Head and Neck Cancer

Clinical Background

Squamous cell carcinoma (SCC) of the head and neck is the most common malignancy of the upper aerodigestive tract.

Epidemiology

Prevalence - 34,000 new cases per year in the U.S.
Age - 50-60 years
Sex - males: females; 3:1
Ethnicity - African Americans more at risk than Caucasians

Risk Factors

Tobacco use - 5-25 fold higher risk
Alcohol use - if combined with smoking, geometrically increases risk
Occupational exposures
- Exposure to nickel refining, chromium, mustard gas, radium
- Woodworking and tanning byproducts
Viral infection
- Epstein-Barr - associated with nasopharyngeal carcinoma
- HPV 16/18/31 - most highly associated with carcinoma of lingual and palatine tonsils
Betel nut chewing

Pathology

The aerodigestive tract is lined with squamous cells
The majority of cancers arising in the aerodigestive tract are of squamous cell origin (90%)
Increased incidence over the past 10 years of the disease due to increased cancer of the base of the tongue and tonsils
Premalignant diseases (leukoplakia, erythroplakia, and dysplasia) can precede frank malignancy
SCC antigen
- SCC antigen is expressed in normal epithelium and epithelial tissues
- Neutral forms of SCC antigen normally remain inside the cell
- Acidic SCC antigen is released and is often elevated in patients having SCC or other nonmalignant squamous cell lesions
Lipid associated sialic acid
- Elevated concentrations of sialic acid are noted in inflammatory disorders and significant tissue necrosis
- In cancer patients, elevated concentrations of sialic acid can be from the tumor cell surfaces as well as the nonspecific inflammatory responses associated with the malignancy
- Malignant cells often exhibit aberrant sialylation, which has been implicated in the loss of contact inhibition and the metastatic potential of these cells

Clinical Presentation

Oral cavity - nonhealing ulcers of the floor of the mouth, tongue, buccal mucosa, hard palate; pain
Hypopharynx - hoarseness, dysphagia, otalgia, enlarged cervical nodes
Pharynx - tonsils, sore throat, otalgia, odynophagia
Nasopharyngeal - usually late symptoms of bleeding, obstruction, cranial nerve palsy; otitis media unresponsive to antibiotics
Salivary glands - swelling, adenopathy

See Also

Lung Cancer

Nicotine & Metabolites

Tests

Tests generally appear in the order most useful for common clinical situations

Test name: Squamous Cell Carcinoma Antigen, Serum

ARUP #: 0081054

Methodology: Enzyme-Linked Immunosorbent Assay

Use:

Monitor patients with squamous cell carcinoma with serial determinations

Most useful for monitoring cancer recurrence following head and neck surgery for the removal of squamous cell carcinoma (recommend testing 4 weeks prior to surgery)

Limitations:

Elevated in patients with a variety of cancers

This test is not intended for use in diagnosing cancer

Results obtained with different assay methods or kits cannot be used interchangeably

Normally present in saliva, sweat, and respiratory secretions, so precautions must be taken to prevent sample contamination with these fluids

Follow-up:

May be used as a sequential test for following tumor progression (Increasing SCC antigen concentrations are associated with tumor stage progression)

In cases where elevated or increased SCC antigen concentrations are observed, retesting of a new sample is indicated to exclude contamination

Test name: Lipid Associated Sialic Acid

ARUP #: 0080467

Methodology: Spectrophotometry

Use:

Use in conjunction with other tumor marker tests in managing select cancer patients (head and neck cancer, gynecological cancer, brain cancer, colorectal cancer and melanoma)

Limitations:

Use this test only in conjunction with other tumor marker tests

Lipid-associated sialic acid (LASA) has lower specificity and sensitivity than most tumor markers

May be modestly elevated in diabetes mellitus type 2

Test name: EGFR by FISH

ARUP #: 0049234

Methodology: Fluorescence in situ Hybridization

Use:

May be a prognostic or predictive marker

Limitations:

Role in management of head and neck squamous cell carcinomas has not yet been well established

Follow-up:

Test name: Immunohistochemistry Stain Offering

ARUP #: arup005

Methodology: Immunohistochemistry

Use:

For fixed tissue samples, consultative services as well as immunohistochemical staining for EGFR, EGFR (H-11), EBV LMP, p53, NSE and ERA (moc-31) are available

References

General References

Agarwal V, Branstetter BF, Johnson JT. Indications for PET/CT in the Head and Neck. Otolaryngol Clin North Am. 2008;41(1):23-49.

