Classifying squamous cell carcinoma of the head and neck: prognosis, prediction and implications for therapy.

Traditionally, squamous cell cancers of the head and neck (SCCHN) have been classified by their anatomic location and stage. This system has been unsatisfactory in that it leaves substantial heterogeneity in prognosis and inadequate definition of optimal therapy. The most promising novel marker for superior prognosis in SCCHN is human papillomavirus (HPV). Overexpression of the EGFR bears an adverse prognosis; no marker provides clear predictive power for benefit from EGFR inhibition. Low expression of the DNA repair enzymes and excision repair cross-complementing rodent repair deficiency (ERCC1) and x-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) may predict chemotherapy and chemoradiotherapy sensitivity. Tumors expressing cyclin D1 have a poor prognosis. Genomic characterization has subdivided SCCHN into four categories with clear biologic themes. Basal cancers express high levels of TGF-α and have other perturbations of the EGFR axis. Mesenchymal cancers show evidence for epithelial to mesenchymal transition. Atypical cancers lack both EGFR amplification and deletion of 9p; they also have a higher rate of HPV positivity than the other groups. Classical tumors demonstrate gene signatures similar to those previously associated with exposure to cigarette smoke; patients with this signature had a greater smoking history than patients in the other groups.