CUP is approximately 2-10% of all malignant neoplasms in the head and neck region.

However, the number of patients who are suspected of having SC-CUP is significantly higher, probably exceeding 250 patients annually and rising! These high numbers are most likely due to the high rise in incidence of Human Papilloma Virus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) in the western world. The disease often presents with lymph node metastases in the neck and a small or subclinical primary tumour in the lymfoid tissue of the oropharynx. The patients are offered an extended diagnostic work-up based on national guidelines. It includes scans and multiple surgical interventions and is often challenging and time-consuming. In addition to the risk of disease advancement due to delayed treatment initiation, many patients suffer from morbidity, anxiety, and risk of complications caused by the diagnostic procedures. Unfortunately, in a number of patients the primary tumour remains unidentified.