Planning an effective HPV vaccination launch: The key indicators for success Joakim Dillner

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1 Planning an effective HPV vaccination launch: The key indicators for success Joakim Dillner Professor of Infectious Disease Epidemiology PI, International HPV Reference Center Director, Swedish Cervical Cancer Prevention Registry Director, Swedish National Biobanking Infrastructure (BBMRI.se) PI, Nordic Center of Excellence in Health-related esciences Karolinska Institute and Karolinska Hospital, Stockholm, Sweden Joakim Dillner 21/04/2015 1

2 Basic facts firmly established and communicated. Vaccine characteristics: *Near-complete efficacy against HPV infection but only if not previously infected. *High burden of diseases caused by HPV (not only cervical cancer) *Large experience: >100 million vaccinations performed already *Long-lasting protection *Vaccine prices are dropping rapidly (now 20% or less of original levels) no longer an expensive vaccine. Joakim Dillner 21/04/2015 2

3 Vaccination strategies need to be organised Organised school-based programmes Better uptake and compliance vs. on-demand vaccination Country Age Years) School-based Coverage (%) England¹ Yes 80% Australia² Yes 73% Greece³ No 15% US¹ No 32% Sweden Before % Sweden Start % 1. dh.gov & cdc.gov 2. health.gov.au 3. SPMSD Greece internal data 4. Sweden HPV Vaccination Registry

4 HPV vaccination in Sweden : No organised vaccination. Vaccine available and subsidized for girls yrs of age. Un-organiserad vaccination: Only 29,7% coverage. About 15 times (!) more common to vaccinate if the parents have university education (Leval et al, 2013). Organised vaccination 2012: yrs of age in schools; yrs organised (in schools or primary care centers, but always with population-based appointments). HPV-vaccination registry in effect since 2006 (Research project). Mandatory government registry since 1/

5 Linkage of the HPV Vaccination Registry and the National Education Registry: Opportunistic vaccination reaches mainly girls whose parents have university education (Leval et al, JNCI, 2013) Vaccination of girls <20 years of age RRR, (95%CI) Vaccination of girls 20 years of age or older P-value ** Education of Mother Not registered 0.15 (0.13 to 0.17) 0.52 (0.39 to 0.69) <.01 <High School Reference Reference High School 4.79 (4.64 to 4.94) 2.88 (2.52 to 3.30) <.01 University 8.58 (8.32 to 8.85) 9.49 (8.34 to 10.80) 0.14 Education of Father Not registered 0.18 (0.17 to 0.20) 0.50 (0.41 to 0.60) <.01 <High School Reference Reference High School 2.75 (2.69 to 2.81) 1.70 (1.54 to 1.88) <.01 University 4.31 (4.22 to 4.41) 5.40 (4.91 to 5.94) <.01 Education of Parents Not registered 0.19 (0.16 to 0.23) 0.80 (0.56 to 1.14) <.01 <High School Reference Reference High School 7.48 (7.09 to 7.90) 3.15 (2.57 to 3.87) <.01 University (14.65 to (10.37 to 15.47) 0.06

6 Update on Swedish vaccination program Vaccination coverage school vaccinations June 2013 by county (women born ) Percent County

7 100 Vaccination coverage catch-up vaccinations June 2013 by county (women born ) Percent County

8 WHO global recommendation on HPV vaccination: Organized, school-based vaccination globally recommended. Monitoring of coverage and safety. Effectiveness monitoring performed to a different extent in different countries. -Global WHO HPV LabNet defined international QC criteria for HPV assays intended for effectiveness monitoring. But what is actually being done in the different countries of Europe?

