Head and Neck Cancer

Indications for Testing

Persistence of symptoms listed in clinical presentation (see Clinical Background tab), particularly hoarseness, sore throat or dysphagia

Laboratory Testing

HPV testing may help identify likely location of tumor if cervical nodes are sole presentation
- Usually oropharyngeal tumor (tonsillar in particular)
- Usually identified in younger nonsmokers
- Better prognosis

Histology

Gold standard for diagnosis – usually obtained via endoscopy, biopsy; fine needle aspiration of mass
Immunohistochemistry
- p16 for oropharyngeal carcinomas; indicative of better prognosis
In situ hybridization
- HPV for oropharyngeal carcinomas; indicative of better prognosis
- EBV for nasopharyngeal carcinoma

Imaging Studies

CT/MRI/PET – establish local and regional extent of disease
- PET – 90% sensitivity and 94% specificity in detecting nodal metastases
  - CT – 82% sensitivity and 85% specificity
- PET – also useful in treatment planning and monitoring

Prognosis

Markers
- HPV – HPV-positive tumors have improved prognosis
- EGFR – high levels indicate poor prognosis
  - May be useful in establishing treatment regimens
- p53 – may predict poor prognosis
- HER2 – variably expressed but may be associated with improved prognosis
Stage at diagnosis helps predict survival
Presence of comorbidity – strong predictor of mortality in head and neck cancers
Nature and location of tumors have great impact on patient perceptions for future quality of life and may determine treatment options that ultimately affect patient mortality

Differential Diagnosis

Non-neoplastic
- Congenital
  - Thyroglossal duct cyst
  - Branchial cleft cyst
  - Hemangioma
  - Lymphangioma
  - Dermoid
- Infectious
  - Acute lymphadenitis
  - Abscess/deep-space neck infection
  - Sialadenitis
  - Viral
    - EBV
    - Cytomegalovirus
    - HIV
  - Bacterial
    - M. tuberculosis
    - Bartonella spp
  - Parasitic
    - Toxoplasma gondii
- Systemic disease
  - Sjögren syndrome
  - Kimura disease
  - Castleman disease
Neoplastic
- Benign
  - Lipoma
  - Salivary tumor
  - Thyroid goiter
  - Paragangliomas
- Malignant
  - Salivary
  - Thyroid
  - Metastatic carcinoma
  - Sarcoma
  - Lymphoma
    - B-cell
    - T/NK-cell
  - Melanoma

SCC antigen
- Monitoring test only (not intended for use in diagnosis)
- Serial determinations (pre- and post-surgery) – most useful in following cancer recurrence
- Antigen levels decrease to normal levels approximately 96 hours after removal of lesion
LASA – limited use as a marker in SCC
EBV DNA quantitative PCR – useful for monitoring disease progression

Squamous cell carcinoma (SCC) of the head and neck is the most common malignancy (90%) of the upper aerodigestive tract. Less common malignancies include melanoma, sarcoma, lymphoma and oral metastases.

Epidemiology

Incidence
- >49,000 new U.S. cases during 2010 (represents 3% of new cancers)
- >600,000 new cases worldwide
- Increased incidence over the past 10 years
  - Attributed to increasing prevalence of human papillomavirus (HPV); linked to practice of oral sex with multiple sex partners
  - Cancer of the base of the tongue and tonsils (especially in <45 age group)
Age – peaks in 50s
- Tumors associated with HPV peak in mid 40s
Sex – M>F, 3:1
Ethnicity – occurs more often in African Americans than Caucasians

Risk Factors

Tobacco use – increases risk five- to 25-fold
Alcohol use – when combined with smoking, risk increases geometrically
Occupational exposures
- Nickel refining, chromium, mustard gas, radium
- Woodworking and tanning byproducts
Viral infection
- Epstein-Barr virus (EBV) – associated with nasopharyngeal carcinoma
- HPV types 16, 18, 31 – highly associated with carcinoma of lingual and palatine tonsils
  - Tend not to be associated with smoking or alcohol consumption
Betel nut chewing
Family history – 1.2- to 2.3-fold higher risk
Primary head and neck tumor increases risk for secondary tumors in other head and neck sites and for tumors of lung, esophagus and other sites sharing similar risk factors

Pathophysiology

Aerodigestive tract is lined with squamous and respiratory epithelium
Premalignant disease (epithelial dysplasia) may precede frank malignancy
SCC antigen
- SCC antigen expressed in normal epithelium and epithelial tissues
- Neutral SCC antigens normally remain inside the cell
- Acidic SCC antigens are released and often elevated in patients with SCC or nonmalignant squamous cell lesions
Lipid-associated sialic acid (LASA)
- Elevated LASA concentrations are noted in inflammatory disorders with significant tissue necrosis
- Cancer patients – elevated LASA concentrations can result from tumor cell surfaces and from nonspecific inflammatory responses associated with the malignancy
- Malignant cells often exhibit aberrant high sialylation
  - Implicated in contact inhibition loss and increased metastatic potential

Clinical Presentation

Oral cavity – nonhealing ulcers on the floor of the mouth, tongue, buccal mucosa and hard palate; persistent sore throat
Hypopharynx – hoarseness, dysphagia, otalgia, enlarged cervical nodes
Oropharynx – sore throat, otalgia, odynophagia, chronic dysphagia
Larynx – hoarseness, shortness of breath; supraglottic (neck mass)
Nasopharynx – usually late symptoms of bleeding, obstruction, cranial nerve palsy; otitis media unresponsive to antibiotics
Salivary glands – swelling, adenopathy
See Thyroid Cancer for information on thyroid tumors

Prevention

Benefit of HPV vaccination in reducing head and neck cancer risk is unknown

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

Test name: Human Papillomavirus (HPV) Panel by in situ Hybridization, Paraffin

ARUP #: 2002893

Methodology: In situ Hybridization

Use:

Use for oropharyngeal carcinomas; indicative of better prognosis

Test name: Squamous Cell Carcinoma Antigen, Serum

ARUP #: 0081054

Methodology: Quantitative Enzyme-Linked Immunosorbent Assay

Use:

May be used sequentially (pre- and post-surgery) to follow tumor progression (increasing SCC antigen concentrations are associated with tumor stage progression)

Limitations:

Elevated in patients with a variety of cancers

Not intended for use in diagnosis

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

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

Test name: EGFR Gene Amplification by FISH

ARUP #: 0049234

Methodology: Fluorescence in situ Hybridization

Use:

May be a prognostic marker; may also be useful in establishing treatment regimen

Limitations:

Role in management of head and neck SCCs not well established

Test name: ERBB2 (HercepTest®) with Reflex to ERBB2 (HER-2/neu) Gene Amplification by FISH if 2+ or 3+

ARUP #: 0049172

Methodology: Immunohistochemistry

Use:

May be associated with improved prognosis

Test name: Epstein-Barr Virus, Quantitative PCR

ARUP #: 0051352

Methodology: Quantitative Polymerase Chain Reaction

Use:

Monitor disease progression

Test name: Epstein-Barr Virus (EBV) By in situ Hybridization, Paraffin

ARUP #: 2002902

Methodology: In situ Hybridization

Use:

Use for nasopharyngeal carcinoma

Test name: p16 by Immunohistochemistry

ARUP #: 2004064

Methodology: Immunohistochemistry

Use:

Histologic prognosticator for oropharyngeal carcinomas; indicative of better prognosis

Additional Tests Available

Test name: Lipid Associated Sialic Acid

ARUP #: 0080467

Methodology: Quantitative Spectrophotometry

Comments:

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)