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HPV-vaccines – a breakthrough in medicine Björn Strander Onkologiskt centrum Västra regionen and Kungsbacka Närsjukhus Sweden Cervical cancer ”Unusual complication to persistent infection with high risk HPV” 2 vaccines • Gardasil – MSD – Quadrivalent HPV 6,11,16,18 – Approved by European agency in september 2006 • Cervarix – GSK – Bivalent HPV 16, 18 – Approved by European agency in september 2007 VLP vaccines High antibody levels – VLPs injected i.m. give good access to lymphatics and draining lymph nodes where antibody responses are initiated and memory cells develop VLPs are very immunogenic, activating antigen presenting cells and B- and T-cells Duration of Efficacy Evaluation • The duration of efficacy of HPV-vaccines have not been determined • High efficacy of vaccines was observed through 4,5 - 5 years of follow-up • Minimum protective anti-HPV level has not been defined – No breakthroughs due to waning immunity – Antibodies remain quite stable through 4,5 - 5 years • Vaccines induces immune memory responses HPV 16/18-Related Cervical, Vulvar, Vaginal Cancer Efficacy (Via Surrogates) Per-Protocol Efficacy Population HPV 16/18Related Follow up 3 years Gardasil Placebo % Efficacy CIN 2/3 or AIS 1 42 98 86, 100 VIN 2/3 or VAIN 2/3 0 15 100 72, 100 95% CI Evidence of cross reactivity • Gardasil: 38% efficacy against CIN2+ containing 10 non-16/18 high risk HPVtypes • Cervarix: 27% protection against 12 months persistent infection with 12 non16/18 hrHPV-types Efficacy for all CIN2+ in population neg HPV 6/11/16/18 and with negativ cytologi at baseline 2.4 years follow up Expected Efficacy without cross reactivity= 99% x 0.52 = 51% Endpoint Gardasil Cases CIN2-3 or AIS 52 Placebo % Cases Efficacy 97 46 95% CI 24, 62 Conclusion Efficacy Gardasil Follow up > 2 years HPV naïve Mixed ITT population HPV 16/18related CIN2+ -99% -41% All CIN 2+ -46% -17% Conclusion Efficacy Cervarix Follow up 15 months HPV naïve HPV 16/18related CIN2+ All CIN 2+ Mixed ITT population - 90 – 100% No data No data No data Sweden • Life time risk for cervical cancer 0.7% • Can be reduced to 0.25% with screening + vaccination • NNT for preventing 1 case of cervical cancer ~ 200 • NNT for saving 1 life ~ 600 1 • Other estimates 618 - 1125 1 Brisson et al CMAJ aug 2007 Numbers needed to vaccinate to save one life • Varicellae • Meningococcus • Influenza 34 000 21 000 5 000 Vaccinating people > 65 years of age HPV and cancer Cancer % associated HPV HPV 16/18 Number in Sweden 2005 Cervix ≥95% 70% 429 Vagina 60% 55% 46 Vulva 40% 30% 128 Penis 40% 25% 80 Anus 90% 80% 130 Head and neck 20% 18% 579 Number of female cancers that could be prevented with HPV 16/18 vaccination Non-cervical in proportion of cervical cancers 489 63 % Parkin, Bray Vaccine. 2006 Aug 21;24 Socialstyrelsen Cancerstatistik www.sos.se Accessed 070315 1. 2. HPV vaccines Advantages – world wide • Breakthrough in prevention of cervical cancer • Can offer the protection for third world women with minimum side effects • Can have dramatic effect on incidence and mortality on a world scale HPV vaccines Advantages – Nordic countries • Mass vaccination of girls in school can reach those who will not attend screening • Will reduce mortality in cerival cancer • Less treatment of cancer and dysplasia will give benefits in fertility and pregnancy losses • Reduced anxiety associated with cancer and dysplasia • Reduction of other cancers are to expect • Reduction of warts (Gardasil) • Not more serious adverse events than placebo • Boys/men can benefit from herd immunity HPV vaccines Concerns • Cost • Prevent improvement of existing screening? • Need of booster vaccination? • Efficacy against cancer? – will type replacement occur? • Implementation in the third world – women hostile cultures