1. HPV-Related Head and Neck Squamous Cancers Bruce H. Campbell, MD FACS Medical College of Wisconsin MCW Department of Otolaryngology and Communication Sciences MCW Institute for Health and Society (Center for Bioethics and Medical Humanities) 2016 HPV Vaccine Summit: HPV – You are the Key to Cancer Prevention May 12, 2016

2. Financial Relationship Disclosure Statement 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. Learning Objectives that Address the Practice Gaps and may Lead to Change Understand: –Oropharyngeal cancer presentation and basics of treatment –The increasing proportion of oropharynx cancers is related to HPV –HPV vaccination should have an impact on incidence –More men than women are diagnosed with oropharyngeal cancer

4. The Invisible Origins of HPV Infection Genital HPV infection is common in sexually active adults –Majority will have HPV infection at some point –Most will never know Natural history of HPV infection is usually benign –Low-risk HPV types (6, 11) Mild Pap test abnormalities Genital warts –High-risk types HPV types (16, 18) Mild to severe Pap test abnormalities Rarely, cancers of the cervix, vulva, vagina, anus, penis, oropharynx

5. How HPV causes cancer… HPV proteins E6 and E7: Block cell cycle regulation Defeat the cell’s surveillance of “bad” cells Let the cells grow forever Munger K, et al., J Virology 2004; 78(21): 11451-11460

6. Within 1 Year1-5 Years Up to Decades Initial HPV Infection Persistent Infection CIN 2/3 Cancer CIN 1 Cleared HPV Infection Time Course of HPV infections

7. Cancers with Rising Incidence 1999-2008 Pancreas Liver Thyroid Kidney Melanoma Esophageal adenocarcinoma HPV-positive oropharynx Simard, Ca: Cancer J Clinicians (published online: 4 JAN 2012)

8. Pharyngeal Anatomy

9. Natural History and Symptoms of Oropharyngeal Cancer Early nodal spread Sore throat Trouble swallowing Neck mass

10. Oropharynx Cancer Patients 1996 1881 2010

11. WhiteBlackAsianNativeHispanic Male4.4%-0.1%0.7%-0.1%0.3% Female1.9%-0.6%-2.2%NA-0.7% Simard, Ca: Cancer J Clinicians (published online: 4 JAN 2012) HPV-Positive Oropharynx Average Annual Percentage Change (AAPC) Per 100,000

12. Percentage of Oropharyngeal Cancers that are HPV Positive Chaturvedi AK, J Clin Oncol 2011; 29 (32): 4294-4301

13. Wisconsin Oropharynx Cancer Incidence Cases per 100,000 1995-2011 Source: Wisconsin Cancer Reporting System, Office of Health Information Division of Public Health, Department of Health Services, 2014

14. Association between oral HPV infection and oropharyngeal cancer OP cancer significantly associated with –Oral HPV-16 infection (OR 14.6) Sexual activity associated with OP cancer –>25 vaginal partners (OR 3.1) –>5 oral sex partners (OR 3.4) D’Souza NEJM 2007 356:1944-1956

15. Overall Survival Based on Tumor HPV Status Ang, N Engl J Med 2010;363:24-35

16. Risk Stratification Based on HPV, Smoking, Tumor Size, and Nodal Size Ang, N Engl J Med 2010;363:24-35 93 % 71 % 46 % 3-yr OS

17. Management of HPV-Positive Oropharyngeal Cancer Concurrent Platinum-based chemotherapy and radiation therapy Concurrent cetuximab and radiation therapy Surgery with postoperative radiation therapy –Transoral laser microsurgery (TLM) –Transoral Robotic Surgery (TORS)

18. PET Scan: Tumor Response April to October 2011

19. April 2010  June 2011

20. May 2006  December 2009

21. National Immunization Survey Physician Responses on the HPV Vaccine Survey Question20082013 P- value Recommendation for 11- and 12- year olds Strong52%59%.05 Not strong39%33%.05 None or recommendation against7%6%.05 Major barriers to parent compliance Concern about vaccine safety5%18%<.01 Concern about encouraging sexual activity 4%13%<.01 Lack of insurance coverage22%7%<.01 Kempe A, Pediatric Academic Societies (PAS) 2015 Annual Meeting: Abstract 3115.2. Presented April 27, 2015

22. Changes in Practice that Might Narrow the Practice Gaps Head and Neck SCC of the Oropharynx Share with parents and teens: –Immunize boys and girls –HPV-related cancers are associated with increased exposure to oral sex and increased number of partners –HPV-related cancers are increasing in prevalence –Cancers are most common in males in their 50s and early 60s –Symptoms are often subtle –Treatment is effective

23. Comments or questions bcampbell@mcw.edu (414) 805-5583 References: Munger K, et al., J Virology 2004; 78(21): 11451-11460 Simard, Ca: Cancer J Clinicians (published online: 1/4/2012) Chaturvedi AK, J Clin Oncol 2011; 29 (32): 4294-4301 Wisconsin Cancer Reporting System, Office of Health Information Division of Public Health, Wisconsin Department of Health Services, 2014 D’Souza NEJM 2007 356:1944-1956 Ang, N Engl J Med 2010;363:24-35 Kempe A, Pediatric Academic Societies (PAS) 2015 Annual Meeting: Abstract 3115.2. Presented April 27, 2015 Bailey, ASCO Statement: HPV for Cancer Prevention, J Clin Oncol 2016 (Pulished online 4/11/2016)