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!