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

Abstract

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.

Keywords::

• gene signatures
• head and neck
• human papillomavirus
• marker
• squamous cell carcinoma

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• In the current standard of care, squamous cell carcinoma of the head and neck is classified by site of origin and stage.

• Human papillomavirus (HPV) is a virus that can drive carcinogenesis. Cancers driven by HPV bear a superior prognosis to those driven by tobacco use, but it is not yet clear if or how optimal treatment is different for the HPV+ patient.

• High expression of EGFR bears an adverse prognosis. The EGFR inhibitor cetuximab is active against head and neck cancer. It is not clear whether EGFR expression or HPV can predict which patients derive benefit from cetuximab.

• Expression of the DNA repair enzymes excision repair cross-complementing rodent repair deficiency and x-ray repair complementing defective repair in Chinese hamster cells 1 predict sensitivity to chemotherapy and to chemoradiotherapy. No prospective data define optimal use of this information in clinical practice.

• Overexpression of CCND1 bears an adverse prognosis.

• Genomic characterization classifies squamous cell carcinoma of the head and neck into four groups with distinct biologic themes: basal, mesenchymal, atypical and classical.

Notes