Download HPV-vaccines

HPV-vaccines
–
a breakthrough in medicine
Björn Strander
Onkologiskt centrum Västra regionen
and Kungsbacka Närsjukhus
Sweden
Cervical cancer
”Unusual complication to
persistent infection with high
risk HPV”
2 vaccines
• Gardasil – MSD
– Quadrivalent HPV 6,11,16,18
– Approved by European agency in september
2006
• Cervarix – GSK
– Bivalent HPV 16, 18
– Approved by European agency in september
2007
VLP vaccines
High antibody levels – VLPs injected i.m.
give good access to lymphatics and draining
lymph nodes where antibody responses are
initiated and memory cells develop
VLPs are very immunogenic, activating
antigen presenting cells and B- and T-cells
Duration of Efficacy Evaluation
• The duration of efficacy of HPV-vaccines have
not been determined
• High efficacy of vaccines was observed through
4,5 - 5 years of follow-up
• Minimum protective anti-HPV level has not been
defined
– No breakthroughs due to waning immunity
– Antibodies remain quite stable through 4,5 - 5 years
• Vaccines induces immune memory responses
HPV 16/18-Related Cervical, Vulvar, Vaginal
Cancer Efficacy (Via Surrogates)
Per-Protocol Efficacy Population
HPV
16/18Related
Follow up 3 years
Gardasil
Placebo
%
Efficacy
CIN 2/3 or
AIS
1
42
98
86, 100
VIN 2/3 or
VAIN 2/3
0
15
100
72, 100
95% CI
Evidence of cross reactivity
• Gardasil: 38% efficacy against CIN2+
containing 10 non-16/18 high risk HPVtypes
• Cervarix: 27% protection against 12
months persistent infection with 12 non16/18 hrHPV-types
Efficacy for all CIN2+ in population neg HPV
6/11/16/18 and with negativ cytologi at
baseline
2.4 years follow up
Expected Efficacy without cross reactivity= 99% x 0.52 = 51%
Endpoint
Gardasil
Cases
CIN2-3 or AIS
52
Placebo
%
Cases Efficacy
97
46
95% CI
24, 62
Conclusion Efficacy Gardasil
Follow up > 2 years
HPV naïve
Mixed ITT
population
HPV 16/18related CIN2+
-99%
-41%
All CIN 2+
-46%
-17%
Conclusion Efficacy Cervarix
Follow up 15 months
HPV naïve
HPV 16/18related CIN2+
All CIN 2+
Mixed ITT
population
- 90 –
100%
No data
No data
No data
Sweden
• Life time risk for cervical cancer 0.7%
• Can be reduced to 0.25% with screening +
vaccination
• NNT for preventing 1 case of cervical
cancer ~ 200
• NNT for saving 1 life ~ 600
1
• Other estimates 618 - 1125
1
Brisson et al CMAJ aug 2007
Numbers needed to vaccinate to
save one life
• Varicellae
• Meningococcus
• Influenza
34 000
21 000
5 000
Vaccinating people > 65 years of age
HPV and cancer
Cancer
% associated
HPV
HPV 16/18
Number in
Sweden 2005
Cervix
≥95%
70%
429
Vagina
60%
55%
46
Vulva
40%
30%
128
Penis
40%
25%
80
Anus
90%
80%
130
Head and neck
20%
18%
579
Number of female cancers that could be
prevented with HPV 16/18 vaccination
Non-cervical in proportion of cervical cancers
489
63 %
Parkin, Bray Vaccine. 2006 Aug 21;24
Socialstyrelsen Cancerstatistik www.sos.se Accessed 070315
1.
2.
HPV vaccines
Advantages – world wide
• Breakthrough in prevention of cervical
cancer
• Can offer the protection for third world
women with minimum side effects
• Can have dramatic effect on incidence and
mortality on a world scale
HPV vaccines
Advantages – Nordic countries
• Mass vaccination of girls in school can reach
those who will not attend screening
• Will reduce mortality in cerival cancer
• Less treatment of cancer and dysplasia will give
benefits in fertility and pregnancy losses
• Reduced anxiety associated with cancer and
dysplasia
• Reduction of other cancers are to expect
• Reduction of warts (Gardasil)
• Not more serious adverse events than placebo
• Boys/men can benefit from herd immunity
HPV vaccines
Concerns
• Cost
• Prevent improvement of existing
screening?
• Need of booster vaccination?
• Efficacy against cancer?
– will type replacement occur?
• Implementation in the third world
– women hostile cultures