9 Survey on organization and quality control sent to all EU/EFTA countries Reported organization status Organized vaccination: 16 countries Only females (ages 10-14) targeted Catch-up program in 9 countries Opportunistic vaccination: 11 countries Defined as: program under development, vaccination purely opportunistic, vaccination included in immunization schedule but no governmental sponsorship Namn Efternamn 21 april

10 EU Vaccination program survey Organization and quality assurance of HPV vaccination programs in Europe (Vaccine 2015) Table 3. Vaccination monitoring and evaluation efforts, among countries reporting an organized vaccination program a Country Centralized immunization Vaccine safety Registry linkages Indicators used for evaluating the impact of HPV vaccination register system b possible Denmark Yes Yes Yes Prevalence of abnormal pap smears; incidence of other HPV-related disease; CxCa mortality & mortality from other HPV-related cancers; frequency of surgical intervention; Association between vaccine uptake and cervical screening England No Yes -- HPV prevalence, HPV immunity in the population; prev. of abnormal pap smears; screening participation by vaccination status; HPV typing of lesions & cancers; CxCa incidence; incidence of other HPV related diseases & cancers; CxCa mortality & mortality from other HPV-related cancers Ireland Yes Yes No -- Italy Yes Yes -- Prev. of abnormal pap smears; CxCa incidence; CxCa mortality & mortality from other HPV-related cancers. Latvia No Yes No Policy not fully defined, but HPV prevalence & CxCa incidence have been considered. Malta Yes Yes Netherlands Yes Yes Yes -- Norway Yes Yes Yes HPV prevalence; prevalence of abnormal pap smears; screening participation by vaccination status; HPV typing of precancerous lesions & CxCa; CxCa incidence; incidence & typing of other HPV-related cancers; CxCa mortality & mortality from other HPV-related cancers; frequency of surgical interventions. Scotland Yes Yes Yes HPV prevalence; prevalence of abnormal pap smears; screening participation by vaccination status; rates of CIN by immunization status. Slovenia Yes Yes No HPV prevalence; screening participation by vaccination status; HPV typing of precancerous lesions & CxCa; CxCa incidence; incidence & typing of other HPV-related cancers; incidence of other HPV-related disease; CxCa mortality & mortality from other HPV-related cancers. Spain Yes Yes Sweden Yes Yes Yes HPV prevalence, HPV immunity; screening participation by vaccination status; HPV typing of precancerous lesions, CxCa; incidence & typing of other HPV-related cancers; incidence of other HPV-related disease; CxCa incidence & mortality; mortality from other HPV-related cancers; frequency of surgical intervention. Switzerland No c Yes No Prevalence of abnormal pap smears; screening participation by vaccination status; HPV typing of precancerous lesions & CxCa; HPV typing of CxCa & CxCa mortality. Wales Yes Yes Yes HPV prevalence; screening participation by vaccination status; CxCa incidence. Elfström 21 april

11 Organization and quality assurance of HPV vaccination programs in Europe Table 1. Organized vaccination program details, among EU/EFTA countries reporting information on vaccination implementation Vaccination Age range of target Organized program start Catch-up Target population of catchup program program between Vaccine used in the differences Country population date program offered (females) districts Belgium Flemish: 2010 French: 2011 Rec d: Reim: and Denmark 2008/10 12 Yes England 2008/9 Ireland Italy 2010/5 (pilot) (routine) 2007/7-2008/11 (by region) (routine), available up to 18 Yes in 2008, free to women up to 27 Females born 1990/9/1-1995/8/31 1st 1990 Flemish: Quadrivalent French: Bivalent Opportunistic: Both Yes Vaccination delivery strategy School-based Quadrivalent No Physician admin. Bivalent: 2008/9-2012/8 Quadrivalent: 2012/9 12 Yes 18 year olds Quadrivalent No School-based 11 Yes, only some regions 14-45, by region. Males up to 26 in 1 region Bivalent & quadrivalent (by region) No Yes School-based, some physician admin. Delivered at public local health unit vaccination services Latvia 2010/9 12 No Bivalent No School-based/physician admin Luxembourg 2008/3 12 No Malta Fall (born 2000) No Bivalent No Invited to appt at the immunization center in the local health center Netherlands Yes year olds Bivalent No Mass-vaccination through the Public Health Services. Norway 2009/8 12 No Quadrivalent No School-based Scotland 2008/ Yes year olds Bivalent: Quadrivalent: 2011 No School-based Slovenia 2009/9 12 No Quadrivalent No School-based Spain 2008, varies by region 9-14 No Bivalent & quadrivalent School-based/clinic by region Sweden Yes year olds born after 1993 Quadrivalent No School-based Switzerland 2008/ Yes 15-19, free for year olds Bivalent & quadrivalent Yes School-based/physician admin Wales 2008/9 12 Yes Up to 19 year olds Bivalent: 2008/9-2012/8 Quadrivalent: 2012/9 No School-based Elfström 21 april

