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Head and neck cancer
Faina Linkov, PhD
Research Assistant Professor of Medicine
University of Pittsburgh Cancer Institute
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What is head and neck cancer?
Head and Neck Cancer is a group
of cancers that includes tumors in several areas above the collar
bone.
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Head and Neck Cancer has three major subdivisions:
• Oral Cancer
• Laryngeal Cancer• Nasopharyngeal Cancer.
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Head and Neck Cancer
Squamous cell carcinoma of the head and neck (SCCHN) occurs in 50,000 new cases annually in the US,
resulting in over 13,000 deaths each year
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Risk Factors for Head and Neck Cancer
Tobacco Products: Smoking Tobacco Cigarettes Cigars Pipes Chewing Tobacco Snuff
Ethanol Products
Chemicals: Asbestos Chromium Nickel Arsenic Formaldehyde
Other Factors: Ionizing Radiation Plummer-Vinson Syndrome Epstein-Barr Virus Human Papilloma Virus
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Possible Occupational Risks for Head and Neck Cancer
Woodworking Leather manufacturing Nickel refining Textile industry Radium dial painting
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Warning Signs of Head and Neck Cancer
Hoarseness Erythroplasia Referred otalgia Persistent sore throat Epistaxis Nasal obstruction
Serous otitis media Neck mass Non-healing ulcer Dysphagia Submucosal mass
Not all cancers present with symptoms at early stages!
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Factors Delaying the Diagnosis of Head and Neck Cancers
Patient procrastination in seeking medical attention
Physician delay in diagnosis Patient remains asymptomatic for a prolonged
period
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Five-Year Survival Rate for Oral Cavity and Pharynx Cancer
0
10
20
30
40
50
60
70
Localized Regional Distant
Caucasian
African-American
Stage at Diagnosis
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Concentrations of 60 cytokines, growth factors, and tumor antigens were
measured in the sera of 116 SCCHN patients prior to treatment (active disease
group), 103 patients who were successfully treated (no evidence of
disease, NED, group), and 117 smoker controls without evidence of cancer.
Research in Head and Neck Cancer Biomarkers at UPCI
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Luminex xMAP® Technology
• Bead-based assay
• 1-100 analytes/well
• Small sample volume
• >1000 sample/day
• Reproducible results
• Cost effective
flow-based LUMINEX
array reader
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Biological groups Proteins
Cytokines/Chemokines
IL-6, IL-8, TNF-, IL-12p40, IL-2R, IL-1, IL-2, IL-4, IL-5, IFN-, IL-13, IL-15, IFN-, IL-1, IL-7, Fas, FasL, MIP-3, MIP-3b, MIF, MCP-1, IL-10, IL-17, IL-1Ra, DR5, TNF-RI, TNF-RII, EOTAXIN, MIP-1, MIP-1, IP-10, MIG, RANTES
Growth/angiogenic factors
EGF, VEGF, FGF-b, G-CSF, HGF, GM-CSF, ErbB2, EGFR, IGFBP-1
Proteases Kallikrein-8, Kallikrein-10, MMP-2, MMP-3
Cancer Antigens CA-153, CEA, CA 19-9, CA-125, AFP, CA 72-4
Adhesion molecules sE-Selectin, sV-CAM, sICAM
Other markers Cytokeratin-19, HCG, MPO, tPAI-1, Mesothelin IgY
Biomarkers utilized in this study
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Projection Pursuit Technique
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Head and Neck Cancer (ROC curve)Classification of head and neck cancer (n=116) vs. no evidence of disease group (n=103), and healthy smokers control utilizing the 25-marker panel. Cross-validation test, 55/45 random split, 100 runs.
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Sensitivity refers to the fraction of patients with the disease correctly identified as positive by the test.
Specificity refers to the fraction of patients without the disease correctly identified as negative by the test.
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The multi-marker panel offering the highest diagnostic power was comprised of 25
biomarkers, including:
EGF, EGFR, IL-8, tPAI-1, AFP, MMP-2, MMP-3, IFN-, IFN-, IP-10, RANTES, MIP-
1, IL-7, IL-17, IL-1R, IL-2R, G-CSF, mesothelin, IGFBP-1, E-selectin, cytokeratin
(CK)19, V-CAM, and CA-125.
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Head and Neck Cancer
Link to chronic infection
• HPV
• Epstein Barr virus
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Human Papillomavirus (HPV)
• DNA virus
• Preferentially infect squamous epithelial cells
• >100 genotypes
• ≥40 genital HPV types
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Epidemiology of HPV
•The most common STD worldwide
•80% sexually active adults in the US infected with at least one HPV type by age 501
•Peak prevalence during adolescence and young adulthood
•Prevalence declines with age
•HPV 16 is the most common HR type
1. Centers for Disease Control and Prevention. Rockville, Md: CDC National Prevention Information Network; 2004
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“Genes load the gun.Lifestyle pulls the trigger”
Dr. Elliot Joslin
Lifestyle Factors
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Acknowledgement: Luminex Core Facility
• Anna Lokshin, PhD• Alex Lisovich, PhD• Zoya Yurkovetsky, PhD• Adele Marrangoni, BS• Lyudmila
Velikokhatnaya, MS • Matt Winnans, BS• Bryan Nolen, MS