Efficacité de la vaccination HPV Traitement des condylomes · •HPV 31 - 45 - 52 et 51 ( HPV)...

Efficacité de la vaccination HPV-

Traitement des condylomes

•J. Squifflet•Service de Gynécologie

•Cliniques Universitaires Saint Luc

[email protected]

ECU Mont Godinne, mars 2012

HPV seronegative seropositive

PCR - Naïve Exposition ancienne

PCR+ Infection présenteInfection

présente et /ou chronique

WOMEN > 15:WOMEN > 15: 2,013,133,0002,013,133,000

N CASES > 15:N CASES > 15: 469,723469,723

00 2020 4040 6060 8080 100100

1616 53.553.51818 17.217.2

4545 6.76.73131 2.92.93333 2.62.65252 2.32.35858 2.22.23535 1.41.45959 1.31.35656 1.21.25151 1.01.03939 0.70.76868 0.60.67373 0.50.58282 0.30.3

OtherOther 1.21.2XX 4.44.4

251,199251,19980,85980,85931,54931,54913,67813,67812,13412,13410,92910,92910,24210,2426,5706,570

20,76920,7695,6325,6321,3501,350

6,1376,1375,7695,7694,6414,6413,2113,2112,7142,7142,3392,339

53.5% 53.5% 70.7% 70.7% 77.4% 77.4% 80.3% 80.3% 82.9% 82.9% 85.2% 85.2% 87.4% 87.4% 88.8% 88.8%

All world regions combined

Seronégative etDNA négative

3 Doses

Endpoint group N nVaccine Efficacy (95% CI)

% LL UL P-value

CIN2+ irrespective of HPV type in the lesion

Vaccine 8694 28733.1 22.2 42.6 <0.0001

Control 8708 428


Vaccine 8694 8645.6 28.8 58.7 <0.0001

Control 8708 158

Endpoint Cohort HPV HAVVaccine Efficacy (96.1% CI)

% LL UL P-value


vaccine 8667 22430.4 16.4 42.1 <0.0001

control 8682 322


vaccine 8667 7733.4 9.1 51.5 0.0058

control 8682 116

7

1 End-of-study:

2 Final analysis:

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;

TVC Cohort

Results CIN2+ and CIN3+ Overall efficacy irrespective of HPV type in the lesion

End of study analyse

1 Paavonen et al (IPC - Montreal July 2010)2 Paavonen J et al. Lancet 2009; 374 (9686): 301 - 314

Efficacité sur CIN2+ et CIN3+associés aux types d’HPV vaccinaux et non vaccinaux

(TVC)

Lehtinen M, et al. Lancet Oncol Nov 2011.

Cervarix

Vaccin HAV

Endpoint group N nVaccine Efficacy (95% CI)

% LL UL P-value


vaccine 5466 6164.9 52.7 74.2 <0.0001control 5452 172


vaccine 5466 393.2 78.9 98.7 <0.0001control 5452 44

Endpoint Cohort HPV HAVVaccine Efficacy (96.1% CI)

% LL UL P-value


vaccine 5449 3370.2 54.7 80.9 <0.0001

control 5436 110


vaccine 5449 387.0 54.9 97.7 <0.0001

control 5436 23

10

1 End-of-study:

2 Final analysis:

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;

TVC-naïve Cohort

Results CIN2+ and CIN3+ Overall efficacy irrespective of HPV type in the lesion

End of study analyse

1 Paavonen et al (IPC - Montreal July 2010)2 Paavonen J et al. Lancet 2009; 374 (9686): 301 - 314

Efficacité sur CIN2+ et CIN3+ associée aux types d’HPV vaccinaux et non vaccinaux

(TVC-naïve)

Lehtinen M, et al. Lancet Oncol, Nov 2011.

Dans le groupe vaccin seulement 1 CIN2+ associé

à HPV 16/18

Dans le groupe vaccin seulement 1 CIN2+ associé

à HPV 16/18

• Absolute risk of CIN2+ in women with a normal baseline Pap in relation to concurrent HR HPV status

Risk of progression to CIN2+ is higher in older vs younger HPV+ women

Younger women (22–32 years old) Older women (40–50 years old)

Adapted from Kjaer S, et al. Cancer Res 2006; 66:10630–10636.

HPV +veHPV –ve

HPV +veHPV –ve

Abs

olut

e ris

k of

≥ m

oder

ate

dysp

lasi

a, %

Years of follow-up

0

5

10

15

20

25

30

35

1 2 3 4 5 6 7 8 9 10 11

EFFETS COLLATERAUX….

