The Global Burden of HPV Related Cancers and Their Prevention
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1 The Global Burden of HPV Related Cancers and Their Prevention What Every Doctor Should Know! Dr. Adrian Lear, MD
2 Conflict of Interest Disclosure I have no financial relations with any commercial entity 04/05/12
3 Learning Objectives (1) Redefine human cancer and give an update on the global cancer burden. (2) Review the major known viral causes of human cancers. (3) Show how many of these dreadful cancers can be easily prevented and/or controlled by simple new technologies. (4) Encourage all of us to take ownership of these new technologies and in so doing make this a better world for mankind. 04/05/12
4 What is cancer? Cancer is not one disease but a group of >200 diseases. Cancer is the result of the loss of normal control over cell growth which interferes with: The normal mechanism of DNA repair when mutations occur, and The killing of cells(apoptosis) when repair is not possible Cancer begins with a small series of cell mutations
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7 04/05/12 World Cancer Statistics 2012
8 04/05/12 Estimated Global Age-Standardized Cancer Incidence and Mortality Rates for Males
9 04/05/12 Estimated Global Age-Standardized Cancer Incidence and Mortality Rates for Females
10 5.2%
11 Global burden of cancers attributable to infections in 2012 (The Lancet Oncology May 9, 2012) Global new cancers in 2012, 14.1 million Population attributable to infections, 18.0% or approx. 2.5 million cancer cases Viruses cause 10-15% of all human cancers worldwide HPV Infection causes 5.2% or approx. 725,000 of all cancers globally per year
12 Cancers associated with HPV
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14 The Annual Burden of HPV in Canada 04/05/12 ~510 deaths from cervical, vulvar and vaginal cancers ~1835 newly diagnosed cases of cervical, vulvar and vaginal cancers Up to 77,000 newly diagnosed cases of genital warts, VIN VAIN >325,000 abnormal Pap tests >4 million Pap tests performed 1. Akom E, Venne S. November Statistics Canada. Table CANSIM [Canadian Cancer Registry]. 3. Canadian Cancer Society / National Cancer Institute. Canadian Cancer Statistics 2005: BC Cancer Agency, Statistics Canada. Accessed at 6. Statistics Canada. Table CANSIM [Vital Statistics Death Database].
15 There Is a High HPV Disease Burden Globally? Estimated annual new HPV-related disease cases in both sexes Male Female Penile cancer Vulvar & vaginal cancer 10,500 19,960 Anal canal Anal canal 13,000 14,300 Head and neck cancer Head and neck cancer 42,000 18,000 Cervical cancer 529,600 Total Cancers Total Cancers 65, ,860 Genital warts Genital warts 17,600,000 14,400, WHO/ICO Information centre on HPV and cervical cancer. Summary report 2010.
16 Sites With Increased Susceptibility to Mucosal HPV Sites Ectocervix Anal Canal Labia majora, Labia minora Vagina Glands penis (uncircmucised), Foreskin, Urethra Tongue (dorsal), Hard palate, Oral cavity, Tonsil (crypt), Vocal folds Cornea / Conjunctiva Esophagus (Proximal) Subungual
17 Episomal HPV
18 A: Episomal HPV16 DNA B: Integrated HPV16 DNA
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25 HPV Vaccines
26 Public Health Achievements in 20th Century Vaccination Immunization has saved more lives globally in the last 50 years than any other health intervention! Hygiene and clean water Motor-vehicle safety Safe workplaces Control of Infectious Diseases Decline in deaths due to coronary heart disease and stroke 04/05/12
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31 Monovalent Vaccine HPV-16 VLP First commercial HPV VLP experimental vaccine used in California and Costa Rica. Vaccine replaced by Gardasil in 2006 due to single HPV high risk genotype.