Browman GP, Hodson DI, Mackenzie RJ, Bestic N, Zuraw L. Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis. Head Neck. 2001;23(7):579-589.

Ernster JA, Sciotto CG, O'brien MM, Finch JL, Robinson LJ, Willson T, Mathews M. Rising Incidence of Oropharyngeal Cancer and the Role of Oncogenic Human PapillomaVirus. Laryngoscope. 2007;:-.

Gillison ML. Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck. 2007;29(8):779-792.

Kirsch C. Oral cavity cancer. Top Magn Reson Imaging. 2007;18(4):269-280.

Konkimalla VB, Suhas VL, Chandra NR, Gebhart E, Efferth T. Diagnosis and therapy of oral squamous cell carcinoma. Expert Rev Anticancer Ther. 2007;7(3):317-329.

Lothaire P, de Azambuja E, Dequanter D, Lalami Y, Sotiriou C, Andry G, Castro G Jr, Awada A. Molecular markers of head and neck squamous cell carcinoma: promising signs in need of prospective evaluation. Head Neck. 2006;28(3):256-269.

Micke O, Bruns F, Schafer U, Horst E, Buntzel J, Willich N. The clinical value of squamous cell carcinoma antigen in patients irradiated for locally advanced cancer of the head and neck. Anticancer Res. 2003;23(2A):907-911.

Molina R, Filella X, Auge JM, Fuentes R, Bover I, Rifa J, Moreno V, Canals E, Vinolas N, Marquez A, Barreiro E, Borras J, Viladiu P. Tumor markers (CEA, CA 125, CYFRA 21-1, SCC and NSE) in patients with non-small cell lung cancer as an aid in histological diagnosis and prognosis. Comparison with the main clinical and pathological prognostic factors. Tumour Biol. 2003;24(4):209-218.

Ohno T, Nakayama Y, Nakamoto S, Kato S, Imai R, Nonaka T, Ishikawa H, Harashima K, Suzuki Y. Measurement of serum squamous cell carcinoma antigen levels as a predictor of radiation response in patients with carcinoma of the uterine cervix. Cancer. 2003;97(12):3114-3120.

Quon H, Liu FF, Cummings BJ. Potential molecular prognostic markers in head and neck squamous cell carcinomas. Head Neck. 2001;23(2):147-159.

van der Waal R, van der Waal I. Oral non-squamous malignant tumors; diagnosis and treatment. Med Oral Patol Oral Cir Bucal. 2007;12(7):E486-E491.

Wycliffe ND, Grover RS, Kim PD, Simental A Jr. Hypopharyngeal cancer. Top Magn Reson Imaging. 2007;18(4):243-258.

References from the ARUP Institute for Clinical and Experimental Pathology Research®

Layfield LJ. Fine-needle aspiration in the diagnosis of head and neck lesions: a review and discussion of problems in differential diagnosis. Diagn Cytopathol. 2007;35(12):798-805.

Willmore-Payne C, Holden JA, Layfield LJ. Detection of. Mod Pathol. 2006;19(5):634-640.

Medical Reviewers

Grenache, David G., Ph.D. Medical Director, Special Chemistry at ARUP Laboratories; Assistant Professor, Clinical Pathology, University of Utah

Layfield, Lester , M.D. Fine-Needle Aspiration Services and Molecular Diagnostics at ARUP Laboratories; Professor and Division Head, Anatomic Pathology, University of Utah

Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah

Comprehensive Review: May 2008
Last Update: May 2008