Human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, and despite optimal treatment with chemoradiotherapy to the limit of tolerance, many patients will relapse. A number of methods for intensifying treatment of HNSCC have been investigated, leading to the current standards of care. Novel agents targeting tumor cell and stromal signaling, DNA damage response, and immune system are now reaching clinical trials in combination with chemoradiotherapy. In this review, we discuss the evidence for the current treatment of locally advanced human papillomavirus-negative HNSCC, as well as investigational therapies, such as hypoxia modification, molecular targeting of epidermal growth factor receptor family, vascular endothelial growth factor receptor or DNA damage response proteins in combination with radiation therapy.
© 2015 by American Society of Clinical Oncology.