Transcript Le papillomavirus humain et le vaccin contre le PVH en 2006

Don't leave the boys behind:
Update on HPV – 2011
François Boucher
MD, FRCPC
Objectives
After this presentation, participants will be able to:
• Recognize the different manifestations and
complications of HPV.
• Provide appropriate advice on HPV immunization to
families of boys and girls.
• Advocate to public health authorities on the merits
of universal vaccination for HPV
The Human papillomavirus
• DS DNA virus
• Viral genome is episomal
in the host cell
N = 12
• > 200 types
• Classification according to
N = 60
• Tropism
• Cutaneous
• Mucosal (40 types)
• Oncogenicity
• High risk (15)
• Low risk (12)
HPV genotypes
• Tissue tropism
• Cutaneous vs mucosal
• Association with cancer
• Oncogenic
• Non-oncogenic
• Unknown
• 15 types known to be
associated with cancer
• HPV-16: 50% of cancers
• HPV-18: 20%
Neighbor joining phylogenetic tree
of 106 PVs based on CPR region of L1
Park, SB. Lecture Notes in Computer Science. 2003. Vol. 2736.
Cumulative incidence of HPV infection among
women sexually active and HPV negative at
enrollment
Winer RL et al Am J Epidemiol 2003;157:218–226
Estimated life-probability of
acquiring HPV & related morbidity in women
• Genital HPV infection
75%
• Genital condylomas
≥5%
• Abnormal routine Pap test
≥35%
• Invasive cervical cancer
• Communities with routine Pap-testing
<1%
• Communities without routine Pap-testing ~3%
• Other ano-genital cancers
<1%
• Anal cancers in men having sex with men ~3%
• Proportion (~20%) of head/neck cancers <1%
Cumulative incidence of cervical intraepithelial
neoplasia grade 3 and cancer ( ≥ CIN3)
over a 10-year period
20
HPV16+
Cumulative incidence rate (%)
HPV18+
Onc HPV +
15
Onc HPV -
10
5
0
1
2
3
4
5
6
7
8
9
10
11
Follow-up time (years)
Khan MJ et al. JNCI 97:1072
HPV types associated
with cervical lesions by grade
100
90
80
70
HPV 16
HPV 18, 45, 56
HPV 31, 33, 35, 52, 58
HPV 6, 11, 42, 43, 44
60
50
40
30
20
10
0
Normal
CIN 1
CIN 2
CIN 3
Invasive
cancer
Clinical Virology, 2nd edition, 2002, ASM press
Clinical diagnoses associated
with oncogenic HPV
• Cervix
• Cervical intraepithelial neoplasia: CIN 1-2-3
• Adenocarcinoma in situ: AIS
• Vulvovaginal cancers (VIN, VaIN)
• 25-35% associated with HPV
• Anal cancers
• Rare, but increasing in incidence
• 80-90% HPV
• Penile cancers
• 40% HPV
• Neck/ENT cancers
• 25-35% associated with HPV
Burden of HPV disease in men
Heterosexual men
• Prevalence of HPV infection estimated between
25% to 65%
• HITCH study: 56% positive at study entry
MSM
• Overall prevalence is 57%
• Most common type is HPV 16
• Infection independently associated with A)
Receptive anal intercourse [OR 2] and B) 5+ sexual
partners [OR 1.5]
Chin-hong et al, J. Infect dis. 2006
Prevalence of genital HPV infection
in males
Giuliano AR, et al. Cancer Epidemiol Biomarkers. 2008
HPV infection in males
Anogenital warts in Men
• Most common HPV manifestation in men
• Prevalence in Canada (2004):
• 165.2/100 000 in men
• 128.4 in women
• Peak prevalence age
• 25-29 y.o. in men
• 220-24 y.o. in women
Kliewer EV et al. Sex Transm Dis 2009;36:380
Anal cancer: epidemiology
• Uncommon, although increasing in incidence
• 1.9% of all digestive system cancers; 5260 new
cases diagnosed annually (USA)
• Annual incidence: 2.04 (M) and 2.06 (F) per
100,000; higher in black men (1)
• HIV-positive MSM have twice the incidence as that
of HIV-negative MSM
• In the HAART era, anal cancer incidence seems to
increase (quadrupled compared to pre-HAART era