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

Average follow-up post-therapy: 1.5-1.9 years, Women aged 16-26 years, from protocol 013 and protocol 015

Definitive therapy for cervical disease

(Future I – II studies)

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)

Treatment for GW, VIN or VaIN

(Future I study)

Endpoint Efficacy (%) 95% CI

VaIN1-3, VIN1-3, GWdue to HPV 6/11/16/18 79 (53-92)

VaIN1-3, VIN1-3, GWdue to any HPV type 44 (14,64)

GARDASIL® Efficacy in women aged 16-26 years after definitive therapy (Future I & II) – ITT analysis with case counting after definitive surgery

Efficacy and safety of the bivalent HPV vaccine in women 15–25 years old

HPV 16/18 DNA status /serostatus

HPV 16/18 Endpoint

Vaccinecases (N)

Controlcases (N)

Efficacy*%

96.1% CI

DNA-/sero-

74%1

6-month PI 32 (7,177) 497 (7,122) 93.81,2 91.0–95.912-month PI 21 (7,035) 233 (6,984) 91.21,2 85.9–94.8CIN2+ 4 (7,344) 56 (7,312) 92.91,2 79.9–98.3CIN2+ TAA 1 (7,344) 53 (7,312) 98.11,2 88.4–100.0

DNA-/sero+

13.5% or 10%1

6-month PI 9 (1,462) 47 (1,496) 80.62 58.6–92.012-month PI 2 (1,427) 24 (1,461) 91.52 64.0–99.2CIN2+ 2 (1,510) 6 (1,547) 65.82 -105.7–97.1CIN2+ TAA 0 (1,510) 5 (1,547) 100.02 -22.9–100.0* PATRICIA trial; ATP cohort for efficacy (ATP-E). PI = Persistent infection; TAA = HPV type-assignment algorithm.

• 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

.

High and sustained antibodies above natural infection for at least 8.4 years for both HPV 16 and 18 1-2

Months after 1st

vaccination

Months after 1st

vaccination

HPV

-16

GM

T (E

L.U

/mL)

HPV

-18

GM

T (E

L.U

/mL)

1

10

100

1000

10000

M0 M7 M18 M33-M38

M39-M44

M45-M50

M51-M56

M57-M62

M63-M68

M69-M74

M75-M76

M77-M82

M83-M88

M89-M94

M95-M101

1

10

100

1000

10000

M0 M7 M18 M33-M38

M39-M44

M45-M50

M51-M56

M57-M62

M63-M68

M69-M74

M75-M76

M77-M82

M83-M88

M89-M94

M95-M101

11-fold higher than

natural infection

10-fold higher than

natural infection

HPV-001 HPV-007 HPV-023

Months after 1st

vaccination

Months after 1st

vaccination

HPV

-16

GM

T (E

L.U

/mL)

HPV

-18

GM

T (E

L.U

/mL)

1

10

100

1000

10000

M0 M7 M18 M33-M38

M39-M44

M45-M50

M51-M56

M57-M62

M63-M68

M69-M74

M75-M76

M77-M82

M83-M88

M89-M94

M95-M101

1

10

100

1000

10000

M0 M7 M18 M33-M38

M39-M44

M45-M50

M51-M56

M57-M62

M63-M68

M69-M74

M75-M76

M77-M82

M83-M88

M89-M94

M95-M101

11-fold higher than

natural infection

10-fold higher than

natural infection

HPV-001 HPV-007 HPV-023

HPV 16

HPV 18

1. Rotelli-Martins CM, et al. ESPID 2010; Abstract. 2. Data on File: GSKBio_WWMA_DoF053_1_2010.

Gardasil Cervarix

HPV 16 – 18 – 6 – 11 HPV 16 – 18Cross protection•HPV 31 ( CIN II +)

Cross protection•HPV 31 - 45 - 52 et 51 ( HPV)•HPV 31-33-45- ( CIN II +)

Protection•VaIN – VIN Related HPV•AIN MSM, EGL males

Preliminary data: VIN /VaIN

Long term follow-up•9.5 years

HPV 16 monovalent

Long term follow-up•9.4 years

HPV 16 - 18Immunology – 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?

QALYQuality-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• D T P < 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 $• HPV target: 12 year old girls : 3000 to 45.000 $• 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 QALY1.6/100.000 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

Plummer M, et al. J Infect Dis 2007; 195:1582–1589.

Observed duration of infection (months)

Prop

ortio

n of

per

sist

ent i

nfec

tions

HPV types16525162318918535661average

0 6 12 18 24

1.0

0.8

0.6

0.4

0.2

ASCUS = atypical squamous cells of undetermined significance.

Most infections resolve within 12 months

Traitements des condylomes: « clearance » et « récidives »

Ting et al , 2004

Efficacité de la vaccination HPV Traitement des condylomes · •HPV 31 - 45 - 52 et 51 ( HPV)...

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