



Nonenveloped doublestranded DNA virus 1

>150 types identified 2

~30–40 anogenital types 2,3
~15–20 oncogenic types* ,2,3
› HPV 16 and HPV 18 types cervical cancers.
4
~15-20 nononcogenic** types
HPV 6 and 11 types external anogenital warts.
3
Most Common Sexually
Transmitted Infection
1. Howley PM, Lowy DR. In: Knipe DM, Howley PM, eds. Philadelphia, Pa: Lippincott-Raven; 2001:2197 –2229.
2. Schiffman M, Castle PE. Arch Pathol Lab Med . 2003;127:930
–934. 3. Wiley DJ, Douglas J, Beutner K, et al.
Clin Infect Dis .
2002;35(suppl 2):S210 –S224. 4. Muñoz N, Bosch FX, Castellsagué X, et al. Int J Cancer . 2004;111:278 –285.

The worldwide prevalence of HPV infection is estimated at 9 to 13%
~630 million infected individuals.
1
13.3% 2
Ontario, Canada
15.3% 5
Reims, France
14.5% 3
Morelos State, Mexico
16.6% 4
Concordia, Argentina
40.2% –41.6% 6
Harare, Zimbabwe
18%* ,7
Shanxi Province, China
*Among women 30 –45 years of age
1.
World Health Organization; 2001. Available at: http://www.who.int/vaccines/en/hpvrd/shtml. Accessed July 12, 2004.
2.
Sellors JW, Mahony JB, Kaczorowski J, et al. CMAJ . 2000;163:503 –508. 3.
LazcanoPonce E, Herrero R, Muñoz N, et al. Int J Cancer .
2001;91:412 –420. 4.
Matos E, Loria D, Amestoy GM, et al. Sex Transm Dis . 2003;30:593 –599. 5.
Clavel C, Masure M, Bory JP, et al. Br J Cancer .
2001;84:1616 –1623. 6.
Blumenthal PD, Gaffikin L, Chirenje ZM, McGrath J, Womack S, Shah K. Int J Gynecol Obstet . 2001;72:47 –53. 7.
Belinson
J, Qiao YL, Pretorius R, et al. Gynecol Oncol . 2001;83:439 –444.

Prevalence: 2,274,000 women have cervical cancer 1
Incidence: 510,000 new cases each year 1
510,000 new cases/year
14,845
United States/
Canada
21,596
Central America
49,025
South America
64,928
Europe
67,078
Africa
51,266
Eastern Asia
151,297
Southcentral
Asia
39,648
Southeast
Asia
1077
Australia/
New Zealand
Mortality: Second leading cause of female cancer-related deaths (288,000 annually) 1
1.
World Health Organization. Geneva, Switzerland: World Health Organization; 2003:1
–74.
2.
Bosch FX, de Sanjosé S.
J Natl Cancer Inst Monogr.
2003;31:3 –13.

HPV Type
16 and 18
Approximate Disease Burden
• 70% of cervical cancer
• AIS, CIN 3, VIN 2/3, and VaIN 2/3 cases
• 50% of CIN 2 cases
6 and 11
AIS = adenocarcinoma in situ.
CIN = cervical intraepithelial neoplasia.
VIN = vulvar intraepithelial neoplasia.
VaIN = vaginal intraepithelial neoplasia.
• 90% of genital warts cases
• 35%–50% of all CIN 1, VIN 1, and VaIN 1 cases

HPV Types of Cervical Cancer in Southern
China
( 在中國南部城市引致子宮頸癌的 HPV 種類分佈 )
香港
Lo K PREVALENCE OF HUMAN PAPILLOMAVIRUS IN CERVICAL CANCER: A MULTICENTER STUDY IN CHINA
Int. J. Cancer: 100, 327 –331 (2002)

~510 deaths from cervical, vulvar and vaginal cancers 6
~1835 newly diagnosed cases of cervical, vulvar and vaginal cancers 2,3
Up to 77,000 newly diagnosed cases of genital warts, VIN
VAIN 4,5
>325,000 abnormal Pap tests 1
>4 million Pap tests performed 1
1. Akom E, Venne S. November 2002. 2. Statistics Canada. Table 103-0513. CANSIM [Canadian Cancer Registry].
3. Canadian Cancer Society / National Cancer Institute. Canadian Cancer Statistics 2005:88-9. 4. BC Cancer Agency,
2006. 5. Statistics Canada. Accessed at http://www.40.statcan.ca/101/cst01/demo02.htm
. 6. Statistics Canada. Table
102-0522. CANSIM [Vital Statistics – Death Database].
8