in San Francisco study)(2)
1: Johnson, Cancer 2004
2: Chin-hong et al, J. Infect dis. 2006
Anal and cervical cancer incidences
compared
• Cervical cancer incidence prior to cervical cytology
screening: 40-50/100,0001 (1)
• Cervical cancer currently: 8/100,000
• Anal cancer among HIV- MSM: up to 37/100,000
(2)
• Anal cancer among HIV+ MSM: 137/100,000
person-years since 1996 (3)
1: Qualters JR et al. . MMWR 1992, 41:1-15
2: Daling JR et al. N Engl J Med 1987, 317:973–977
3: D’Souza G et al. J Acquir Immune Defic Syndr. 2008;48(4):491-499
Burden of disease in MSM
HIV-positive
HPV Vaccines
HPV vaccines
Gardasil™ (Merck)
• Reassembled VLP protein L1
• Serotypes 6, 11, 16, 18
• Schedule: 0, 2 & 6 months
• Approved: July 2006
Cervarix™ (GSK)
• Reassembled VLP protein L1
• Serotypes 16, 18
• Schedule: 0, 1 & 6 months
• Approved: February 2010
NACI recommendations 2007
HPV vaccine
• Females 9-13 years of age, as this is before the
onset of sexual intercourse for most females in
Canada, and the efficacy would be greatest
• Females 14-26 years would benefit from the HPV
vaccine, even if they are already sexually active, as
they may not yet have HPV infection and are very
unlikely to have been infected with all four HPV
types in the vaccine.
• Females 14-26 years who have had previous Pap
abnormalities, including cervical cancer, or have
had genital warts or known HPV infection would still
benefit from the HPV vaccine.
Publicly funded
Provincial HPV vaccination programs
Province –
Territory
Recommended schedule
Catchup
SK, MB, PEI, NL,
NU
Females Gr. 6
NB, NS
Females Gr. 7
AB
Females Gr. 5
Gr. 9 in 2009-2012
YT
Females Gr. 6
Free to females 9-26 yrs;
Available for males 9-26 at cost
NT
Females Gr. 4
Gr. 9-12 in 2009-14
ON
Females Gr. 8
QC (2008)
Females Gr. 4 (2 doses 0-6
mo), 3rd year high school (1
dose)
Females < 18 y rs
BC (2010-09)
Females Gr. 6 (2 doses 0-6
mo), Gr. 11 (1 dose)
Females < 18 yrs
http://www.phac-aspc.gc.ca/im/ptimprog-progimpt/table-1-eng.php
Justification for « off-label »
extended schedule
• Immune response to vaccine is strongest in
younger girls
• Data from BCCH affiliated Vaccine Evaluation
Centre confirms two doses of HPV vaccine are
protective due to a strong immune response in girls
9-13 years after two doses given at 0 & 6 months
• Third dose to ensure sustained protection into
sexually active years of life.
• Girls who are known to have immune system
defects associated with solid organ transplant,
stem cell transplant, or HIV infection should receive
HPV vaccine in the three dose schedule at 0, 2 and
6 months.
HPV vaccine coverage in Canada
• Current coverage rates in Canada are considered
suboptimal
• Cultural & religious beliefs
• Public perceptions
• Vaccine program implementation
• HPV vaccine uptake (2008-2009)(1):
• Maritimes: 83%
• QC: 84-87% (the first year…)
• ON: 49%
• AB-MB: 55%
• BC: 66%
1: HPV vaccine can still be a tough sell. Times & Transcript, March 4, 2009
http://timestranscript.canadaeast.com/rss/article/591314
Population effectiveness
• Australia public program since 2007
• 65-75% uptake
• Incidence of AGW in women and men
• 36 055 clients of the Melbourne Sexual Health
Center, 2004-2008
• Decreased incidence in women
≈25%/heterosexual men ≈5% per quarter
• Heterosexual couples study
• www.mcgill.ca/hitchcohort/
• 322 couples
• Decreased incidence of vaccine-type infections
22% vs 7% vaccinated vs unvaccinated
2009 ISTDR: Abstract OS2.9.02
EUROGIN 2010 Abstract No SS 4-6
So, should boys be vaccinated against HPV?
