Current issues in combined modality therapy in locally advanced head and neck cancer

Curative treatment for patients with locally advanced squamous cell carcinomas of the head and neck (SCCHN) is complex and multidisciplinary. Our understanding of the optimal management of this disease has improved over the years, incorporating refined surgical approaches, better radiotherapy delivery methods, and greater use of systemic therapies. Investigation into shifting epidemiology patterns has uncovered two biologically and clinically distinct diseases: the smoking-related entity and the increasingly common malignancy associated with human papilloma virus (HPV). Prognosis favors the latter, driving newer investigations into dose de-intensification to limit toxicities in patients with HPV-driven disease, and alternatively intensifying treatment to improve tumor control in those with a significant smoking history. In this review, I describe the most recent progress in the multi-modal integration of radiotherapy and chemoradiotherapy, and the role of targeted agents and personalized therapy, and conclude with a discussion of the relevance of these innovations with respect to HPV tumor status.