The HPV Cancer Epidemic: Why We Must Vaccinate Our Boys Acadiana Potpourri Lafayette, Louisiana August 19, 2017

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1 The HPV Cancer Epidemic: Why We Must Vaccinate Our Boys 2017 Acadiana Potpourri Lafayette, Louisiana August 19, 2017 Erich M. Sturgis, MD, MPH Professor, Department of Head & Neck Surgery and Department of Epidemiology Christopher & Susan Damico Chair in Viral Associated Malignancies Administrative Leader HPV-Related Cancers Moon Shot Program Director MD Anderson Oropharynx Program No conflicts, disclosures, or off-label

2 2008 Nobel Prize in Physiology or Medicine Harold zur Hausen, M.D.

3 International Burden of HPV Cancer (cervical cancer) 2015: 1 in 6 live in Africa 2050: 1 in : 2 in : 1 in 6 live in Africa 2050: 1 in : 2 in 5 WHO, IARC globocan.iarc.fr

4 ~40 HPV Types Mucosal sites of infection ~ 80 HPV Types Cutaneous sites of infection High risk (oncogenic) HPV 16, 18 most common Low risk (non-oncogenic) HPV 6, 11 most common Oropharyngeal Cancers Cervical & Anogenital Cancers Cancer Precursors Laryngeal Papillomas Genital Warts Low Grade Cervical Disease Cutaneous Warts CDC HPV Slide Deck cdc.gov/hpv/hcp/speaking

5 HPV Genital Infection Most females & males will be infected in the US: 80 million currently infected (14M new/yr) most without symptoms most common in teens & early 20s HPV Throat Infection 5% of women & 15% of men currently infected most without symptoms highest rates in 50s J Natl Cancer Inst 2013;105: and JAMA 2012;307(7):

6 Oral HPV prevalence by age

7 HPV Infection & Progression to Cancer Schematic NORMAL MUCOSA

8 Mechanism of HPV Driven Carcinogenesis C.T. Allen, et al. Laryngoscope 2010

9 J Natl Cancer Inst 2013 Total (N=38,793) ~60,000 3, % % 1, % 1, % Men (N=15,793) 1, % % Women (N=23,000) ~27,000 ~33,000 3, % 3, % 3, % 11, % 5, % 15, % 12, % 11, % Oropharynx Anus Cervix Vagina Vulva Penis

10 Crisis in America APC: +5-10% +5-10% +3% Penis < 1/100,000 ~0% SEER.cancer.gov Chaturvedi et al. JCO 2008.

11 Newly Diagnosed-Untreated Cases Presenting to MD Anderson Each Year 350 Number of Cases Oropharynx Cervix Anus Vulva Penis

12 Average annual number of cancers attributable to HPV, overall and by sex U.S., Total (N=30,700) 2, % % % 1, % Men (N=11,600) % Women (N=19,200) 2, % % 2, % 3, % 10, % 5, % 11, % 9, % 10, % Oropharynx Anus Cervix Vagina Vulva Penis Viens LJ, et al. MMWR 2016;65:661-6

13 Head & Neck Cancer Nose/Paranasal Sinuses Nasopharynx Oral Cavity (mouth) Oropharynx tonsil base of tongue or lingual tonsil Hypopharynx Larynx (voicebox) Thyroid Cancer, Melanoma & Skin Cancer, Salivary Gland Cancer

14 Oropharyngeal Cancer Typical Presentation Middle-aged White Male Nonsmoker or Former Smoker Middle to High Socioeconomic No Throat Symptoms Neck Mass (ie Stage IV) Pytynia KB, et al. Oral Oncology 2014;50:

15 Trends in Cancer Incidence & Number Oropharynx vs. Cervix Chaturvedi AK, et al. JCO 2011.

16 Cervix Oropharynx Median Age at Presentation: ~45yo ~55yo

17 Prevention of OPC through Screening No precursor lesion No screening test 5% increase in incidence each year Beneficial effects of vaccination will take decades

