Head and neck cancer

Abstract

Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Moreover, systemic therapy including chemotherapy and molecularly targeted agents--namely, the epidermal growth factor receptor inhibitors--has been successfully integrated into potentially curative treatment of locally advanced squamous-cell carcinoma of the head and neck. In deciding which treatment strategy would be suitable for an individual patient, important considerations include expected functional outcomes, ability to tolerate treatment, and comorbid illnesses. The collaboration of many specialties is the key for optimum assessment and decision making. We review the epidemiology, molecular pathogenesis, diagnosis and staging, and the latest multimodal management of squamous cell carcinoma of the head and neck.

Conflict of interest statement

Conflict of interest statement

AA has been a consultant to Amgen and Imclone. He has received research support from the National Cancer Institute, Genentech, Lilly Oncology, Bristol-Myers Squibb, Pfizer, Novartis, Millenium Pharmaceuticals, M’s Science Corporation, and AstraZeneca. He also received honoraria from Genentech and AstraZeneca. MVK has no conflict of insterest to declare. DR has been a consultant to BMS, Amgen, Imclone, Lilly Oncology, Sanofi-Aventis, Array Biopharm, and GenMab. He is on the speaker’s bureau for BMS, Imclone, and Medimmune, and has received grants from AstraZeneca and Millennium Pharmaceuticals. RLF has received research support from the National Cancer Institute, the National Institute of Dental and Craniofacial Disorders, Amgen, and Altor Biosciences. He has been a consultant to Bristol-Myers Squibb, Imclone, and Altor Biosciences.

Figures

Figure 1:. Presentation of phenotypical progression and accumulated molecular alterations in head and neck carcinogenesis

Histological evolution shown in haematoxylin and eosin specimens (×200) parallels genetic and epigenetic events. Modified from references and . EGFR=epidermal growth factor receptor. PTEN=phosphatase and tensin homologue.

Figure 2:. Molecular signalling pathways and novel targeted agents for the treatment of SCCHN

There is considerable cross-talk between various signalling pathways. Various strategies have been developed to inhibit these pathways, such as mAbs; single-selective, dual-selective, or multi-selective tyrosine kinase inhibitors; and nucleic acid-directed gene silencing molecules (eg, AS ODN and RNA interference—siRNA and ribozymes). Representative agents that are used in human beings are listed in the figure. AS ODN=antisense oligodeoxynucleotide. EGFR=epidermal growth factor receptor. GPCR=G-protein-coupled receptor. HER2= human epidermal receptor 2. IKK=inhibitor κB. JAK=Janus kinase. mAb=monoclonal antbodies. MAPK=mitogen-activated protein kinase. mTOR=mammalian target of rapamycin. NF=nuclear factor. PDKI=pyruvate dehydrogenase kinase, isozyme 1. PI3K=phosphatidylinositol-3-kinase. PLCγ=phospholipase-Cγ. PKC=protein kinase. SCCHN=squamous cell carcinoma of the head and neck. STAT=signal transducers and activators of transcription. TKI=tyrosine kinase inhibitor. VEGFR=vascular endothelial growth factor receptor.

Figure 3:. Various stages of squamous cell carcinoma of the head and neck

(A) Premalignancy evidenced by leukoplakia on the right true vocal fold; (B) early oral tongue cancer in a young, non-smoking woman; (C) stage T2 laryngeal carcinoma, potentially treatable with radiation or surgery; and (D) pathology specimen post-total laryngectomy, which is a standard procedure for large volume, destructive laryngeal cancers.

Figure 4:. Combined PET-CT scan used for staging and response assessment in locally advanced squamous cell carcinoma of the head and neck

Axial fused images showing (A) locally advanced oropharyngeal squamous cell carcinoma with massive lymphadenopathy, staged as T4N3; (B) induction treatment with cisplatin, docetaxel, and cetuximab (on a research protocol) resulted in complete response in the primary and partial response in regional lymph nodes; and (C) further improvement after completion of radiotherapy with concurrent cisplatin and cetuximab. Physiological uptake is seen in the floor of the mouth. Subsequent neck dissection and biopsy of primary tumour showed a complete pathological response.

Figure 5:. Late effects of radiation might result in poor organ function and quality of life

Laryngoscopic view of (A) normal pharynx; and (B) pharynx with severe fibrosis several years after curative chemoradiotherapy.