HPV is ubiquitous. Skin-to-Skin Contact. Most will not develop cancer. By age 50, 80% of women will have acquired a genital HPV infection

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2 Worldwide, HPV causes ~5% of all new cancers occurring in males and females annually Globally, HPVs are responsible for: Virtually 100% of cervical cancers 70% of vaginal cancers 43% of vulvar cancers Almost all cases of genital warts and RRP 88% of anal cancers 50% of penile cancers At least 26% of oropharyngeal cancers HPV is the most common sexually transmitted infection in the United States. More than 6.2 million new infections every year Nearly three-fourths of new infections occur in 15- to 24- year-olds RRP=recurrent respiratory papillomatosis. Forman D et al. Vaccine. 2012;30 suppl 5:F12-F23; Lacey CJ et al. Vaccine. 2006;24 suppl 3:S3/35-S3/ Dunne EF et al. JAMA. 2007;297(8): Skin-to-Skin Contact HPV can spread throughout the anogenital region Condoms only partially effective for prevention Some adolescents found to test positive for vaginal HPV prior to first vaginal sexual intercourse By age 50, 80% of women will have acquired a genital HPV infection HPV is ubiquitous Shew ML et al. J Infect Dis. 2013;207(6): Dunne EF et al. JAMA. 2007;297(8): ; Centers for Disease Control and Prevention. Vaccines and Immunizations. The Pink Book: Course Textbook. 13th ed (2015). Accessed April 11, By age 50, 80% of women will have acquired a genital HPV infection Most will not develop cancer Breast Cancer Colon Cancer Prostate Cancer Lung Cancer 62 years 68 years (men) 72 years (women) 67 years 72 years Dunne EF et al. JAMA. 2007;297(8): ; Centers for Disease Control and Prevention. Vaccines and Immunizations. The Pink Book: Course Textbook. 13th ed (2015). Accessed April 11, National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Accessed April 11,

3 Oropharynx Cancer 62 years 30% before age 50 years HPV related typically <50 years Anal Cancer 60 years More than 30% before age 55 years Incidence of HPV-related oral pharyngeal carcinomas are increasing Particularly among young males Cervical Cancer 47 years More than 14% before age 35 years National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Accessed April 11, 2016; Marur S et al. Lancet Oncol. 2010;11(8): ; Chaturvedi AK et al. J Clin Oncol. 2008;26(4): % of oropharyngeal carcinomas positive for HPV 16 American Cancer Society. Cancer Facts & Figures Atlanta: American Cancer Society; Accessed April 11, 2016; Chaturvedi AK et al. J Clin Oncol. 2008;26(4): ; National Cancer Institute. Annual Report to the Nation on the Status of Cancer, Accessed April 11, 2016; Marur S et al. Lancet Oncol. 2010;11(8): Pseudovirion based vaccines Based on L1 (capsid) protein Highly immunogenic Bivalent vaccine HPV 16, HPV 18 pseudovirions ASO4 adjuvant Combination of aluminum hydroxide and monophosphoryl lipid A Quadrivalent vaccine HPV 6, HPV 11, HPV 16, HPV18 pseudovirions Amorphous aluminum hydroxyphosphate sulfate adjuvant 9 valent vaccine HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 pseudovirions Amorphous aluminum hydroxyphosphate sulfate adjuvant 25 ASO4=Adjuvant System valent vaccine HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 pseudovirions Amorphous aluminum hydroxyphosphate sulfate adjuvant In females 98% for prevention of genital warts and for prevention of CIN2/3 and AIS In males 90% for prevention of external genital lesions 75% for prevention of AIN2/3 27 AIN=anal intraepithelial neoplasia; AIS=adenocarcinoma in situ; CIN=cervical intraepithelial neoplasia; PPE=parapneumonic pneumococcal empyema; qhpv=quadrivalent human papillomavirus. 28

