1. Cancer of the Head and Neck and HPV Infection Andrew Urquhart MD, FACS Dept. Otolaryngology/Head and Neck Surgery Marshfield Clinic

2. Disclaimer “I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity”. “I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.”

3. OBJECTIVES Information regarding cancer of the head and neck, including the oropharynx. Understand the anatomical areas involved and clinical presentation. Bring awareness of the role HPV has in these respective cancers. Highlight the changing demographics of the disease. Understand the changing treatment options for cancer of the oropharynx. The importance of HPV vaccination in adolescents.

4. Introduction

6. 41,000 cases of SCCA Head and Neck annually. Increase in HPV related SCCA Oropharynx 1973-2004 (annual percentage change 0.80 annually). Decline in non HPV related head and neck cancer. Mean age at diagnosis for OSSC has declined. Proportion has increased amongst white males.

7. Over the last 25 years there has been a shift to organ preservation treatment instead of primary surgery. Started with larynx preservation (VA trial). Primary treatment now chemotherapy with Radiotherapy. Chemotherapy (cisplatin: radio sensitizer) Improved local control but increased morbidity.

8. Significant morbidity associated with treatment including severe mucositis, pain, dysphagia, xerostomia, dental caries. Recent improvements including IMRT and salivary sparing fields has resulted in improved tolerance and less side effects.

9. Oropharynx Anatomy Rich lymphatic supply. Difficult to examine and visualize. Vague symptoms, “Globus sensation”. Often present with a single or multiple lymph nodes upper neck.

10. HPV USA, HPV infection in OSCC increased from 16% (1984-1989) to 71.7% (2000 – 2004). Incidence of HPV related OSCC will surpass incidence of cervical cancer 2020.

11. HPV + and - rates IncidenceRateIncidenceRate

13. Carcinoma Oropharynx (OSCC) Generally presents with more advanced disease. Many patients have never smoked. TNM staging does not work for HPV +. NCCN Guidelines. Reality any T or any N = stage 3. Systemic metastasis = Stage 4. Patients do better.

16. Examination of upper aero digestive tract. CT neck. Primary may not be identified. Fine needle biopsy. PET/CT.

17. Direct laryngoscopy, esophagoscopy and biopsy with tonsillectomy. Unknown primary (usually tonsil or tongue base).

21. NCCN Guidelines Stage 1 and 2 disease : surgery. Stage 3 and 4 disease : primary chemo radiotherapy with surgical salvage. PET/CT scan 12 weeks after treatment. If scan negative > 90% chance of cure. Over treatment with increased morbidity. Trend towards primary surgery (including robot). Current studies involving DE intensifying treatment (ECOG 3311).

22. Overall survival (OS) CA oropharynx stage 3 and 4 is 95% (HPV+) vs 62% (HPV -) (p=0.005). Progression free survival is 86% (HPV +) vs 53% (HPV-) (p=0.05) at 2 years. HPV positive tumor status independently associated with a reduced mortality risk after controlling for age, tumor stage and comorbidities.

23. Risk is 200 fold if HPV infection. 5 fold higher HPV rate in Men than women. Distinct demographic profile. Despite favorable initial response up to 30% HPV related cancers experience recurrence.

24. Epidemiology Prevalence of oral HPV infection in general population 4.5% (1.3% for HPV16). Bimodal distribution. Prevalence higher in men than women. Incidence of infection increasing in males, decreasing in females.

25. SUMMARY 41,000 cases of SSCA head and neck in USA annually, 1/3 oropharynx. Majority of oropharyngeal cancers are HPV related and increasing. HPV related oropharyngeal cancer incidence is increasing in males (epidemic) at a younger age. Morbidity associated with treatment is significant. Vaccination!