Human Papillomavirus and P16 in the Etiology and Pathogenesis of Oropharyngeal Squamous Cell Carcinoma
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1 Objectives Human Papillomavirus and P16 in the Etiology and Pathogenesis of Oropharyngeal Squamous Cell Carcinoma Joaquín García, M.D. Department of Laboratory Medicine and Pathology Division of Anatomic Pathology Mayo Clinic, Rochester, MN USA Identify the key principles and events related to HPV in the pathogenesis of OSCC Recognize indications for HPV testing in OSCC Interpret various clinical assays designed for HPV detection in OSCC Understand the strengths and limitations of current assays available for HPV testing in OSCC Outline I. Oropharyngeal Squamous Cell Carcinoma (OSCC) in Review II. The Role of Human Papillomavirus (HPV) in OSCC III. Indications for HPV Testing in OSCC IV. Interpretation of HPV Testing in OSCC Oropharyngeal Squamous Cell Carcinoma in Review V. HPV Testing in OSCC in Review 1
2 Oropharynx Anatomy Epidemiology of OSCC Demographics Nasopharynx Oropharynx Laryngopharynx Epidemiology of OSCC Incidence Management Strategies of OSCC Surgery Radiotherapy Chemotherapy Targeted Therapy 2
3 Human Papillomavirus (HPV) The Role of HPV in Oropharyngeal Squamous Cell Carcinoma HPV in OSCC Oncogenesis Genome HPV in OSCC Oncogenesis Pathways E6 E7 E6 E7 L1 E1 Rb p53 L2 E5 E2 E4 p16 INK4 Proliferation 3
4 HPV in OSCC Oncogenesis Detection Indications for HPV Testing in Oropharyngeal Squamous Cell Carcinoma 50 80% Prognostic Prognostic HPV DNA ISH HPV DNA ISH 4
5 Prognostic Diagnostic p16 Immunostain H&E p16 Immunostain HPV DNA ISH Interpretation of HPV Testing in Oropharyngeal Squamous Cell Carcinoma Detection Interpretation Significance 5
6 Polymerase Chain Reaction (PCR) Detection Interpretation Significance Sensitive Specific Histologic Correlation Availability DNA In Situ Hybridization E6/E7 messenger ribonucleic acid (mrna) Sensitive Specific Histologic Correlation Availability Sensitive Specific Histologic Correlation Availability 6
7 P16 Immunohistochemistry Sensitive Specific Histologic Correlation Availability HPV Testing in Oropharyngeal Squamous Cell Carcinoma in Review Joaquín García, M.D. Department of Pathology Mayo Clinic 200 1st Street SW Rochester, MN (507) (office) (507) (fax) 7
8 References References 1. Jo VY, Mills SE, Cathro HP, Carlson DL, Stelow EB. Low-grade sinonasal adenocarcinomas: the association with and distinction from respiratory epithelial adenomatoid hamartomas and other glandular lesions. Am J Surg Pathol. 2009;33: Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst May 3;92(9): Lewis JS, Jr, Thorstad WL, Chernock RD, Haughey BH, Yip JH, Zhang Q, El-Mofty SK. p16 positive oropharyngeal squamous cell carcinoma: an entity with a favorable prognosis regardless of tumor HPV status. 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