Cost of immunization programs in
Canada over the years
• 1993, boys & girls 0-15 y.o:
• DPT (5 doses); D2T5 (1 ); OPV (4); Hib (3);
MMR (1)
• $83
• 2010, boys & girls 0-15 y.o:
• DTaP-Polio-Hib (4 doses); DTaP-Polio (1); dTaP
(1); PneumoC (3); MenC (1); MMR-V (1); MMR
(1); HBV/HAV (2); Influenza (6-23 mo) (2
doses "primer" + 1)
• $408
• …excluding HPV vaccine…
• ≈50% conjugated pneumococcal vaccine
Cost of immunization programs in the
USA
• 2010, boys & girls 0-15 y.o:
• 30 doses against 16 diseases (excluding
Influenza)
• $1450 for males, $1800 for females
• HPV & meningo ≈ 25%
Vaccine efficacy in men
Giuliano et al., NEJM 2011; 364(5):401
Prevention of HPV 6/11/16/18
infection in men
• 4065 males, aged 16-26 years
• Per protocol efficacy:
• 90.4% reduction in the incidence of HPV
6/11/16/18-related EGL
• 89.4% reduction in condyloma/warts (6/11)
• 85.6% reduction of persistent HPV 6/11/16/18
infection
Giuliano et al., NEJM 2011; 364(5):401
Prevention of anal intraepithelial
neoplasia (AIN) and anal cancer in MSM
• 602/4065 males, aged 16-26 years
• Per protocol efficacy:
• 77.5% reduction in the incidence of HPV
6/11/16/18-related AIN and anal cancer
• 74.9% reduction in high-grade AIN
• 94.9% reduction of persistent HPV 6/11/16/18
infection
Giuliano et al., NEJM 2011; 364(5):401
Cost-effectiveness of HPV vaccination
• Vaccination of 12-year-old girls is cost-effective
• Consistent across models
• Estimates not sensitive to uncertainty in natural
history and epidemiology of HPV
• More uncertainty, less precision in cost-effectiveness
estimates for:
• Vaccination of adult women
• Vaccination of males
Kim JJ. NEJM, October 19, 2011
Chesson H. ACIP, October 10, 2010
Male HPV vaccination
• Estimates of cost-effectiveness of male vaccination
vary
• Within one model when key assumptions are
changed
• Across different models due to differences in
model structure and/or assumptions
• Cost-effectiveness of male vaccination depends on
health outcomes included
• Most favorable scenario is when all potential
health outcomes are included
Chesson H. ACIP, October 10, 2010
Male HPV vaccination
• Cost-effectiveness of male vaccination depends on
vaccine coverage of females
• Most favorable scenario for male vaccination is
when coverage of females is low (1)
• Male vaccination estimated to cost $26,000 (2)
to $62,000 (3) per QALY when female coverage
≤ 50%
1: Brisson M, et al. J Infect Dis. 2011:204 (3): 372
2: Elbasha EH, Dasbach EJ. Vaccine 2010; 28(42): 6858
2: Kim JJ, Goldie SJ. BMJ 2009; 339:b3884
Male HPV vaccination
• Improving vaccine coverage of females may be
more cost-effective than male vaccination
Even if outreach costs are incurred to increase
coverage
• HPV vaccination of MSM is likely to be a costeffective intervention for the prevention of genital
warts and anal cancer
Kim (2010) found cost per QALY $15,000$38,000 over range of assumptions about age at
vaccination and prior exposure to HPV
Kim JJ. Lancet Infectious Diseases, 2010; 10(12):845 - 852
HPV Immunization programs:
Current issues
• Duration of protection in women
• At least five years, probably longer
• Assess need for recall immunization
• Duration of protection in males
• Unknown
• Importance of cross-protection among serotypes
• Different population models are currently being
evaluated for efectiveness & cost-benefit
• Should vaccine valency be increased? If so, which
types should be included?
Should pediatricians recommend HPV
vaccination for boys?
• Pro:
• Safe, efficient and effective vaccine
• Individual protection against AGW and cancers
• Decreased burden of disease & transmission
(evidence of herd immunity)
• Principle of equity
• Parents may ask for it…
• Con:
• Vaccine still very expensive
• Cost-effectiveness still in doubt
• Acceptance will be a challenge
• Parents may oppose it…
http://tinyurl.com/3apx7hh
Merci!
François Boucher
MD, FRCPC