J-P Machiels underlines the importance of the EGFR target in head & neck cancer, as monoclonal antibodies against the EGFR target improve outcome. However, a limitation with anti-EGFR therapy exists, as a minority of patients will have objective response and the issue in head & neck cancer, compared to other cancers, is that there are no predictive biomarkers. He goes on to discuss the differences, at the molecular level, between HPV-positive and negative disease.