Summary Dose Schedule 2. 9HPV vaccine 3. Primary HPV screening 4. Male vaccination 5. Update on Australia 6. Natural History 7.

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2 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

3 2 dose schedules The train has left the station

4 2 dose data Data comes from Randomized trials of 2 vs 3 Ad hoc analysis within existing trials Effectiveness studies

5 2 dose data Girls ,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 (17): 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);

6 Safaeian et al Costa Rica Vaccine trial oral obstract HPV conference 2014

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8 WHO GAVI has changed its alliance to 2 dose only 20 African countries now have to switch

9 Countries 2 Dose Canada UK France Netherlands Austria Italy Spain Switzerland South Africa Columbia Mexico Brazil

10 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?

11 Other schedules

12 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

13 Extended schedules Can the current 0, 2, 6 be extended to 0,6,12 0,12,24

14 9HPV

15 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

16 Non Inferior Trials done on girls 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

17 90% protection CIN

18 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?

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20 ??? 4HPV 3 dose 4 HPV 2 dose 9 HPV 3 dose 9 HPV 2 dose

21 What Should We Do? Continue current program with Gardasil Switch to 9HPV 2 dose schedule Gender Neutral

22 HPV Primary Screening

23 Countries where starting Australia (pending final approval) Primary HrHPV screening 16/18 genotyping Start age 25 to Interval 5 years

24 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

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26 The Invisible Man

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28 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

29 Vaccination female and male

30 Australia- update on male vaccination

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34 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

35 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

36 Update New Zealand 31 July 2014

37 The latest fully vaccinated cohort is born 2000 : Dose 1 = 62% Dose 2 = 60% Dose 3 = 56%

38 GENITAL WARTS Five years of HPV4 and how low can we go? Dr Jeannie Oliphant

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41 Update Australian Data

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45 Monitoring outcomes 1. Two DNA prevalence studies 2. CIN disease 3. External genital warts 4. RRP 5. Cancers

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47 Natural History Some things to think about

48 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

49 Is finding HPV DNA a definition of infection?

50 Do we really understand clearance, latency or reactivation?

51 Persistence vs Shedding or Blipping

52 A negative HPV test reflects undetectable virus

53 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

54 Oral and Anal

55 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:

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