Transcript Head and Neck Cancer - University of Pittsburgh

Head and neck cancer
Faina Linkov, PhD
Research Assistant Professor
of Medicine
University of Pittsburgh Cancer
Institute
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.
Head and Neck Cancer has three
major subdivisions:
• Oral Cancer
• Laryngeal Cancer
• Nasopharyngeal Cancer.
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
Risk Factors for
Head and Neck Cancer
Tobacco Products:
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Smoking Tobacco
Cigarettes
Cigars
Pipes
Chewing Tobacco
Snuff
Ethanol Products
Chemicals:
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Asbestos
Chromium
Nickel
Arsenic
Formaldehyde
Other Factors:
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Ionizing Radiation
Plummer-Vinson Syndrome
Epstein-Barr Virus
Human Papilloma Virus
Possible Occupational Risks
for Head and Neck Cancer
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Woodworking
Leather manufacturing
Nickel refining
Textile industry
Radium dial painting
Warning Signs of Head and Neck Cancer
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Hoarseness
Erythroplasia
Referred otalgia
Persistent sore throat
Epistaxis
Nasal obstruction
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Serous otitis media
Neck mass
Non-healing ulcer
Dysphagia
Submucosal mass
Not all cancers present with symptoms
at early stages!
Factors Delaying the Diagnosis of
Head and Neck Cancers
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Patient procrastination in seeking medical
attention
Physician delay in diagnosis
Patient remains asymptomatic for a prolonged
period
Five-Year Survival Rate for Oral
Cavity and Pharynx Cancer
70
60
50
40
Caucasian
African-American
30
20
10
0
Localized
Regional
Stage at Diagnosis
Distant
Research in Head and Neck
Cancer Biomarkers at UPCI
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.
Luminex xMAP®
Technology
• Bead-based assay
• 1-100 analytes/well
flow-based
LUMINEX
array reader
• Small sample volume
• >1000 sample/day
• Reproducible results
• Cost effective
Biomarkers utilized in this study
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
Projection Pursuit Technique
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 25marker panel. Cross-validation test, 55/45 random split, 100 runs.
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.
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, MIP1, IL-7, IL-17, IL-1R, IL-2R, G-CSF,
mesothelin, IGFBP-1, E-selectin, cytokeratin
(CK)19, V-CAM, and CA-125.
Head and Neck Cancer
Link to chronic infection
• HPV
• Epstein Barr virus
Human Papillomavirus (HPV)
• DNA virus
• Preferentially
infect squamous
epithelial cells
• >100 genotypes
• ≥40 genital HPV
types
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
Lifestyle Factors
“Genes load the gun.
Lifestyle pulls the trigger”
Dr. Elliot Joslin
Acknowledgement:
Luminex Core Facility
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Anna Lokshin, PhD
Alex Lisovich, PhD
Zoya Yurkovetsky, PhD
Adele Marrangoni, BS
Lyudmila
Velikokhatnaya, MS
• Matt Winnans, BS
• Bryan Nolen, MS