Sekundärprophylaxe – HPV-Impfung nach Konisation
Elmar A. JouraMedical 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 6,11,16,18-related CIN
Vaccine(N = 8,799)
Placebo(N = 8,800)
nNumber of cases
Rate* nNumber of cases
Rate*Observed efficacy
95% CI
All HPV-Related CIN
2190 4 0.1 2184 32 0.8 87.5 (64.8, 96.8)
By Lesion Type
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)
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.
Subjects Previously Exposed to ≥1 Vaccine HPV Type at Day 1
HPV-Related CIN
Wirksamkeit nach HPV- InfektionenSeropositive Frauen
Vaccine Placebo
CIN n Cases Rate n Cases RateEfficacy
(%)95% CI
HPV 6/11/16/18 1,243 0 0.0 1,283 7 0.2 100.0 (28.7,
100.0)
Vaccine Placebo
GW+VIN n Cases Rate n Cases Rate Efficacy (%)
95% CI
HPV 6/11/16/18 1,268 0 0.0 1,301 8 0.2 100%(39.5, 100.0)
Olsson SE, Vaccine 2009
Prophylaktische WirksamkeitFrauen 24-45a
AgeGardasil Placebo
% Reduction
95% CI P-valueCases pyr Cases pyr
All Subjects
4 2,721 41 2,654 91% 74 – 98 <0.001
24 to 34Year-Olds
2 1,329 24 1,301 92% 67 - 99 <0.001
35 to 45Year-Olds
2 1,393 17 1,353 89% 52 - 99 <0.001
PYR = person years at risk; CI = confidence interval.
Persistant Infection or clinical endpoint related to HPV 6/11/16/18Per-protocol analysis
Munoz et al, Lancet 2009
In situ Carcinome Österreich
6400 Konisationen
30a
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
Melnikow J et al. JNCI J Natl Cancer Inst 2009;101:721-728
Cumulative rates of invasive cervical cancer after CIN
Edgren G et al, Lancet Oncology 2007
Vaginal cancer Vulvar cancer
Incidence of vaginal and vulvar cancers after CIN 3
Edgren G et al, Lancet Oncology 2007
Incidence of anal cancers after CIN 3
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
GARDASIL: FUTURE I/II End-of-Study Results
Incidence of HPV Disease After a Cervical Excisional Procedure1
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
↓46.2%a
↓65%a
Per
cent
Red
uctio
n(9
5% C
I)
(22, 63) (20, 86)
↓47%a
(3.5, 71)
↓79%
(49, 93)
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
Swedish K A et al. Clin Infect Dis. 2012;cid.cir1036
Time to recurrence of high-grade AIN among vaccinated and unvaccinated oncogenic HPV–infected MSM with a history of high-grade AIN (n = 105)
Was ist der biologische Hintergrund dieser klinischen Wirksamkeit?
Schutz gegen anderen HPV- Typ1
Anamnestischer Response in seropositiven
Frauen Impfung verhindert Neuinfektion/ Reaktivierung2,3
Kreuzprotektion: 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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