Papillomavirussen en vaccinatie - WordPress.com...Papillomavirussen en vaccinatie Prof. Dr. Marc Van...
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VAKB Symposium, 8 februari 2011 Papillomavirussen en vaccinatie Prof. Dr. Marc Van Ranst KULeuven
Transcript of Papillomavirussen en vaccinatie - WordPress.com...Papillomavirussen en vaccinatie Prof. Dr. Marc Van...
VAKB Symposium, 8 februari 2011
Papillomavirussenen vaccinatie
Prof. Dr. Marc Van RanstKULeuven
Virologie en classificatievan papillomavirussen
circulair dsDNA
Early proteins
Lateproteins
PpPV-1
Hamlet (march 8, 2003)
Hamlet (march 8, 2003)
Cher (march 8, 2003)
PHYLOGENETIC CLASSIFICATIONOF HUMAN PAPILLOMAVIRUSES
HPV-1
HPV-25HPV-20
HPV-14HPV-21HPV-5HPV-47
HPV-8HPV-2HPV-57
HPV-6HPV-11
HPV-13HPV-44
HPV-43HPV-42
HPV-16HPV-35
HPV-31
HPV-52HPV-33
HPV-58
HPV-51
HPV-56
HPV-18
HPV-45HPV-39MF180
Van Ranst et al., J Gen Virol. 1992
CUTANEOUS BENIGN PAPILLOMAVIRUSES:
WARTS (VERRUCA)
PHYLOGENETIC CLASSIFICATIONOF HUMAN PAPILLOMAVIRUSES
HPV-1
HPV-25HPV-20
HPV-14HPV-21HPV-5HPV-47
HPV-8HPV-2HPV-57
HPV-6HPV-11
HPV-13HPV-44
HPV-43HPV-42
HPV-16HPV-35
HPV-31
HPV-52HPV-33
HPV-58
HPV-51
HPV-56
HPV-18
HPV-45HPV-39MF180
CUTANEOUS TROPISM
Van Ranst et al., J Gen Virol. 1992
VERRUCA VULGARIS: HPV-2
CUTANEOUS MALIGNANT PAPILLOMAVIRUSES:
EPIDERMODYSPLASIA VERRUCIFORMIS (EV)
PHYLOGENETIC CLASSIFICATIONOF HUMAN PAPILLOMAVIRUSES
HPV-1
HPV-25HPV-20
HPV-14HPV-21HPV-5HPV-47
HPV-8HPV-2HPV-57
HPV-6HPV-11
HPV-13HPV-44
HPV-43HPV-42
HPV-16HPV-35
HPV-31
HPV-52HPV-33
HPV-58
HPV-51
HPV-56
HPV-18
HPV-45HPV-39MF180
CUTANEOUS TROPISM
Van Ranst et al., J Gen Virol. 1992
EPIDERMODYSPLASIA VERRUCIFORMIS
Gross, Human Papillomavirus Infection: A Clinical Atlas,
1997
MUCOSAL LOW-RISK PAPILLOMAVIRUSES
GENITAL WARTS (CONDYLOMATA)
PHYLOGENETIC CLASSIFICATIONOF HUMAN PAPILLOMAVIRUSES
HPV-1
HPV-25HPV-20
HPV-14HPV-21HPV-5HPV-47
HPV-8HPV-2HPV-57
HPV-6HPV-11
HPV-13HPV-44
HPV-43HPV-42
HPV-16HPV-35
HPV-31
HPV-52HPV-33
HPV-58
HPV-51
HPV-56
HPV-18
HPV-45HPV-39MF180
Van Ranst et al., J Gen Virol. 1992
CUTANEOUS TROPISM
LOW-RISK MUCOSAL
HIGH-RISK MUCOSAL
CONDYLOMATA ACUMINATA
MUCOSAL HIGH-RISK PAPILLOMAVIRUSES
CERVICAL INTRAEPITHELIAL
NEOPLASIA (CIN) AND CERVICAL CANCER
PHYLOGENETIC CLASSIFICATIONOF HUMAN PAPILLOMAVIRUSES
HPV-1
HPV-25HPV-20
HPV-14HPV-21HPV-5HPV-47
HPV-8HPV-2HPV-57
HPV-6HPV-11
HPV-13HPV-44
HPV-43HPV-42
HPV-16HPV-35
HPV-31
HPV-52HPV-33
HPV-58
HPV-51
HPV-56
HPV-18
HPV-45HPV-39MF180
Van Ranst et al., J Gen Virol. 1992
CUTANEOUS TROPISM
LOW-RISK MUCOSAL
HIGH-RISK MUCOSAL
HYSTERECTOMIE
Stenchever, Atlas of clinical gynecology, 1990
HPV vaccinatie
IMMUNOLOGIE VAN HPV
• Infectie is beperkt tot mucosa: geen
viremie
• Weinig contact met immuunsysteem !
