INTRODUCTION Head and neck squamous cell carcinoma (HNSCC) that presents as carcinoma of unknown primary (CUP) represents a difcult challenge for the practising clinician. With improvements in diagnostic techniques such as cross-sectional imaging, molecular diagnostics, robotics and positron emission tomography (PET) scanning, clinicians are now able to identify a higher proportion of primary sites in patients presenting with CUP than before. The most common presentation of CUP in the head and neck is in the context of human papillomavirus (HPV)-associated oropharynx (HPV+OPSCC) carcinoma. As the year-onyear numbers of HPV+OPSCC are increasing in the developed world, it is likely therefore that the incidence of CUP is also increasing.1-3
DEFINITION AND HISTORICAL BACKGROUND The term carcinoma of unknown primary (CUP) represents a heterogeneous disease entity characterized by the presence of clinically overt metastatic disease in the absence of a clinically or radiologically obvious primary tumour.