4 Estimated type contribution for certain HPV-related cancer and disease cases 4 HPV types cause: (6, 11, 16, and 18) 9 HPV types cause a total of: (6, 11, 16, 18, 31, 33, 45, 52, and 58) Cervical cancer cases 70% 90% Vulvar cancer cases 75% 90% Vaginal cancer cases 65% 85% Anal cancer cases 85% 90% 95% High-grade cervical precancer 50% 80% Low-grade cervical lesion 25% 50% Genital warts cases 90% 90% HPV HPV de Sanjose S et al; Retrospective International Survey and HPV Time Trends Study Group. Lancet Oncol. 2010;11(11): ; de Sanjosé S et al; HPV WAP Study Group. Eur J Cancer. 2013;49(16): ; Alemany L et al; HPV WAP Study Group. Eur J Cancer. 2014;50(16): ; Alemany L et al; HPV WAP Study Group. Int J Cancer. 2015;136(1): ; Joura EA et al. Cancer Epidemiol Biomarkers Prev. 2014; 23(10): ; Garland SM et al. J Infect Dis. 2009;199(6): ; Guan P et al. Int J Cancer. 2012;131(10): HPV HPV Immunogenicity non equivalence Vaccine efficacy for disease prevention 31 Clinical study with 14,000 females (16 26 yo) received HPV4 or HPV9 HPV9 was 97% effective in preventing cervical, vulvar, and vaginal precancerous lesions by 5 additional types HPV9 as effective as HPV4 for the prevention of diseases by 4 shared HPV types by antibody response Cost benefit analysis slightly better for HPV9 than for HPV4 HPV9 costs approximately $13 more per dose, but the additional benefit from the 5 types outweighs extra cost Joura EA et al; Broad Spectrum HPV Vaccine Study. N Engl J Med. 2015;372(8): ; Petrosky E et al; Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2015;64(11): HPV4 HPV9 HPV 16/18 CIN 98.2% immunobridge HPV 16/18 VIN/VAIN 100% immunobridge Genital Warts Female 99% immunobridge Genital Warts Male 100% immunobridge AIN (male) 77.5% immunobridge Any female precancer end point from 31, 33, 45, 52, or 58 n/a 96.7% HPV4 HPV9 Injection site pain 83.5% 89.9% Swelling 28.8% 40.0% Redness 25.6% 34.0% Headache (girls only) 28.2% 14.6% Fever 5.9% 6.0% Nausea 3.7% 4.4% Dizziness 3.0% 2.8% VAIN=vaginal intraepithelial neoplasia; VIN=vulvar intraepithelial neoplasia. Gardasil [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2011; Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; Gardasil [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2011; Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co, Inc;

5 Adverse Event HPV4 Vaccine Adjuvant placebo HPV2 Vaccine Pain Swelling Erythema Temp Temp > Nausea 7 7 Malaise Adjuvant placebo IOM reviewed possible associations between adverse health events and 8 vaccines Evidence favors acceptance of a causal relationship between HPV vaccine and anaphylaxis (yeast and latex components) Evidence convincingly supports a causal relationship between the injection of a vaccine and syncope Gardasil [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2011; Cervarix [package insert]: Research Triangle Park, NC: GlaxoSmithKline Biologicals. FDA product approval data, CDC 35 Stratton K et al, eds. Institute of Medicine. Adverse Effects of Vaccines: Evidence and Causality. Washington DC: National Academies Press; Inadequate evidence was found for causal relationships between HPV vaccination and 12 other specific health events studied Syncope can occur among adolescents who receive vaccines, including HPV vaccine The ACIP recommends providers observe patients for 15 minutes after any vaccination Safety studies for HPV4 vaccine similar to safety reviews of MCV4 and Tdap vaccines More than 100 MILLION doses of HPV4 have been given The safety of HPV4 vaccine has been scrutinized more than any other vaccine because of the controversy Not just in the United States, but in many countries NO unusual safety concerns have been found Media reports are unfounded not linked to the vaccine MCV 4 =meningococcal conjugate vaccine; Tdap=tetanus, diphtheria, and acellular pertussis. Stratton K et al, eds. Institute of Medicine. Adverse Effects of Vaccines: Evidence and Causality. Washington DC: National Academies Press; Garland SM et al. Prev Med. 2011;53 suppl 1:S29-S35; Ali H et al. BMJ. 2013;346:f2032. Markowitz LE et al. J Infect Dis. 2013;208(3): ; Nsouli-Maktabi H et al. MSMR. 2013;20(2): The 9 valent HPV vaccine is recommended for routine vaccination of 11 and 12 year old males and females As with the quadrivalent vaccine, immunization may be initiated as young as age 9 years The ACIP also recommended catch up immunization with the 9 valent vaccine for females aged years and for males aged years Immunization is also recommended for males aged years if immunocompromised or MSM MSM=men who have sex with men. Centers for Disease Control and Prevention. Recommended Immunization Schedules for Persons Aged 0 Through 18 Years. Accessed April 21, For females, the ACIP does not make a preference among the 2 valent, 4 valent,or 9 valent vaccines For females, a 3 dose series with any of the vaccines is recommended For males, a 3 dose series with either the 4 valent or 9 valent vaccine is recommended Centers for Disease Control and Prevention. Recommended Immunization Schedules for Persons Aged 0 Through 18 Years. Accessed April 21, Supplemental guidance can be found at National Center for Immunization and Respiratory Diseases. Accessed April 12,

