1. 2015 Wisconsin Comprehensive Cancer Control Summit Aligning Partners, Priorities, and the Plan HPV-Related Head and Neck Squamous Cancers May 28, 2015 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)

2. The Nature 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 –Most women infected with HPV do not develop cervical cancer. Genital warts have a high recurrence rate after treatment

3. Within 1 Year1-5 Years Up to Decades Initial HPV Infection Persistent Infection CIN 2/3 Cancer CIN 1 Cleared HPV Infection Natural History of HPV Infection

4. Pharyngeal Anatomy

5. Traditional Presentation of Head and Neck Cancers Smoker-Drinker older male Painful mass, ulcer, nodule Change in longstanding leukoplakia Articulation change Otalgia Bleeding Weight loss Dysphagia Airway obstruction with stridor Hoarseness Neck mass

6. Natural History of Oropharyngeal Cancer Local invasion Regional metastases develop early –Bilateral –Levels II, III, IV, V

7. Etiologies and Associations – 1990 Tobacco Alcohol EBV (nasopharyngeal cancers) Genetics Diet (Vitamin A, C, E deficiency) Dental irritation; poor oral hygiene

8. Arch Otolaryngol Head Neck Surg 1998;124:951-962 Oral Cavity Oropharynx Lip Hypopharynx Nasopharynx Larynx

9. Oropharynx Cancer Patients 1881 1996 2010

10. 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)

11. Incidence of and Mortality from Oral Cavity and Pharyngeal Cancer 1975-2002 J Natl Cancer Inst 2006; 98:87

12. 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

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

14. 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

15. Association between oral HPV infection and oropharyngeal cancer OP cancer significantly associated with –Oral HPV-16 infection (OR 14.6) –Seropositivity for the HPV-16 L1 capsid protein (OR 32.2) –Oral infection with any of 37 types of HPV (OR 12.3) 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

16. 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)

17. PET Scan: Tumor Response April to October 2011

18. April 2010  June 2011

19. May 2006  December 2009

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

21. 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

22. Etiologies and Associations – 2015 Tobacco Alcohol Human Papilloma Virus (especially HPV-16) EBV (nasopharyngeal cancers) Genetics Diet (Vitamin A, C, E) Dental irritation; poor oral hygiene

23. Cost-Effectiveness of Male Vaccination Assuming 99% vaccine efficacy and 70% uptake –0.05 more QALYs –Saved $145 per individual Assuming 50% vaccine efficacy and 50% uptake –0.023 more QALYs –Saved $42 per individual “The results indicated that HPV4 in males may potentially save between $8 and $28 million for the theoretical cohort of 192,940 over its lifetime” Donna M. Graham DM, et al., A cost-effectiveness analysis of HPV vaccination of boys for the prevention of oropharyngeal cancer, Cancer 2015, Online: 13 APR 2015 (DOI: 10.1002/cncr.29111)

24. 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

25. Take Home Points HPV-Related Head and Neck SCC of the Oropharynx Associated with increased exposure to oral sex and increased number of partners Often presents in men in their 50’s and 60’s Often presents with Stage IV disease Increasing in prevalence MUCH better outcomes than non-HPV cancers Treated with RT and platinum-based CTX Clinical trials are investigating whether “treatment de-escalation” might be possible Immunize the boys, too

26. Comments or questions bcampbell@mcw.edu (414) 805-5583 Reflections in a Head Mirror www.froedtert.com/reflections