BASIC SCIENCE REVIEW Jeffrey N. Myers, MD, PhD, Section Editor CAN BIOMARKERS PLAY A ROLE IN THE DECISION ABOUT TREATMENT OF THE CLINICALLY NEGATIVE NECK IN PATIENTS WITH HEAD AND NECK CANCER? Robert P. Takes, MD, PhD, 1 Alessandra Rinaldo, MD, 2 Juan Pablo Rodrigo, MD, 3,4 Kenneth O. Devaney, MD, JD, FCAP, 5 Johannes J. Fagan, MBChB, FCS (SA) MMed, 6 Alfio Ferlito, MD, DLO, DPath, FRCS, FRCSEd, FRCSGlasg, FRCSI, FHKCORL, FDSRCS, FRCPath, FASCP, MCAP 2 1 Department of Otolaryngology–Head and Neck Surgery, Radboud University Nijmegen Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: r.takes@kno.umcn.nl 2 Department of Surgical Sciences, ENT Clinic, University of Udine, Udine, Italy 3 Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain 4 Instituto Universitario de Oncologı ´a del Principado de Asturias, Oviedo, Spain 5 Department of Pathology, Foote Hospital, Jackson, Michigan 6 Division of Otolaryngology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Accepted 31 August 2007 Published online 22 January 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20759 Abstract: For most patients with head and neck squamous cell cancer, a treatment decision concerning the neck is required. Since detection of small metastases in lymph nodes is difficult, many of the patients with no detectable metastases receive elective treatment of the neck. Additional information on the met- astatic potential of the primary tumor before treatment may be useful to reduce the number of these elective procedures. Bio- markers may supply such information. Molecules involved in several pathways have been studied, but the complexity of the metastatic process makes it unlikely that a single marker for me- tastasis can de identified. Techniques allowing the study of many factors simultaneously seem to be the most promising ones. In recent years, microarray expression profiling and com- parative genomic hybridization studies have yielded interesting results. If these results can be confirmed in larger studies, they may play a role in future clinical decision making on treatment of the clinically N0 neck. V V C 2008 Wiley Periodicals, Inc. Head Neck 30: 525–538, 2008 Keywords: biomarkers; metastasis; neck dissection; head and neck; cancer One of the basic issues in the treatment of patients with head and neck squamous cell cancer (HNSCC) is the treatment of the clinically N0 neck. If nodal metastases are present, there is gen- eral agreement that the neck should be treated; on the other hand, in the absence of nodal metastasis, the decision to treat the neck is less clear-cut. The problem in clinical practice is that the accuracy of diagnostic (imaging) techniques to assess the neck is still limited. 1,2 Therefore, uncertainty about the true status of the neck remains even after the use of the most advanced imaging techniques. Correspondence to: R. P. Takes V V C 2008 Wiley Periodicals, Inc. Role of Biomarkers in the Decision about Treatment of the Neck HEAD & NECK—DOI 10.1002/hed April 2008 525