Efficacité de la vaccination HPV

Efficacité de la vaccination HPV
Traitement des condylomes
ECU Mont Godinne, mars 2012
•J. Squifflet
•Service de Gynécologie
•Cliniques Universitaires Saint Luc
jean-luc.squifflet@uclouvain.be
HPV
PCR -
PCR+
seronegative
seropositive
Naïve
Exposition
ancienne
Infection présente
Infection
présente et /ou
chronique
All world regions combined
WOMEN > 15: 2,013,133,000
N CASES > 15:
16
18
53.5
53.5%
70.7%
77.4%
80.3%
82.9%
85.2%
87.4%
88.8%
17.2
45
31
6.7
2.9
33
52
2.6
2.3
58
35
2.2
1.4
59
56
51
39
68
73
82
Other
X
60
80
31,549
13,678
12,134
10,929
10,242
6,570
5,769
1.0
4,641
0.7
3,211
0.6
2,714
0.5
2,339
0.3
1,350
5,632
4.4
40
80,859
1.2
1.2
20
251,199
6,137
1.3
0
469,723
100
20,769
Seronégative et
DNA négative
3 Doses
End of study analyse
Results CIN2+ and CIN3+
Overall efficacy irrespective of HPV type in the lesion
TVC Cohort
1 End-of-study:
Endpoint
group
N
n
CIN2+ irrespective of HPV type in the
lesion
Vaccine
8694
287
Control
8708
428
Vaccine
8694
86
Control
8708
158
Endpoint
Cohort
HPV
HAV
CIN2+ irrespective of HPV type in the
lesion
vaccine
8667
224
control
8682
322
vaccine
8667
77
control
8682
116
CIN3+ irrespective of HPV type in the
lesion
Vaccine Efficacy (95% CI)
%
LL
UL
P-value
33.1
22.2
42.6
<0.0001
45.6
28.8
58.7
<0.0001
2 Final analysis:
CIN3+ irrespective of HPV type in the
lesion
Vaccine Efficacy (96.1% CI)
%
LL
UL
P-value
30.4
16.4
42.1
<0.0001
33.4
9.1
51.5
0.0058
TVC cohort: Population irrespective of HPV DNA and cytological status at baseline;
N = number of evaluable women in each group; n = number of evaluable women reporting at least one event in each group;
1 Paavonen et al (IPC - Montreal July 2010)
2 Paavonen J et al. Lancet 2009; 374 (9686): 301 - 314
7
Efficacité sur CIN2+ et CIN3+
associés aux types d’HPV vaccinaux et non vaccinaux
(TVC)
Lehtinen M, et al. Lancet Oncol Nov 2011.
Vaccin HAV
Cervarix
End of study analyse
Results CIN2+ and CIN3+
Overall efficacy irrespective of HPV type in the lesion
TVC-naïve Cohort
1 End-of-study:
Endpoint
group
N
n
CIN2+ irrespective of HPV type in the
lesion
vaccine
5466
61
control
5452
172
CIN3+ irrespective of HPV type in the
lesion
vaccine
5466
3
control
5452
44
Endpoint
Cohort
HPV
HAV
CIN2+ irrespective of HPV type in the
lesion
vaccine
5449
33
control
5436
110
vaccine
5449
3
control
5436
23
Vaccine Efficacy (95% CI)
%
LL
UL
P-value
64.9
52.7
74.2
<0.0001
93.2
78.9
98.7
<0.0001
2 Final analysis:
CIN3+ irrespective of HPV type in the
lesion
Vaccine Efficacy (96.1% CI)
%
LL
UL
P-value
70.2
54.7
80.9
<0.0001
87.0
54.9
97.7
<0.0001
TVC-naïve cohort: Population naïve to 14 oncogenic HPV types at baseline;
N = number of evaluable women in each group; n = number of evaluable women reporting at least one event in each group;
1 Paavonen et al (IPC - Montreal July 2010)
2 Paavonen J et al. Lancet 2009; 374 (9686): 301 - 314
10
Efficacité sur CIN2+ et CIN3+
associée aux types d’HPV vaccinaux et non vaccinaux
(TVC-naïve)
Dans le groupe
vaccin seulement
1 CIN2+ associé
à HPV 16/18
Lehtinen M, et al. Lancet Oncol, Nov 2011.
