HPV Vaccination: A Missed Opportunity for Cancer Prevention Kevin A. Ault, MD Tuesday, July 26, 2016 New Developments in 2015-16 a second generation polyvalent HPV became available for use in 2015 HPV vaccine uptake remains low especially in Kansas More available data on increasing vaccine uptake based on office practices 2 Objectives for today s talk 1. discuss the variety of cancers caused by HPV infection 2. strongly recommend HPV vaccination in an office setting 3 1
Infections and Cancers: Global Burden Infection Cancer # cases worldwide % worldwide H. pylori stomach 490,000 5.4 HPV Cervix etc 550,000 6.1 Viral Liver 390,000 4.3 hepatitis Totals 1.6 million 17.7 Source World Health Organization 4 The Transformation Zone Is Most Vulnerable to HPV-related Disease The squamo-columnar junction marks the transition from a stratified squamous to a glandular epithelium Cutaneous HPVs Epidermodysplasia verruciformis HPV Mucosal/Genital HPVs (low-risk) Mucosal/Genital HPVs (high-risk) Slide courtesy of Dr. William Bonnez, University of Rochester 5 6 2
HPV Associated Cervical Cancer Incidence Rates by State, United States, 2006 2010 www.cdc.gov/cancer/npcr Cervical Cancer Rates 2004-2008 USA, by Race/ethnicity Source: CDC 2012 8 Burden of Disease HPV and the Cervix In developed world, most costs associated with detection and treatment of pre - malignant disease Long duration between initial exposure and development of cervical dysplasia or cancer Cost in USA - $ 6.6 Billion Likely same pathogenesis for cervical, anal and ENT cancers Chesson et al 2012 9 3
Prevalence of HPV related cancers Cervical cancer rates have decreased 80% However anal cancer and HPV related ENT cancers are increasing Chaturvedi et al 2011 10 HPV related ENT Cancer Males by state, USA 2006-2010 11 HPV Vaccine Ten years of data 2015 update on clinical recommendations Efficacy Safety Uptake 12 4
Summary of current ACIP recommendations 2015 routine vaccination of adolescent females and males aged 11 12 years with 3 doses of HPV vaccine. The vaccination series can be started as young as age 9 years. Catch up to age 26 Three versions of the HPV vaccine currently available, second generation is 9 valent See http://www.cdc.gov/vaccines/pubs/acip-list.htm#hpv or MMWR 13 External Genital Warts - Diagnosis by Age Australia Source: Ali et al 2013 14 HPV Types that Cause Cervical Cancer- Global Survey De San Jose et al 2010 15 5
Potential Impact of HPV9 Vaccine USA 2015 by cancer site Saraiya et al 2015 From the website Spurious Correlations 17 HPV Vaccine Safety The most common adverse events reported were considered mild For serious adverse events reported, no unusual pattern that would suggest that the problems were related to the HPV vaccine 75 million doses of HPV vaccine distributed in US since 2006; almost all quadrivalent vaccine Slade et al 2009 6
Recent Safety Monitoring Publications: Autoimmune Diseases No increased risk of autoimmune disorders 16 autoimmune conditions at two health plans among 189, 629 vaccinated females (US) 23 autoimmune, 5 neurologic conditions and VTE* among 296,826 vaccinated females (Denmark and Sweden) 6 autoimmune outcomes among 1,365 (269 cases, 1,096 controls) (France) *Venous thromboembolism Chao et al 2012, Arnheim-Dahlstrom et al 2013, Grimaldi-Bensouda et al 2013 Recent Safety Monitoring Publications: Pregnancy and Neurological Diseases No known risks with inadvertent administration during pregnancy No increased risk of neurological diseases Multiple sclerosis and demyelinating diseases among 789,082 vaccinated (Denmark) Dechamps et al 2009 Moro et al 2015 Scheller et al 2015 Recent Concerns in HPV Vaccine Safety Primary Ovarian Insufficiency (POI) Case reports in the media led to public concern No safety findings in VAERS 1 Complex Regional Pain Syndrome (CRPS) Case reports in Japan of pain following HPV vaccination led to suspension of their HPV vaccine recommendation Review and adjudication of case reports found no evidence for causal association observed between 2vHPV and CRPS 2 No safety findings in VAERS Postural Orthostatic Tachycardia Syndrome (POTS) Concerns in Europe led to European Medicines Agency (EMA) review of POTS (and CRPS) following vaccination 3 Review did not find evidence to support that HPV vaccine caused POTS or CRPS 1 http://www.cdc.gov/vaccinesafety/vaccines/hpv/hpv-safety-faqs.html; 2 Huygen et al. Investigating Reports of Complex Regional Pain Syndrome: An Analysis of HPV-16/18-Adjuvanted Vaccine Post-Licensure Data. EBioMedicine. 2015.; 3 http://www.ema.europa.eu/docs/en_gb/document_library/press_release/2015/07/wc50018 9481.pdf 7
Estimated HPV Vaccination Coverage among Adolescents Aged 13-17 Years in United States, 2006-2014 1 Tdap 1 MenACWY 1 HPV (F) 1 HPV (M) 3 HPV (F) 3 HPV (M) MMWR 64(29);784-792 * APD = Adequate provider data Data from CDC slide courtesy of Dr. Melinda Wharton 23 Top 5 Reasons Not to Vaccinate Not needed, unnecessary Not sexually active Safety Concerns Lack of disease specific knowledge No provider recommendation Source: CDC/ACIP Meeting June 2013 24 8
Missed Opportunities HPV Vaccination 84 % of unvaccinated adolescent girls had a visit where another vaccine was given Best practice electronic prompts, centralized databases, scheduled follow up, catch up in young adults If 80 % of current adolescents were vaccinated then 53,000 cases of cervical cancer would be prevented MMWR July 2013 25 Major Weaknesses of Provider Recommendations Risk based strategies Lack of urgency (delayed to future visit) Weaker recommendation for males Correlation of high quality recommendation a) child is due for adolescent vaccines b) strong recommendation c) prevents multiple cancers and d) elicit questions Gilkey et al 2015 26 Why Is HPV Vaccine Coverage So Low? Parents Parents are not offered vaccination Parents perceive vaccine as optional or unnecessary at that time Parents perceive that their providers discouraged vaccination Parents want information about vaccine safety Parents do not understand the reason to vaccinate at 11 to 12 years of age Providers Providers are reluctant to give multiple shots at one visit Providers introduce HPV vaccination at age 11 years but do not recommend it strongly Providers recommend vaccination based on their estimation of sexual activity Providers have limited experience with HPV and underestimate risk Providers perceive HPV as more emotionally charged than other vaccines Delaying vaccination leads to nonvaccination Perkins RB et al. Pediatrics 2014;134:e666-e674 9
Conclusions Many HPV related cancers on the rise HPV vaccines are safe, effective and underutilized Newest version of the HPV vaccine could prevent 90 % of cervical cancers Provider recommendation best predictor of HPV vaccine uptake 29 Thank you ever so much Any questions? Kevin A. Ault, MD Department of Obstetrics and Gynecology 3901 Rainbow Blvd University of Kansas Medical Center Kansas City KS USA 66160 kault2@kumc.edu or Twitter @kevinault 30 10