Summary 1. 2 Dose Schedule 2. 9HPV vaccine 3. Primary HPV screening 4. Male vaccination 5. Update on Australia 6. Natural History 7. OPC and Anal
2 dose schedules The train has left the station
2 dose data Data comes from Randomized trials of 2 vs 3 Ad hoc analysis within existing trials Effectiveness studies
2 dose data Girls 9-13 0,6 months Good immunogenicity and safety profile for 4 years of followup Duration of protection not known Dobson, etal. A randomized controlled trial to assess immunogenicity of a two dose quadrivalent human papillomavirus vaccine schedule in Canadian younger adolescents: results to Month 36. Journal of the American Medical Association 2013. 309(17):1793-1802 Romanowski et al. Immune response to the HPV 16/18 AS04-adjuvanted vaccine as a 2 dose or 3 dose schedule up to 4 years after vaccine. Human Vaccines and immunotherapeutics 2014: 10(5);1155-1165
Safaeian et al Costa Rica Vaccine trial oral obstract HPV conference 2014
WHO GAVI has changed its alliance to 2 dose only 20 African countries now have to switch
Countries 2 Dose Canada UK France Netherlands Austria Italy Spain Switzerland South Africa Columbia Mexico Brazil
2 Dose questions Recommended schedule is 0,6 New Zealand 0,2,6 stop after the 0,2? 0, 12? No data for males but should be OK What happens when the 9HPV vaccine gets approved?
Other schedules
1 dose Small studies show 1 dose results in immune response 10X better than natural infection, lower than 2-3 dose, maintained to 4 years
Extended schedules Can the current 0, 2, 6 be extended to 0,6,12 0,12,24
9HPV
9HPV No name Cost not known Has now completed trials and under review by FDA Expected to be available 2015 in a 3 dose schedule Includes 5 HPV types 31/33/45/52/58
Non Inferior Trials done on girls 15-26 randomized to 4 v 9HPV 3 dose schedule Same adjuvant as 4HPV High efficacy end points 97% Bridging immunogenicity trials in younger girls and boys 9-15 Good safety profile
90% protection CIN
Discussion How to implement (policy issues) Cost 9HPV in 2 dose schedules What will happen to availability of 4HPV I m halfway through my gardasil, can I switch over? I ve completed my gardasil, can I have the 9HPV?
Sept 1 2014
??? 4HPV 3 dose 4 HPV 2 dose 9 HPV 3 dose 9 HPV 2 dose
What Should We Do? Continue current program with Gardasil Switch to 9HPV 2 dose schedule Gender Neutral
HPV Primary Screening
Countries where starting Australia (pending final approval) Primary HrHPV screening 16/18 genotyping Start age 25 to 70-74 Interval 5 years
Countries where starting The Netherlands Starting 2016 Italy Already started based on large NTCC trial USA FDA has approved 16/18 primary screening with reflex cytology Start age 25 Awaiting guidelines from ASCCP
The Invisible Man
Male Vaccination Herd immunity is not realistic MSM are not covered by a girl only program Modeling in Australia shows you get better HPV control in a gender neutral program* Cost is not a barrier *megan smith et al vaccine 2011
Vaccination female and male
Australia- update on male vaccination
General Update HPV vaccination induces very good immune memory response. The current bivalent and quadrivalent vaccines are at 8-10 years of followup safety profile remains excellent and there is no evidence of waning protection. To date (2014) there are 54 countries which are providing HPV vaccination
Population impact data Only some countries able to provide surveillance data Decreasing rates of HPV prevalence 4 countries external genital warts 6 countries cervical lesions 2 countries
Update New Zealand 31 July 2014
The latest fully vaccinated cohort is born 2000 : Dose 1 = 62% Dose 2 = 60% Dose 3 = 56%
GENITAL WARTS Five years of HPV4 and how low can we go? Dr Jeannie Oliphant
Update Australian Data
Monitoring outcomes 1. Two DNA prevalence studies 2. CIN disease 3. External genital warts 4. RRP 5. Cancers
Natural History Some things to think about
We all agree Natural infection does not always result in seroconversion or in an immune response that is protective 70-80% of women and only 30-40% of men sero convert
Is finding HPV DNA a definition of infection?
Do we really understand clearance, latency or reactivation?
Persistence vs Shedding or Blipping
A negative HPV test reflects undetectable virus
Risk of high grade disease is likely to be related to detectable virus that is persistent and also in high copy number Just being positive over two points in time may not represent a true increase in risk of disease
Oral and Anal
Anal Cancer Cervical cancer currently 1-2/100,000 Cervical cancer before screening ~40/100,000 Anal cancer HIV negative men and women 1.5 HIV negative MSM 37 HIV positive MSW 47 HIV positive Women 30 HIV positive MSM 131 Silverberg M et al CID 2012; 54:1026-34