32 Bivalent Vaccine HPV-16 VLP HPV-18 VLP Vaccine produced by GSK and covers mainly two high risk HPV genotypes. The vaccine also has limited cross protection with three more high risk genotypes. Does not cover venerial warts. 04/05/12
33 HPV 18 EU/ml HPV 16 EU/ml High and Sustained anti-hpv 16/18 Immune Response To GSK Bivalent Cervarix Vaccine 10,000 Seropositivity 98% at all time points 1 1, Antibody level 13-fold higher than natural infection level , Seropositivity 98% at all time points , Antibody level 11-fold higher than natural infection level Months *By ELISA Adapted from De Carvalho, N et al. Vaccine 2010;28:
34 Merck Quadrivalent Gardasil Vaccine HPV-16 VLP HPV-18 VLP HPV-6 VLP HPV-11 VLP Includes the same two high risk HPV genotypes as the bivalent vaccine but covers external genital warts as well. It will be replaced in 2015 by a 9-valent vaccine. 04/05/12
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36 Serum clia GMT (mmu/ml) (log 10 scale) Serum clia GMT (mmu/ml) (log 10 scale) Gardasil : antibody levels up to 5 years for HPV 16/18 * Antibody levels reported here are measured by different methods and in separate studies for Cervarix TM and Gardasil and therefore absolute levels cannot be directly compared Gardasil Phase II study up to 5 years 10,000 1,000 Gardasil Natural infection HPV * * * vaccination Antibody level several-fold higher than natural infection 10,000 HPV 18 1, Gardasil Natural infection Seropositivity decreased to 65% at 5 years 10 * * * vaccination Months 30 Antibody level similar to natural infection levels Adapted from Olsson SE, et al. Vaccine 2007; 25: ; Villa LL, et al. Vaccine 2006; 24:
37 Comparison of Cervarix and Gardsil in Preventing CIN2+, CIN3 and CIN3+ Vaccine Efficacy CIN2+ associated with CervarixTM 1,2 (women age yrs) Gardasil 3-5 (women age yrs) HPV-16/18* 98% (96.1% CI ) 98% (95% CI ) HPV-31 89% (95% CI 66-98) 70% (95% CI 32-88) HPV % (95% CI ) 52% (95% CI ) Any HPV type 65% (96.1% CI 53-74) 43% (95% CI 24-57) CIN3 associated with any HPV type 43% (95% CI 13-63) CIN3+ associated with any HPV type 93.2% (95% CI 79-99)
38 Percentage Decrease in Genital Warts Post Gardasil Vaccination in Women and Men <21 years, and MSM all ages, July 2004 to end June Vaccination program commences < 21 Female < 21 Male MSM Proportion of patients aged < 21 years, diagnosed as having genital warts by risk group compared with MSM of all ages: Read TRH, Hocking JS, Chen MY, et al. Sex Transm Infect MSM, men who have sex with men, men < 21 years excluded MSM, and non residents excluded. 04/05/12 6 Month period since July 2004
39 HPV genotype HPV types in cervical cancer worldwide Cumulative percentage Percentage of cervical cancer cases attributed to the genotype 04/05/12 Muňoz N et al. Int J Cancer 2004;111:
40 Gardasil Cross-Protective Immunity Against CIN 2/3 or AIS in HPV-Naïve Population CIN 2/3 or AIS* No. of cases Gardasil vaccine No. of cases placebo Efficacy 95% CI HPV 31/ % 10, 85 HPV 31/33/45/52/ % 7, 66 HPV 31/33/35/39/45/51/ 04/05/12 52/56/58/ % 6, 60
41 New Next Generation 9-Valent Vaccine Viral like particles HPV 16 HPV 18 HPV 6 HPV 11 HPV 31 HPV 33 HPV 45 HPV 52 HPV 58 This vaccine will cover approximately 98% of the HPV genotypes in cervical cancer worldwide. This vaccine have been extensively tested in Denmark and has proven to be safe and efficacious with minimal side effects. This vaccine will replace the present quadrivalent (Gardasil) vaccine. 04/05/12
42 Next Generation 9-valent HPV Vaccine Potential impact against disease and cancer caused by these 9 HPV types What is the disease attribution of these 9 HPV types? 04/05/12
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47 Vaccine Uptake in Public Programmes UK- 80 to 88% coverage US 35 42% coverage 3 doses 15-21% in US in 2008 Regional variation: Texas 21%, New York 50% Canada: Ontario, Alberta 50% NL >90% HPV vaccines are approved and used in 150 countries throughout the world 04/05/12
48 Dr. Xavier Bosche The research on HPV has been done. The time has come for society to embrace the new technologies. -HPV meeting, Seattle August 2014
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