Head and neck cancer

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

2. 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.

3. Head and Neck Cancer has three major subdivisions: • Oral Cancer • Laryngeal Cancer • Nasopharyngeal Cancer.

4. 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

5. 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 Risk Factors for Head and Neck Cancer

6. Possible Occupational Risks for Head and Neck Cancer • Woodworking • Leather manufacturing • Nickel refining • Textile industry • Radium dial painting

7. Hoarseness Erythroplasia Referred otalgia Persistent sore throat Epistaxis Nasal obstruction Serous otitis media Neck mass Non-healing ulcer Dysphagia Submucosal mass Warning Signs of Head and Neck Cancer Not all cancers present with symptoms at early stages!

8. 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

9. Five-Year Survival Rate for Oral Cavity and Pharynx Cancer Stage at Diagnosis

10. 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.

11. 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

12. Biomarkers utilized in this study

13. Projection Pursuit Technique

14. 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.

15. 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.

16. 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.

17. Head and Neck Cancer Link to chronic infection • HPV • Epstein Barr virus

18. Human Papillomavirus (HPV) • DNA virus • Preferentially infect squamous epithelial cells • >100 genotypes • ≥40 genital HPV types

19. 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

20. Lifestyle Factors “Genes load the gun.Lifestyle pulls the trigger” Dr. Elliot Joslin

21. 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