Risk of progression to CIN2+ is higher
in older vs younger HPV+ women
• Absolute risk of CIN2+ in women with a normal baseline
Pap in relation to concurrent HR HPV status
Absolute risk of
≥ moderate dysplasia, %
Younger women (22–32 years old)
HPV +ve
HPV –ve
Older women (40–50 years old)
HPV +ve
HPV –ve
35
30
25
20
15
10
5
0
1
2
3
4
5
6
7
Years of follow-up
8
9
10
11
Adapted from Kjaer S, et al. Cancer Res 2006; 66:10630–10636.
EFFETS COLLATERAUX….
GARDASIL® Efficacy in women aged 16-26 years after definitive
therapy (Future I & II) – ITT analysis with case counting after definitive
surgery
Definitive therapy
for cervical disease
(Future I – II studies)
Treatment for GW,
VIN or VaIN
(Future I study)
Endpoint
Efficacy (%)
95% CI
CIN 1 or worse due to HPV
6,11,16,18
74
(<0, 97)
CIN 1 or worse due to
any HPV type
47
(17-66)
Endpoint
Efficacy (%)
95% CI
VaIN1-3, VIN1-3, GW
due to HPV 6/11/16/18
VaIN1-3, VIN1-3, GW
due to any HPV type
79
(53-92)
44
(14,64)
Average follow-up post-therapy: 1.5-1.9 years, Women aged 16-26 years, from protocol 013 and protocol 015
Gardasil® remains efficacious in women who have undergone definitive surgical
therapy and have thereafter developed CIN 1 or worse or external genital lesions
and have had recurrence
Joura E. et al. Abstract presented at ESGO, Belgrade Oct. 2009
Efficacy and safety of the bivalent HPV vaccine in
women 15–25 years old
HPV 16/18
DNA status
/serostatus
DNA-/sero-
74%1
DNA-/sero+
13.5% or
10%1
HPV 16/18
Endpoint
Vaccine
cases (N)
Control
cases (N)
Efficacy*
%
96.1% CI
6-month PI
32 (7,177)
497 (7,122)
93.81,2
91.0–95.9
12-month PI
21 (7,035)
233 (6,984)
91.21,2
85.9–94.8
CIN2+
4 (7,344)
56 (7,312)
92.91,2
79.9–98.3
CIN2+ TAA
1 (7,344)
53 (7,312)
98.11,2
88.4–100.0
6-month PI
9 (1,462)
47 (1,496)
80.62
58.6–92.0
12-month PI
2 (1,427)
24 (1,461)
91.52
64.0–99.2
CIN2+
2 (1,510)
6 (1,547)
65.82
-105.7–97.1
* PATRICIA trial; ATP cohort
for efficacy
infection; TAA
= HPV type-assignment
CIN2+
TAA (ATP-E). PI = Persistent
0 (1,510)
5 (1,547)
100.02algorithm.
-22.9–100.0
•
The bivalent HPV vaccine has been shown to have a clinically acceptable safety profile in
women regardless of their HPV DNA status or serostatus3
1. Paavonen J, et al. Lancet 2009; 374:301–314. 2. FDA. Cervarix®. Vaccines and Related Biological Products Advisory Committee (VRBPAC)
Briefing Document. Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesanOtherBiologics/
VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM181371.pdf. Accessed November 25, 2009. 3. Cervarix®. Europe SPC. December 2009.
Cervical cancer vaccination should be in accordance with the approved Summary of Product Characteristics and with local official recommendations
.
