Deploying HPV : lessons from Australia

Ian Frazer, Research Director, The Translational Research Institute Brisbane, Australia is 100% due to HPV infection, and kills 250,000 women per year, mostly in the developing world

ALL CANCERS CERVICAL CANCER Controlling HPV infection is a challenge

Preventing the infection seems more sensible HPV vaccine development: A 15 year $1 billion process

Zur Hausen

Jian Zhou

Cancer associated Virus Like HPV Human particles1 (~2005) Papillomaviruses (~1990)

(~1980)

1:J. Zhou, X. Y. Sun, D. J. Stenzel, and I. H. Frazer. Virology 185 (1):251-257, 1991. -needing many people and a hard end point to prove efficacy

Vaccine Study1 Vaccine2 No of subjects End-points efficacy1

Vaccine Control % ( confidence limits) Koutsky 6/11/16/18 6087 6080 CIN 2/3 AIS 98 (86-100) Ault 6/11/16/18 10291 10292 CIN 2/3 AIS 99 (93-100) 2241 2258 CIN 2/3 AIS 100 (94-100) 6/11/16/18 Garland 2261 2279 GW VIN VAIN 100 (94-100) 7811 7785 VIN2/3 VAIN 100 (72-100) 6/11/16/18 Joura 2/3 CIN2,3 93 (89-98) Parvonen* 16/18 9319 9325

1: prevention of premalignancy in HPV Adapted from J. A. Kahn and R. D. Burk. Papillomavirus vaccines in naïve subjects, for prevention of disease perspective. Lancet 369 (9580): caused by vaccine HPV types 2135-2137, 2007.

*: Phase III bivalent vaccine data from 25th IPV Malmo 2009 Nine steps to prevention of HPV associated cancer • Define the problem – HPV and cancer Zur Hausen • Develop the science –recombinant VLPS Jian Zhou • Find commercial partners Merck/GSK • Scale up the manufacture Merck/GSK • Complete safety and efficacy trials Many groups • Educate the profession, govt, the public Ongoing • Confirm field efficacy • Improve the product – 9 valent vaccines, 2 dose regimens • Encourage deployment globally • Develop effective immunotherapy Population-based coverage estimates for HPV vaccine in Australia by age in mid 2007, as at March 2011

Measuring human papillomavirus (HPV) vaccination coverage and the role of the National HPV Vaccination Program Register, Australia, Dorota M. Gertig A, Julia M. L. Brotherton A B and Marion Saville A Sexual Health 8(5705) 171– 178 http://dx.doi.org/10.1071/SH10001 Three dose HPV vaccination coverage in Australian women aged 18–26 years in 2007 estimated by three methods

Julia M.L. Brotherton , Bette Liu , Basil Donovan , John M. Kaldor , Marion Saville Vaccine, Volume 32, Issue 5, 2014, 592 – 597 http://dx.doi.org/10.1016/j.vaccine.2013.11.075

Uptake of HPV vaccines across Australia (3 doses, 15 y.o’s) Since the introduction of vaccination in Australia, HPV related disease has virtually disappeared in vaccinated young women

Ali, H. Et al BMJ 2013;346:f2032 doi: 10.1136/bmj.f2032 ..and in unvaccinated young men!

Ali, H. Et al BMJ 2013;346:f2032 doi: 10.1136/bmj.f2032 Differences in HPV genoprevalence between prevaccine and postvaccine populations.

Tabrizi S N et al. J Infect Dis. 2012;infdis.jis590 Reduction in HPV related cervical disease by age at immunisation

Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study. Dorota M Gertig, , Julia ML Brotherton, Alison C Budd, Kelly Drennan Genevieve Chappell and A Marion Saville BMC Medicine 2013, 11:227 doi:10.1186/1741-7015-11-227