Embed Size (px)
Citation preview
Synspunkter fra kliniker med nSynspunkter fra kliniker med næær r 10 10 åårs erfaring med rs erfaring med HPVHPV--vaksinasjonvaksinasjon og og --forskning forskning
O.E.IversenO.E.IversenInstitutt for Klinisk Medisin, UiB ogInstitutt for Klinisk Medisin, UiB og
Kvinneklinikken,Kvinneklinikken,Haukeland UniversitetssykehusHaukeland Universitetssykehus
Oslo 1.4.09Oslo 1.4.09
Tillitsverv/oppdrag Tillitsverv/oppdrag O.E.IversenO.E.Iversen
l 1992-2004. Styremedlem, Kreftforeningen
l 1997-99. Leder Norsk Forum for GynekologiskOnkologi.
l 2000-2005. Nestleder Norsk GynekologiskForening (NGF)
l 2001-forts. Medlem i Rådgivingsgruppen for Masseundersøkelsen mot livmorhalskreft (NGF).
l 2000-forts. Rgional og nasjonal koordinator for HPV vaksinestudier. (Merck/MSD og GSK)
l (2005-6) Medlem i FHI arbeidsgruppe om HPV vaksinasjon
l NB: Ikke Gynkreftforeningen!!
The Nobel Prize in Physiology or Medicine2008 Harald zur Haussen
"for his discovery of human papillomaviruses causing cervical cancer"
The Nobel Prize in Physiology or Medicine2008 Harald zur Haussen
"for his discovery of human papillomaviruses causing cervical cancer"
October 6th 2008
Milepeler i utvikling av HPV vaksiner Milepeler i utvikling av HPV vaksiner
Basic research 1974 Evidence 1983
Production of VLP s 1995-
Authorities engagement 1995-
Pharmaceutical industry 1995-
Clinical research 2000- (Phase I-III)
Volounteres 2000-
First vaccine publication NEJM 2002
Authorization of vaccine 2006
National vaccine programs 2006-
Long term follow-up (Nordic) 2006 -
Nobel Prize H zur Haussen 6. oct 2008
Basic research 1974 Evidence 1983
Production of VLP s 1995-
Authorities engagement 1995-
Pharmaceutical industry 1995-
Clinical research 2000- (Phase I-III)
Volounteres 2000-
First vaccine publication NEJM 2002
Authorization of vaccine 2006
National vaccine programs 2006-
Long term follow-up (Nordic) 2006 -
Nobel Prize H zur Haussen 6. oct 2008
Rates of Diagnoses of Genital Warts (U.K.)Rates of Diagnoses of Genital Warts (U.K.)
0
50
100
150
200
250
300
1972
1974
1976
1978
1980
1982
1984
1986
1988
1990
1992
1994
1996
1998
2000
MalesFemales
Rat
e pe
r 10
0,00
0CDR Weekly 2001; Vol 11(35)
Har vi en Har vi en HPV epidemiHPV epidemi ??
l CIN 3 UK 1993 - 1,45% 2001 - 2,4% + 70%
l Condylomer UK 1971-1994 + 600%
l Seropos. Norge* 1970 2 % 1996 20% + 1000%
l *HPV 16 Dillner 2000, 10 doblet cx cancer uten screening??l Peto J. Lancet 2004: The cervical cancer epidemic that screening has prevented in the UK
HPV HPV relatertrelatert sykdomsykdom i et i et åårskullrskullkvinnerkvinner (n=30.000)(n=30.000)
l 3000 koniseringer (10%)
l 300 med livmorhalskreft ( 1 %)
l 100 dødsfall
l 5000+ kontroller av usikre celleforandringer
l XX Ekstra premature fødsler og senaborter
l 3000 med kjønnsvorter (10 %)
l (120.000 < 16 får ikke vaksine!)
0 %
25 %
50 %
75 %
100 %
93 % 93 % beskyttelsebeskyttelse mot mot celleforandringercelleforandringer (HPV 16 (HPV 16 ogog 18)18)Prevention of HPV 16 or 18Prevention of HPV 16 or 18--related Pap testsrelated Pap tests in Women 16 in Women 16 26 years26 years
N (Gardasil®)= 1021N (Placebo)= 1023
93%
95% CI
85 - 97
8 cases Vaccine108 cases Placebo
ASC-US (positive by high risk probe), LSIL, or worseIversen OE, on behalf of the GARDASIL® Phase II/III Investigators.
EBCOG March 2008
CP RR7946342,7
CP 23-27 uker: RR ca 80
Highest RR 4,4:
24-27 w
N=2164006
N=57136N=15108
Jan2003
Jan2004
Jan2005
Jan2009
Jan2006
Jan2008
Jan2007
Jan2010
Ph III FUTURE I CIN/EGL (N=5455)3
16- to 24-year-old women
Ph II P007 (N=1158)2
Dose-ranging16- to 23-year-old women
Yr 5 Immune MemoryEvaluation
Ph III P016, P018 (N=4836) Safety/Immunogenicity9- to 15-year-old boys and girls5,6
Ph III FUTURE II CIN 2/3 (N=12,167)4
15- to 26-year-old womenDuration of Efficacy Registry StudyNordic Region
Norwegian HPV Surveillance and Disease Burden/Population Effectiveness Study
Ph II P005 (N=2392)1
Proof of Principle 16- to 23-year-old women
Clinical studies on GARDASILClinical studies on GARDASIL
~33,000 subjects enrolledMultinational33 countries
EGL = external genital lesions.GARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
Efficacy in women up to 45 years old6
Efficacy in 16- to 26-year-old men6
1. Koutsky LA, Ault KA, Wheeler CM et al. N Engl J Med. 2002;347:1645 1651. 2. Villa LL, Costa RLR, Petta CA, et al. Lancet Oncol. 2005;6:271 278. 3. Garland SM, Hernandez-Avila M, Wheeler CM, et al. Submitted. 2006 4. FUTURE II study group. Submitted. 2006. 5. Block SL, Nolan T, Sattler C, et al. Submitted. 2006. 6. Data on file, MSD.
