Abstract
BACKGROUND: Despite the vivid progress in molecular and genetic profiling, extensive diagnosis and multiple therapeutic modalities, cancers of unknown primary in the head and neck region continue to be a formidable challenge. AIM: The purpose of the review is to present the most recent and well-established findings concerning cancers of unknown primary (CUPs) in the head and neck patients and consequently to provide medical specialists with essential information regarding the biology, pathology, histology, diagnosis and treatment of CUP in the head and neck region. MATERIAL AND METHODS: The Medline/PubMed database was searched by using the following keywords "CUP", "cancer of unknown primary", "CUP biology", "head and neck". The references of the publications of interest were also screened for relevant papers. There were no limitations in regard to the publication date. CONCLUSION: Unique biology and pathophysiology prompt the management of CUP to be demanding. The vivid rise in HPV-related CUPs during the last 20 years has put more focus on this phenomenon. New findings concerning the enigmatic biology of CUP provide fundaments for targeted therapy. Despite the availability of various diagnostic methods, the diagnosis of CUP continues to be a time-consuming, strenuous process that eventually provides answers. It remains controversial as to what combination of treatment methods is the most effective. There is no consensus on the value of combining chemotherapy with radiotherapy. Highly specific surgical treatments for particular histological types of CUP produce more satisfactory results. It is paramount to establish reliable guidelines concerning the diagnosis and treatment of CUP patients.