5/6/2015. HPV-Related Head and Neck Cancer ANATOMY MUCOSA. James V. Zirul, D.O. Combined ACP and AKOMA Conference 09.Apr.2015 ORAL CAVITY NASOPHARYNX

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1 HPV-Related Head and Neck Cancer James V. Zirul, D.O. Combined ACP and AKOMA Conference 09.Apr.2015 ANATOMY ORAL CAVITY Anterior 2/3 tongue, retromolar trigone area (posterior to the molars) and hard palate NASOPHARYNX Nasal choana to the upper portion of the posterior soft palate (adenoids) OROPHARYNX Posterior pharynx and tongue base including the palatine tonsils HYPOPHARYNX Inferior to the palatine tonsils, lateral and posterior walls to the epiglottis MUCOSA Lining of the buccal mucosa, floor of mouth, posterior pharynx, ventral tongue, floor of mouth and hypopharynx Non-keratinized stratified squamous epithelium Dorsal tongue, hard palate and attached gingiva Keratinized stratified squamous epithelium Palatine tonsils, lingual tonsils and adenoids Comprised of large pads of lymphoepithelial tissue attached to or surrounded by squamous epithelium (Waldeyer s Ring) 1

2 HPV vs NON-HPV SQUAMOUS CELL CANCER NON-HPV CANCERS 2004 to 2008 world-wide 50% decrease Tobacco counseling and education HPV POSITIVE SQUAMOUS CELL CANCER (SCC) 2004 to 2008 world-wide 225% increase Specific testing now available HPV vs NON-HPV SQUAMOUS CELL CANCER HPV POSITIVE SEXUALLY TRANSMITTED DISEASE HPV 16 PRIMARY VIRUS GENOTYPE DEMOGRAPHICS Males 5 to 6 times more likely than females Predominantly Caucasian Age generally 40 to 60 years old Relatively little tobacco or alcohol use Oral or vaginal sex with greater than six partners HPV and Sex INCREASED RISK OF CANCER Partner with HPV positive cervical cancer HPV genotype 16, 18, 51, 53 Personal history of immune suppressive disease Personal history of HPV positive cancer HPV 16 PRIMARY HPV VIRUS FOR OROPHARYNGEAL CANCER 1% seropositive HPV 16 will develop 25% head and neck cancers HPV 16 positive LENGTH OF TIME FROM INFECTION TO DIAGNOSIS Estimated 10 to 20 years after exposure 2

3 CARCINOGENESIS NON-HPV CANCER Broad Field exposure to carcinogens Long-term exposure - tobacco, alcohol, betel nuts Oncoprotein cell cycle deregulation in the basal layer of the mucosa secondary LOCALIZED HPV 16 SQUAMOUS CELL CANCER Located in small areas of deep lymphoepithelial folds Mediated by viral oncoproteins with essentially the same cell cycle deregulation of the basal layer of the mucosa in a small area of mucosa Small aggressive primary tumors with large metastatic lymph nodes END RESULT Expression of p16 protein used as a marker for identifying HPV 16 tumors PRESENTATION STAGING T small, N - large Primary site Asymptomatic Measuring 0.5 cm in early stages of disease HPV 16 SCC Most initially present with cervical lymphadenopathy mid to upper neck Rapid growth of lymphadenopathy Nodes under 2.0 cm hard to palpation and mobile Larger nodes fixed to deep tissue Usually unilateral, sometimes bilateral LOCATION HPV CARCINOGENESIS IN LYMPHOEPITHELIAL TISSUE Palatine tonsil or lingual tonsils (tongue base) HPV POSITIVE TUMORS IN NON-LYMPHOEPITHELIAL AREAS Primarily located in close proximity to the palatine and lingual tonsils Exceptions NASOPHARYNGEAL CARCINOMA Viral-induced Epstein Barr virus not HPV. 3

4 HISTORY Complaint of pain in the throat or tonsil or tongue base area in advanced disease Rapid onset of lymphadenopathy Social history of tobacco and alcohol use Sexual history Initial exposure may pre-date current relationship EXAMINATION Evaluation of the mouth mucosa of the lips, buccal mucosa, floor of mouth, ventral tongue, anterior tongue, soft palate, hard palate and palatine tonsils PALPATION Neck, parotid and submandibular glands, anterior tongue, tongue base and palatine tonsils NASOLARYNGOSCOPY Evaluation nasopharynx and upper airway to the glottis CT NECK WITH CONTRAST Identify cervical lymphadenopathy and related soft tissue Establishes baseline for staging and treatment Cystic appearing cervical lymphadenopathy secondary to rapid growth ULTRASOUND-GUIDED NEEDLE BIOPSY Cytology epithelial cells squamous cell cancer unless proven otherwise p16 protein positive staining positive HPV 16 cancer 4

5 IMAGING CT scan neck with contrast Initial study Relationship with other soft tissue structures and establishes a baseline for staging and treatment Ultrasound Ultrasound-guided needle biopsy Cytology assessment may be difficult without adequate history Mention of epithelial cells requires further study Squamous cell cancer unless otherwise proven SURGERY Tonsillectomy with multiple biopsies of the tongue base or lingual tonsillectomy Esophagoscopy Bronchoscopy Open biopsy cervical lymph node DIAGNOSIS HPV-related SCC Generally poorly-differentiated Cystic-appearing cervical lymphadenopathy secondary to rapid growth p16 protein staining pathological confirmation of HPV cancer Polymerase Chain Reaction (PCR) expensive 5

6 TREATMENT COMBINED CHEMOTHERAPY AND RADIATION Cisplatin Cetuximab Monoclonal antibody against epidermal growth factor receptor SURGERY Robotic tongue-base surgery Neck dissection PREVENTION Quadrivalent vaccine HPV genotypes 6, 11, 16, 18 Bivalent vaccine HPV genotypes 16, 18 6