18 Screening for HPV+ Oropharyngeal Cancer Cervical cancer incidence decreased due to cytology screening (Pap test) Can we use similar strategy to screen for HPV+ OP cancer? Unlikely due to limitations in sampling the oropharynx epithelium Antibodies to HPV E antigens to identify a high-risk group Cancer Prev Res; 4(9) September 2011

19 Anderson KS, et al. Oral Oncol and Dahlstrom KR et al. Cancer (in press). RLU ratio NS E1 RLU ratio NE2 RLU ratio CE2 ** ** ** NS NS Control Non-OPC p16+opc Control Non-OPC p16+opc Control Non-OPC p16+opc E4 ** E5 E6 ** RLU ratio NS RLU ratio NS ** RLU ratio NS Control Non-OPC p16+opc Control Non-OPC p16+opc Control Non-OPC p16+opc Sample Sizes: Controls = 782 Non-OPC = 153 P16+ OPC = 348 P16- OPC = 30 RLU ratio NS E7 Control Non-OPC p16+opc RLU ratio L1 ** ** ** NS Control Non-OPC p16+opc RLU ratio NS L2 Control Non-OPC p16+opc Binary Classifier: Sensitivity 83% Specificity 99% AUC 91% Adj. Odds Ratio= 453 ( )

20 HOUSTON: Hpv-related Oropharyngeal & Uncommon cancers Screening Trial Of men Phase 1: Cross-sectional TMC-CRU & MDA-CTRC Phase 2: Longitudinal study 5 years at MDA 5,000 Men years old Houston consent (phase Region 1) Pre-screen questionnaire Demo & behavioral questionnaire Informed consent (phase 1) Demo Blood & for behavioral serology (ASU) questionnaire Oral rinse: HPV16 DNA Blood for serology (ASU) Ab Ab- Additionally: subjects not already selected for screening with oral rinse positive for HPV16 DNA Informed Consent (phase 2) Oral PremalignancyClinic exam, NBI, OCT, and swab each tonsil & BOT Ultrasound neck lymph nodes and transcervical tonsil/bot view Anoscopy Cytology, HPV DNA, and HRME Penile exam with HPV DNA and UA Blood Draw immune response assays (sero & Tcell) Serial screen (every 6 mo x 5 yrs) Oral Premalignancy Clinic exam, NBI, OCT, and swab each tonsil & BOT Ultrasound neck lymph nodes & transcervical tonsil/bot view Serial Screen Blood Draw (every 12 mo x 5 years) immune response assays (serology & T cell) Oral rinse: HPV16 DNA 4,750-4,850 Ab- Annual health status survey

21 Are you at risk of HPV-related Throat Cancer?

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23 CDC HPV Slide Deck cdc.gov/hpv/hcp/speaking

24 HPV Prophylactic Vaccines Recombinant L1 capsid proteins that form virus-like particles Non-infectious and non-oncogenic Produce higher levels of neutralizing antibody than natural infection HPV Virus-Like Particle Safe Effective Long lasting CDC HPV Slide Deck cdc.gov/hpv/hcp/speaking

25 HPV Vaccines Licensed in U.S. Bivalent 2vHPV (Cervarix) Quadrivalent 4vHPV (Gardasil) 9-Valent 9vHPV (Gardasil 9) Manufacturer GSK Merck Merck HPV Types Included Contraindications Dose Schedule 16, 18 6, 11, 16, 18 Hypersensitivity to latex* 3 dose series: 0, 1, 6 months Hypersensitivity to yeast 3 dose series: 0, 2, 6 months 6, 11, 16, 18, 31, 33, 45, 52, 58 Hypersensitivity to yeast 2 (3) dose series: 0, 12 months Adapted from Petrosky et al. MMWR ~70% of Cervical Cancers, & ~90% of HPV+ OP & Anal Cancers Genital Warts, ~70% of Cervical Cancers, & ~90% of HPV+ OP & Anal Cancers Genital Warts, ~85% of Cervical Cancers, & ~90% of HPV+ OP & Anal Cancers