12 Distribution of vaccination delivery strategies among countries reporting an organized vaccination program. 21 april

13 HPV vaccination program registry and safety system status All but three countries reported having a centralized immunization register All countries reported having a vaccine safety system in place for reporting adverse events following vaccination 6 countries could perform data registry linkages Namn Efternamn 21 april

14 HPV vaccination program - monitoring Most common indicators used to monitor vaccination impact in population HPV-related disease incidence and mortality (most countries) Screening attendance by vaccinated women (England, Norway, Scotland, Slovenia, Sweden, Switzerland, and Wales) Prevalence of HPV in the population (England, Norway, Scotland, Slovenia, Sweden, and Wales) Prevalence of abnormal screening results (Denmark, England, Italy, Norway, Scotland, Sweden, and Switzerland) HPV-typing of precancerous lesions (England, Norway, Slovenia, Sweden, and Switzerland). Namn Efternamn 21 april

15 HPV vaccination program - monitoring Screening attendance by vaccinated women (England, Norway, Scotland, Slovenia, Sweden, Switzerland, and Wales) Sweden (Herweijer et al, submitted): Registry linkage between the HPV vaccination registry and the national cervical screening registry (all women in Sweden). Screening attendance was 86% in vaccinated women and 75% in unvaccinated women. T Crude HR 1.31 (95% CI ) Adjustment for education and income: (HR adj =1.09, 95% CI ). Second screening round (3 years later): Similar results: (crude HR=1.26, 95% CI ; HR adj =1.15, 95% CI ). Namn Efternamn 21 april

16 Decrease of HPV in the population Samples from Chlamydia screening in Southern Sweden were HPV-tested samples from 2008, 5224 in 2012, and 5815 in 2013 Significant decrease in vaccine-types in women ages HPV type % reduction 6 7.0% 4.2% -40.0% % 8.7% -41.6% % 4.3% -45.6% Marginal decrease in type 18 among women ages and no decrease in older women for types 16 and 6 (only small changes in vaccination coverage) No other types decrease. Increase in types 52 and 56 Soderlund-Strand A, Uhnoo I, Dillner J. Change in Population Prevalences of Human Papillomavirus after Initiation of Vaccination: The High-Throughput HPV Monitoring Study. Cancer Epidemiol Biomarkers Prev Elfström April 21,

17 Highly significant decline seen for major vaccine types post-vaccination (HPV16: -42% in vaccinated birth cohorts) n=9644 in 2008, n=1433 in 2012 and n=1383 in Joakim Dillner 21/04/

18 Australia: School vaccination yrs (80% attendance; start april 2007); organised in primary care yrs (54% attendance; start July 2007). 4 years later condylomas are disappearing (except among >30 yrs old and MSM). HPV infections are disappearing (Tabrizi et al, Lancet ID 2014).

19 HPV vaccination program - conclusions Organized vaccination programs work. Most robust if delivered at schools. Dis-organized vaccination programs have lower coverage and strong inequity. Effectiveness not routinely reported, but reported results so far are quite promising. With greater standardization of indicators, more valid comparisons between programs would be possible. Attention should be given to mapping emerging vaccination strategies so that effectiveness and success of these efforts can be compared and adjusted. Further changes are likely and should be captured through repeating international questionnaires at regular intervals. Namn Efternamn 21 april