• Natuurlijke infectie geeft slechts lage
antistoftiters tegen L1
• T-cel immuniteit verantwoordelijk voor
natuurlijke regressie van letsels: andere
antigenen dan L1
Schiller and Hildesheim, 2000
IMMUNOLOGIE VAN HPV
• IgG-gemedieerde humorale immuniteit
verantwoordelijk voor preventie van
letsels: vooral tegen L1 antigeen
• IgG belangrijker dan locale IgA productie
• Transudatie van IgG in cervicale mucosa
na intramusculaire injectie van L1 VLPs
• Goeie correlatie tussen serum IgG levels
en mucosale IgG levels
GARDASIL
CERVARIX
16 18 6 11
16 18
Schiller and Hildesheim, 2000
LONG-TERM IMMUNITY ?Cervarix against HPV-16: >8 years (and counting)
LONG-TERM IMMUNITY ?Cervarix against HPV-18: >8 years (and counting)
LONG-TERM IMMUNITY ?Gardasil against HPV-16: >5 years (and counting)
LONG-TERM IMMUNITY ?Gardasil against HPV-18: >5 years (and counting)
COMPARISON CERVARIX/GARDASIL(2 years after vaccination)
Einstein et al., Human Vaccines, 2010
LONG-TERM IMMUNITY ?
Einstein et al., Human Vaccines, 2010
LONG-TERM IMMUNITY ?COMPARISON CERVARIX/GARDASIL
(2 years after vaccination)
0
10
20
30
40
50
60
70
80
90
100
ATPATP ATP ITT ITT
96%95% 100% 96% 100%
Harper et al. Lancet 2006; 367: 1247-55
6M Persistent
Infection
12M Persistent Infection (post hoc analysis 001 Initial
efficacy study )
Cytology CINIncident
Infection
Cervarix efficacy (%) after 4.5 yearsHPV-16/18 associated
Initial efficacy study (001) 001 / 007 combined analysis
92% 100% 93% 0/6100%
ATP ATP ITT ITTATP
LONG-TERM PROTECTION ?
Rowhani-Rahbar et al., Vaccine 2009
LONG-TERM PROTECTION ?
>30 years ?
1
10
100
1000
0 5 10 15 20 25 30
Years After Vaccination
GM
T (
mM
U/m
l)
LONG-TERM PROTECTION ?
HPV-16
HPV-35
HPV-31
HPV-52
HPV-33
HPV-58
HPV-51
HPV-56
HPV-18
HPV-45
HPV-39
MF180
CROSS-PROTECTION ?
Cervarix: Skinner et al., 2009 (Malmö Conference)
HPV 31
HPV 33
HPV 45
6 monthpersistence
CIN2+
77% (66-85)
43% (19-61)
81% (64-91)
100% (78-100)
72% (19-92)
100% (-19-100)
CROSS-PROTECTION ?
GARDASIL
Brown et al., FUTURE study, ICAAC, 2007
CROSS-PROTECTION ?
• Na introductie van vaccin toch blijvende cervixscreening !
• Algemene vaccinatie meisjes 10-13j via schoolgezondheidszorg
• Vrouwen tussen 14 en 26 jaar die nog geen seksueel contact hebben gehad
• Vrouwen tussen 14 en 26 jaar die reeds sexuele betrekkingen gehad hebben
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0
1
2
3
4
5
0 10 20 30 40 50 60 70 80 90 100
Time in Years
Inci
den
ce p
er 1
00,0
00 .
No Vaccination
12-yo females
12-yo females+females catch up
12-yo females&males
12-yo females&males+females catch up
12-yo females&males+females and males catch up
IMPACT OF VACCINATION ON CERVICAL CANCER
Elamin H. Elbasha
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0
25
50
75
100
0 10 20 30 40 50 60 70 80 90 100
Time in Years
Inci
den
ce p
er 1
00,0
00 . No Vaccination
12-yo females
12-yo females+females catch up
12-yo females&males
12-yo females&males+females catch up
12-yo females&males+females and males catch up
IMPACT OF VACCINATION ON HPV16/18 CIN 2/3
Elamin H. Elbasha
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0
20
40
60
80
100
120
140
160
0 10 20 30 40 50 60 70 80 90 100
Time in Years
Inci
den
ce p
er 1
00,0
00 .
No Vaccination
12-yo females
12-yo females+females catch up
12-yo females&males
12-yo females&males+females catch up
12-yo females&males+females and males catch up
IMPACT OF VACCINATION ON GENITAL WARTS
Elamin H. Elbasha
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IMPACT OF VACCINATION ON GENITAL WARTS
Fairley et al., Sexually Transmitted Infections, 2009: Melbourne Sexual Health Center
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