Clinical Studies Involving Around 40,000 Clinical Studies Involving Around 40,000 WomenWomen
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Study- 001>1100 women 15-25 yrsEndpoints: Infection/CIN
PII
Study -007: 776 women follow-up
PIII
Study-0132000 adolescentsEndpoints: Safety/immuno
Study-012750 Women 10-25 yrsEndpoints: Consistency & immunobridge PIII
Study-014660 women 15-55 yrsEndpoints: safety/immuno
PIII
Endpoints: CIN/infection
18,666 women 15-25 yrs
-Study-008
PIII
Study-015> 5000 women 26-55 yrsEndpoints: Infection/CIN
PIII
-Study-009
PIII
~12,000 women 18-25 yrs
F
I
L
E
D
A
T
A
Girls 10-14 yrs
Editorial:
Gjennombruddet:
The US evaluation:The US evaluation:
l . . Never before seen vaccines that have close
to 100% efficacy. The data are absolutely
stunning .
Chairman Fed. Adv. Com. on Imm. Pract.
NEJM 16. march 2006, p 1109-11
. . EU member states should lead by making the . . EU member states should lead by making the vaccinations mandatory for all girls aged 11vaccinations mandatory for all girls aged 11--12 years12 years
Viktige spViktige spøørsmrsmåål:l:
l Ikke testet på 12-åringer
l Ikke vist beskyttelse mot kreft
l Kjenner ikke varighet av vaksinen
l Andre HPV typer tar over
HPVHPV--013 Extension Study (Phase III Safety And 013 Extension Study (Phase III Safety And Immunogenicity in Girls Aged 10Immunogenicity in Girls Aged 10 14 Years):14 Years):
l Cervarix® is highly immunogenic in girls aged 10 14 years, inducing 100% seroconversion
through 36 months to date and substantially higher antibody titres than those induced in
women aged 15 25 years, for both HPV-16 and -18. Cervarix® is generally well tolerated in girls aged 10 14 years.
l These data suggest that similar vaccine efficacy against HPV-16- and -18-related virological and clinical outcomes could be expected in early
adolescent females compared with young adult women.l 36 Months Data Rombo L, Dubin G, HPV Vaccine Adolescent Study Investigators. Long-term
safety and immunogenicity of a cervical cancer candidate vaccine in 10- to 14-year old adolescent girls. European Society for Paediatric Infectious Diseases 25th Annual Meeting, Porto. Portugal
2007. Abstract. 97
l Schwarz TF and Decscamps D. Long-term safety and immunogenicity of an AS04 adjuvanted cervical cancer vaccine in girls aged 10 14 years. European Society for Paediatric Infectious
Diseases 26th Annual Meeting 2008. Abstract. 98
Viktige spViktige spøørsmrsmåål:l:
l Ikke testet på 12-åringer
l Ikke vist beskyttelse mot kreft
l Kjenner ikke varighet av vaksinen
l Andre HPV typer tar over
Juni 1987New Zealand
Probability of remaining invasion-free for Group I and II patients at increasing intervals from diagnosis of CIS
(CIN 3 / Ca in situ)
Behandlet
Ubehandlet
% UTENKreft
Viktige spViktige spøørsmrsmåål:l:
l Ikke testet på 12-åringer
l Ikke vist beskyttelse mot kreft
l Kjenner ikke varighet av vaksinen
Vist beskyttelse uten målbare antistoffer
Påvist hukommelsesceller
l Andre HPV typer tar over
Viktige spViktige spøørsmrsmåål:l:
l Ikke testet på 12-åringer
l Ikke vist beskyttelse mot kreft
l Kjenner ikke varighet av vaksinen
l Andre HPV typer tar over
Merck V501 015-20 Konfidential
2000 2005 2010 2015 2020
Time (Years)
Inci
den
ce C
IN 2
/3
(rat
e/10
0,00
0 w
om
en/y
r)
GardasilApproved
(2006)
HPV31
HPV16
Replacement
Cross Protection
Evaluation of Crossprotection or replacement?
Langtids overvLangtids overvååkingkingSynonymer:Synonymer:
l Fase 4 studier
l Post marketing surveillance
l Undersøke om fase 3 resultater bekreftes i
populasjonen
l På norsk: PRØVEKANINER ??
All 12 years old girls to be Research rabbitsAll 12 years old girls to be Research rabbits
20 girls died20 girls died Re HPV vaccineRe HPV vaccine
Norske erfaringer:Norske erfaringer:
l Abortpille - 98
l Nødprevensjon ( Angrepille vs ppille)
l Hjemmeabort
l Nå Rognum/Bioteknologinemnda:
l Hva er alternativet til vaksinasjon. . bevistgjøring, grensesetting, kondom
Viktige spViktige spøørsmrsmåål:l:
l Ikke testet på 12-åringer
l Ikke vist beskyttelse mot kreft
l Kjenner ikke varighet av vaksinen (9 år nå)
l Andre HPV typer tar over
l Vaksinasjon eller ikke? Hva er mest etisk???
Takk for oppmerksomhetenTakk for oppmerksomheten