6 Safety of HPV9 was assessed in those having already received 3 doses of HPV4 921 females aged years 99% had had 3 doses within a 12 month period HPV9 provided 12 to 26 months after last HPV4 dose For the 5 new HPV types, girls who had received HPV4 previously had 25% to 63% the GMT of those who had not received HPV4 previously The clinical implications of this lower GMT is not known. These lower levels are still orders of magnitude higher than natural HPV infection % 79.3% Females 69.3% 60.0% 39.7% 41.7% Males 21.6% 57.8% GMT=geometric mean titer. Gardasil [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2011; Gardasil 9 [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; Reagan-Steiner S et al. MMWR Morb Mortal Wkly Rep. 2015;64(29): % 79.3% Females 69.2% 70.2% 47.7% Males 52.1% 62.3% 2013 Top Five Reasons for Not Vaccinating Adolescents Parents of girls Parents of boys Reason % Reason % Lack of knowledge 15.5 Not recommended % Not needed or necessary Safety concern/side effects 14.7 Not needed or necessary Lack of knowledge 15.5 Not recommended 13.0 Not sexually active 7.7 Not sexually active 11.3 Safety concern/side effects 6.9 Reagan-Steiner S et al. MMWR Morb Mortal Wkly Rep. 2015;64(29): Stokley S et al; Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC; Centers for Disease Control and Prevention (CSC). MMWR Morb Mortal Wkly Rep. 2014;63(29): Accessed April 11, BLANKET Recommendation Presumptive: We have to do some shots today Your child needs 3 shots today. HPV vaccine Meningococcal vaccine Tdap vaccine Participatory: What do you want to do about shots? Analysis of 111 vaccine conversations (50% of parents vaccine hesitant) 17.5 higher odds of resisting recommendation if permissive approach used 47% of parents let go of their initial resistance when continued presumptive recommendations were made 51 Opel DJ et al. Pediatrics. 2013;132(6):

