Rationalität vs. Emotionen HPV

Report
Sekundärprophylaxe –
HPV-Impfung nach Konisation
Elmar A. Joura
Medical University – Comprehensive Cancer Center Vienna, Austria
Obergurgl, 4 Februar 2013
Outline

Wirkt die HPV-Impfung nur bei jungen Mädchen?

Konisation und Frühgeburtlichkeit

Konisation und Krebsrisiko

HPV- Impfung bei Erkrankten
Prophylactic efficacy against HPV 6,11,16,18related CIN
Subjects Previously Exposed to ≥1 Vaccine HPV Type at Day 1
HPV-Related
CIN
Vaccine
Placebo
(N = 8,799)
(N = 8,800)
n
Number
of cases
Rate*
n
Number
of cases
Rate*
Observed
efficacy
95% CI
2190
4
0.1
2184
32
0.8
87.5
(64.8, 96.8)
CIN 1
2190
4
0.1
2184
27
0.6
85.2
(57.5, 96.2)
CIN 2
2190
0
0.0
2184
7
0.2
100.0
(30.5, 100.0)
CIN 3/AIS
2190
0
0.0
2184
6
0.1
100.0
(14.9, 100.0)
All HPV-Related
CIN
By Lesion Type
Subjects are counted once in each applicable endpoint category. A subject may appear in more than one category.
*Cases per 100 person years at risk.
N = Number of subjects randomized to the respective vaccination group who received at least 1 injection and were seronegative and
PCR negative to the relevant HPV type at enrollment; n = Number of subjects in the given population with at least 1 follow-up visit
following 30 days after Day 1; CIN = cervical intraepithelial neoplasia.
Wirksamkeit nach HPV- Infektionen
Seropositive Frauen
Vaccine
Placebo
CIN
n
Cases
Rate
n
Cases
Rate
Efficacy
(%)
95% CI
HPV 6/11/16/18
1,243
0
0.0
1,283
7
0.2
100.0
(28.7,
100.0)
Rate
Efficacy
(%)
Vaccine
GW+VIN
HPV 6/11/16/18
n
1,268
Cases
0
Olsson SE, Vaccine 2009
Placebo
Rate
0.0
n
1,301
Cases
8
0.2
100%
95% CI
(39.5,
100.0)
Prophylaktische Wirksamkeit
Frauen 24-45a
Persistant Infection or clinical endpoint related to HPV 6/11/16/18
Per-protocol analysis
Age
Gardasil
Placebo
%
95% CI P-value
Reduction
Cases
pyr
Cases
pyr
4
2,721
41
2,654
91%
74 – 98
<0.001
24 to 34
Year-Olds
2
1,329
24
1,301
92%
67 - 99
<0.001
35 to 45
Year-Olds
2
1,393
17
1,353
89%
52 - 99
<0.001
All
Subjects
Munoz
etatal,risk;
Lancet
2009 interval.
PYR = person
years
CI = confidence
In situ Carcinome
Österreich
1200
1000

6400 Konisationen
800
n

30a
600
400
200
0


Gebäralter 
Frühgeburtsrisiko!

Lancet 2006
<50a
>50a
Meta-analysis of relative risk of perinatal mortality
associated with excisional treatment for cervical
intraepithelial neoplasia
Arbyn M et al. BMJ 2008;337:bmj.a1284
©2008 by British Medical Journal Publishing Group
Cumulative rates of invasive cervical
cancer after CIN
Melnikow J et al. JNCI J Natl Cancer Inst 2009;101:721-728
Incidence of vaginal and vulvar cancers after
CIN 3
Vaginal cancer
Edgren G et al, Lancet Oncology 2007
Vulvar cancer
Incidence of anal cancers after CIN 3
Edgren G et al, Lancet Oncology 2007
Fig 1 Study design for assessing effect of quadrivalent HPV vaccine on incidence of
subsequent HPV related disease among women who had undergone surgery for cervical
disease or who were diagnosed with vulvar or vaginal disease.
Joura E A et al. BMJ 2012;344:bmj.e1401
©2012 by British Medical Journal Publishing Group
Fig 2 Participant flow through study.
Joura E A et al. BMJ 2012;344:bmj.e1401
©2012 by British Medical Journal Publishing Group
Fig 3 Incidence of HPV related disease detected ≥60 days after cervical surgery or diagnosis
of vulvar or vaginal disease among women who did not receive quadrivalent HPV vaccine
(that is, placebo recipients).
Joura E A et al. BMJ 2012;344:bmj.e1401
©2012 by British Medical Journal Publishing Group
Fig 4 Time to detection of any HPV related disease (A) or vulvar or vaginal disease (B) after
cervical surgery; and of any HPV related disease (C) or any cervical disease (D) after
diagnosis of vulvar or vaginal disease.
Joura E A et al. BMJ 2012;344:bmj.e1401
©2012 by British Medical Journal Publishing Group
Percent Reduction
(95% CI)
GARDASIL: FUTURE I/II End-of-Study Results
Incidence of HPV Disease After a Cervical Excisional Procedure1
↓79%
↓65%a
↓46.2%a
↓47%a
(22, 63)
(3.5, 71)
(20, 86)
(49, 93)
aIrrespective
of HPV type.
CI = confidence interval; CIN = cervical intraepithelial neoplasia; GW = genital warts; VaIN = vaginal
intraepithelial neoplasia; VIN = vulvar intraepithelial neoplasia.
1. BMJ 2012, Elmar A Joura&al for the Future I and II Study group
17
Cervarix post treatment

Konisation nach Impfung




190 Cervarix
264 Plazebo
1 vs 9 CIN 2+
VE 88% (14.8-99.7)


12 vs 22 CIN 1+
VE 42.6% (-21 – 74)
Garland SM, Eurogin 2011, Lissabon
Time to recurrence of high-grade AIN among vaccinated and
unvaccinated oncogenic HPV–infected MSM with a history of
high-grade AIN (n = 105)
Swedish K A et al. Clin Infect Dis. 2012;cid.cir1036
Was ist der biologische Hintergrund dieser
klinischen Wirksamkeit?

Schutz gegen anderen HPV- Typ1

Anamnestischer Response in seropositiven Frauen


Kreuzprotektion:


Impfung verhindert Neuinfektion/ Reaktivierung2,3
32.5% (95%CI: 6.0, 51.9)4
Kein therapeutischer Effekt!
1) J Infect Dis 2007; 196:1438-1446; 2) Vaccine 2007; 25:4931-4939; 3) Human Vaccines
2009; 5:696-704; 4) J Infect Dis 2009; 199:926-935.
Conclusion





Patienten mit HPV- assoziierten Erkrankungen haben ein
erhöhtes Risiko für weitere Erkrankungen
Frauen nach Konisation haben ein erhöhtes
Karzinomrisiko
HPV- Impfung senkt das Risiko für weitere Erkrankung
signifikant
HPV impfung senkt das Risiko für weitere Konisation um
65-88%
Impfung kann schon vor der Behandlung begonnen
werden!

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