Head and neck cancer Faina Linkov, PhD Research Assistant Professor of Medicine University of Pittsburgh Cancer Institute.

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: 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

Possible Occupational Risks for Head and Neck Cancer

Woodworking Leather manufacturing Nickel refining Textile industry Radium dial painting

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!

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

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

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

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

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

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 25-marker 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, 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.

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

“Genes load the gun.Lifestyle pulls the trigger”

Dr. Elliot Joslin

Lifestyle Factors

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