7 Start with a presumptive, blanket approach If this is not met with acceptance, use other tools MI type conversations Fact sheets Decision aids A way of being with the client, not just a set of counseling techniques* Provider becomes a helper in the change process Works to strengthen a person s intrinsic motivation for a behavior And, most importantly, DON T GIVE UP! More about the words you use than the underlying goal MI=motivational interviewing. 53 Miller WR, Rollnick S. Motivational Interviewing: Preparing People to Change Addictive Behavior. New York, NY: The Guilford Press In response to a parent generally supportive of vaccination but with safety concerns about HPV vaccines: Instead of: Actually, studies show that there are no serious side effects from the vaccine and so I think you should let your daughter get it. It is really important. Say: It sounds like you are generally in support of vaccines, but you have concerns about the safety of HPV vaccine, is that right? Vaccination against HPV does NOT affect sexual behavior So if you had information that convinced you the HPV vaccine was safe, you might consider letting your daughter have it? Would it be OK if I shared what I know about the safety of the vaccine? 55 Jena AB et al. JAMA Intern Med. 2015;175(4): ; Bednarczyk RA et al. Pediatrics. 2012;130(5): ; Mayhew A et al. Pediatrics. 2014;133(3): ; Rysavy MB et at. J Pediatr Adolesc Gynecol. 2014;27(2): HPV Vaccine is SAFE More than 100 MILLION doses have been given. Safety studies findings for HPV vaccine similar to other vaccines 2. HPV Vaccine WORKS Vaccination can reduce HPV related cancer by 70% 3. HPV Vaccine LASTS Immunity lasts at least 9 years with no evidence of waning 4. The way you recommend the vaccine is important Strong recommendation for all the vaccines without differentiating HPV from the others Garland SM et al. Prev Med. 2011;53 suppl 1:S29-S35; Ali H et al. BMJ. 2013;346:f2032. Markowitz LE et al. J Infect Dis. 2013;208(3): ; Nsouli-Maktabi H et al. MSMR. 2013;20(2):

8 Adolescents need medical homes with providers who understand adolescent issues The vaccine works best when given at a younger age Obstetrician/Gynecologists do not care for early teens Obstetrician/Gynecologists do not see males Obstetrician/Gynecologists are poor immunizers Pediatric providers are vaccine enthusiasts Caring for teens is good business National sample of 776 US physicians (53% pediatricians, 47% family medicine physicians) Assessed physicians' perceptions and communication practices related to recommending adolescent vaccines for 11 and 12 year old patients For patients aged 11 to 12 years: 95% of physicians reported recommending for patients Tdap as highly important 87% of physicians reported recommending for patients MCV4 as highly important 73% of physicians reported recommending HPV vaccine as highly important Gilkey MB et al. Prev Med. 2015;77: Gilkey MB et al. Prev Med. 2015;77: % of physicians perceived HPV vaccine as being highly important to parents (74% for Tdap, 62% for meningococcal vaccine) Among physicians with a preferred order for discussing adolescent vaccines, 70% discussed HPV vaccine last Pertussis kills approximately 20 people per year, mostly young infants Meningococcal infections kill approximately 100 people each year By vaccinating adolescents with Tdap and MCV4 vaccines, we are working to prevent approximately 120 fatalities per year 2013 Final Pertussis Surveillance Report. National Center for Immunization and Respiratory Diseases. Accessed April 12, Gilkey MB et al. Prev Med. 2015;77: Surveillance Reports. Centers for Disease Control and Prevention. Accessed April 12,

9 Approximately 4000 women die of cervical cancer, another 1900 die of vaginal and vulvar cancer, 1000 men and women die of anal cancers, and at least 1700 die of HPV associated oropharyngeal cancers Taken together, timely HPV vaccination could prevent as many as 8000 to 10,000 HPV associated cancer deaths American Cancer Society. Cancer Facts & Figures Atlanta: American Cancer Society; Accessed April 12, When we speak doctor to doctor, we use the language of epidemiology. We talk about risk. We use statistics. Proven facts matter. The prospective, double blinded, placebocontrolled trial is the standard we demand

10 HPV stands for human papillomavirus HPV causes genital warts and cervical cancer HPVs are transmitted sexually Many adolescents become sexually active by age 13 years Do you want this vaccine for your 11 year old? Has anyone that you care about had cancer? What was it like for him or her? What was it like for you? We can reduce the chances of your son or daughter having a cancer experience Do you want to reduce your child s risk for cancer? Does it work? 2. Is it safe? 3. What is your recommendation? ) Does it work? Yes! Vaccine efficacy is high for prevention of cervical disease, genital warts, and anal malignancies. The vaccine may also protect against some head and neck cancers. 2) Is it safe? Yes! Large clinical trials and extensive postmarketing surveillance have identified sore arms and the occasional headache and fever as the only vaccine associated side effects

11 3) What is your recommendation?