HPV-16 GMT (EL.U/mL)
High and sustained antibodies above natural infection
for at least 8.4 years for both HPV 16 and 18 1-2
10000
HPV 16
1000
11-fold
higher
than
natural
infection
100
10
1
HPV-18 GMT (EL.U/mL)
M0
M7
M18
M33M38
M39M44
M45M50
M51M56
10000
M57- M63M62 M68
M69M74
M75- M77M76 M82
M83M88
M89- M95M94 M101
Months after 1st
vaccination
HPV 18
1000
10-fold
higher
than
natural
infection
100
10
1
M0
M7
HPV-001
M18
M33M38
M39M44
M45M50
M51M56
M57M62
HPV-007
M63M68
M69M74
M75M76
M77M82
M83M88
M89- M95M94 M101
HPV-023
1. Rotelli-Martins CM, et al. ESPID 2010; Abstract. 2. Data on File: GSKBio_WWMA_DoF053_1_2010.
Months after 1st
vaccination
Gardasil
Cervarix
HPV 16 – 18 – 6 – 11
HPV 16 – 18
Cross protection
•HPV 31 ( CIN II +)
Cross protection
•HPV 31 - 45 - 52 et 51 ( HPV)
•HPV 31-33-45- ( CIN II +)
Preliminary data: VIN /VaIN
Protection
•VaIN – VIN Related HPV
•AIN MSM, EGL males
Long term follow-up
Long term follow-up
•9.5 years
•9.4 years
HPV 16 monovalent
HPV 16 - 18
Immunology – immune response
Antibodies
Coût efficacité
• Efficacité
• Durée d’éfficacité
• Effets secondaires
• Quelles patient(e)s?
Coût du vaccin, coût des soins de
santé, nombre de cancer du col de
l’utérus dans le pays, autres cancers
HPV « dépendant », hommes?
QALY
Quality-Adjusted Life Year
Account for quality and lenght of life
• One year in perfect health = 1 QALY
• Death = 0 QALY
• One year of live in less than perfect health is
given a value between = 0 and 1 QALY
Cost per QALY gained by vaccines in the US
•
•
•
•
•
•
•
•
•
DTP
< 0 (cost saving)
Hib
< 0 (cost saving)
MMR
< 0 (cost saving)
Polio
< 0 (cost saving)
Varicella
< 0 (cost saving)
Influenza
 10.000 $
HAV
~ 10.000 – 30.000 $
3000 to 45.000 $
HPV target: 12 year old girls :
HAV and HBV target: college freshmen: < 0 – 10.000 $
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• Nombre cancer col : efficience du dépistage
• Effets collatéraux :
– Condylomes
– Protection croisée
– Cancers HPV dépendants (vulve, vagin, anus,ORL,…)
• Vaccination garçons :
– Couverture filles
– Certains groupes
• Booster
• Efficacité du vaccin
• Compliance vaccin - dépistage
Cost effective
• Ratio of Euro per quality-adjusted life year (QUALY)
• Netherlands:
– Ratio of 53.500 € per QALY (118 €/injection)
– Ratio of 20.000 € (40 €/injection)
• If booster (33 €/injection)
• If 4 boosters (16 €/injection)
Threshold: 20.000 € per QALY
1.6/100.000 women year
HPV vaccination is not cost effective
Vaccination HPV :coût- efficacité
• Vaccins efficaces, suivi à long terme (rappel,
effets secondaires, effets collatéraux, …)
• Coûts à réduire
• Améliorer la couverture
• (Ré)organisation du dépistage
• Les Naïves les premières……
Resolution of prevalent HPV infections by
viral type at entry in women with ASCUS
Proportion of persistent infections
1.0
HPV types
16
52
51
62
31
89
18
53
56
61
average
0.8
0.6
0.4
Most infections
resolve within 12
months
0.2
0
6
12
18
24
Observed duration of infection (months)
ASCUS = atypical squamous cells of undetermined significance.
Plummer M, et al. J Infect Dis 2007; 195:1582–1589.
Traitements des condylomes: « clearance » et « récidives »
Ting et al , 2004