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27 HPV Vaccine Recommendation Girls and Boys can start HPV vaccination at age 9 Should finish HPV vaccine 2-dose series by 13 th birthday Catch-up Vaccination (3-doses): girls years (21) old who have not started or finished CDC HPV Slide Deck cdc.gov/hpv/hcp/speaking

28 63% 50% 42% 2 doses: 52% 39% 28%

29 HPV vaccine 2 dose: 3dose(completion): females males females males National 52% 39% 42% 28% Louisiana 53% 39% 39% 31% SEER.cancer.gov

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31 MD Anderson The University of Texas MD Anderson Cancer Center HPV-Related Cancers MOON SHOT

32 HPV-Related Cancers Moon Shot Vision Evolution from HPV Strategic Planning Meeting (August 2014) Prevention and Screening: Eradicate HPV-associated cancers through vaccination and novel screening Toxicity and Recurrence/Metastasis: Reduce suffering of patients with HPV-associated cancers through innovative therapies

33 MD Anderson HPV-Related Cancers Moon Shot (Administrative Leader- Erich M. Sturgis) Flagship #1 Prevention & Screening Policy & Education (Lois M. Ramondetta) Screening (Kathleen M. Schmeler) Cancer Prevention and Control Platform: Health Policy Government Relations Professional Education Public Education Flagship #2 Discovery Genomics (Curtis R. Pickering) Target Discovery (Faye M. Johnson) Platforms: Cancer Genomics Lab Institute for Applied Cancer Sciences Flagship #3 Immunotherapy & Novel Trials Rare Tumors (Cathy Eng) Cervix (Michael M. Frumovitz) Oropharynx (Maura L. Gillison) Platforms: Center for Co-Clinical Trials Immunotherapy Oncology Research Biologics & Immunotherapy Translation

34 Flagship 1 Goal 1: Increase Vaccination Lois Ramondetta (Melanie Wong) Information Transfer Demonstration Project Clinic-based provider training 12,468 age-eligible youth, 8/ ,196 age-eligible youth, 8/2017

35 Flagship 1 Goal 1 (cont) Increase Vaccination Environmental Scan Report HPV resource took kit Nov 2015 meeting HPV Consensus Statements Jan 2016 and Jan 2017 Senate Bill 200 DSHS Strategic Plan Dec 2016 Long-range Economic Modeling, UT SPH Inform policy makers Bring Expertise on HPV Strategic Plan Efforts to Other States

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37 Flagship 1 Goal 2: Improve access to cervical cancer screening in underserved populations Project HRME, ECHO/Telementoring Low-cost technology development program for (with screening CPC underserved Platform) populations (collaboration with Rice University) Rio Grande Valley - bi-weekly (cervix) Launched in El Salvador and Brazil Screened ~12,000 women Doubled number of providers trained in colposcopy/leep 587 patients enrolled in El Salvador Africa 200 patients (Mozambique enrolled and in Zambia) Brazil monthly (cervix and H&N) collaboration with 3 sister institutions in Brazil Hands-on clinical and surgical training workshops Latin America monthly (cervix) 10 countries in Central and South America

38 Flagship 1 Goal 3 Develop new screening for non-cervical cancers PANDA Study (Prevalence of ANal DysplasiA) Anoscopy screening in patients with CIN II/III or Ca Screening (Schmeler, Messick, Trial and of Milbourne) Men: HPV-related Oropharyngeal and Uncommon Cancers Sample size = 500 patients The HOUSTON Study ClinicalTrials.gov identifier: NCT Study sites: MD Anderson and LBJ Colposcopy clinics 30 accrued; 2 high-risk Anoscopy with anal Pap test and anal HPV testing Abnormal findings/results referred to colorectal surgery (Messick) 65 thus far (10% with high grade dysplasia)

39 Conclusions HPV cancer epidemic in men: Oropharyngeal and Anal HPV vaccination is imperative: Further Delay = Exponential Costs & Suffering Without novel screening/treatment of pre-malignancy: 30 years of increasing incidence

40 MD Anderson Thank You