Cervical CancerHong Kong
( 子宮頸癌 香港數據 )
9 th most common female cancer
3 rd top cancer in 25-45 females
Cumulative life time risk = 1 in 129
9 th leading cause of cancer death
376
(2005)
126
(2005)
(Hong Kong) Report of Cancer Expert Working Group on Cancer Prevention and Screening December 2004 http://www3.ha.org.hk/cancereg/eng/cx.pdf
Crude rate = 10.6 per 100,000

Primary - prevention of HPV acquisition
• safer sex practices - # partners, condoms
• prophylactic vaccination
Secondary – prevention of disease
• cervical screening programs
• vulvar, vaginal, anal detection
• treatment of pre-invasive disease
10

Primary - prevention of HPV acquisition
• safer sex practices - # partners, condoms
 prophylactic vaccination
Secondary – prevention of disease
• cervical screening programs
• vulvar, vaginal, anal detection
• treatment of pre-invasive disease
11

~510 deaths from cervical, vulvar and vaginal cancers 6
~1835 newly diagnosed cases of cervical, vulvar and vaginal cancers 2,3
Up to 77,000 newly diagnosed cases of genital warts, VIN, VAIN 4,5
>325,000 abnormal Pap tests 1
>4 million Pap tests performed 1
1. Akom E, Venne S. November 2002. 2. Statistics Canada. Table 103-0513. CANSIM [Canadian Cancer Registry].
3. Canadian Cancer Society / National Cancer Institute. Canadian Cancer Statistics 2005:88-9. 4. BC Cancer Agency,
2006. 5. Statistics Canada. Accessed at http://www.40.statcan.ca/101/cst01/demo02.htm
. 6. Statistics Canada. Table
102-0522. CANSIM [Vital Statistics – Death Database].
12





Most studies have been conducted with women aged 15–26
Clinical trials are now being conducted with mid-adults
Target population for infection
›
›
›
Assuming 1 st sexual intercourse ≤ 15 years of age
Infection occurs soon after first intercourse
Highest prevalence for HPV infections between the ages 15-29 years of age
Primary target population for vaccination
›
›
Female adolescents
Young women

Only women with high number of risk factors
We conclude that targeting individuals based on either the presence or absence of risk factors does
 Will fail to protect many susceptible women vaccination of young adults. Instead, our results comprehensive vaccination of all women in the susceptible to HPV (6, 11, 16, 18), although or social history infection.
 Will fail to protect many women who are susceptible and higher risk of future infection.
Dempsey, et al, Vaccine (2008) 26 , 1111 —1117




244 female university students age 18-22, 2000 -
2006 enrolled within first 3 months of first intercourse with their first male partner excluded from trial if they had a second partner


30% positive for HPV after 1 year
50% positive for HPV after 3 years
HPV Risk by Number of Partners;
Rachel Winer et al,
Univ of Washington, Jan 2008, J Inf Dis
15

Winer, et al, J Infectious Disease, 2007

25.0%
20.0%
15.0%
10.0%
5.0%
0.0%
<26 26-30 31-35 36-40 41-45
Age 年齡
46-50 51-55 >55
Chan et al.
Determinants of cervical human papillomavirus infection: differences between high and low oncogenic risk types.
J Infect Dis 2002; 185: 28-35.
ALL HPV
HR HPV
LR HPV
Other HPV

200
160
120
80
40
0
Age Standardised Prevalence Rate
2000 - 2004
Males
Females
300
200
100
0
600
500
400
Age Specific Prevalence Rate
2000 - 2004
Males
Females
Age
Year
Kliewer E et al. Twenty year trends (1985-2004) in the incidence and prevalence of anogenital warts in Manitoba. Cancer Care Manitoba, 2008.

Age 13-19
1. SY Cheng Sexually Transmitted Infections in Adolescents HK J Paediatr 2002 7 76-84



In Hong Kong, between 3 – 4 thousand patients with genital warts attended the
Social Hygiene Clinic every year in the past decade, which account for about 9% of all attendances
Estimated 30,000 to 40,000 cases per year

The National Advisory Committee on Immunization (NACI) provides the Public
Health Agency of Canada with ongoing and timely medical, scientific and public health advice relating to immunization. The Public Health Agency of Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge.
Members : Dr. M. Naus (Chairperson), Dr. S. Deeks (Executive Secretary), Dr. S. Dobson, Dr. B. Duval, Dr. J.
Embree, Ms. A. Hanrahan, Dr. J. Langley, Dr. K. Laupland, Dr. A. McGeer, Dr. S. McNeil, Dr. M.-N. Primeau, Dr. B.
Tan, Dr. B.Warshawsky.
Liaison Representatives : S. Callery (CHICA), Dr. J. Carsley (CPHA), E. Holmes (CNCI), Dr. B. Larke (CCMOH),
Dr. B. Law (ACCA), Dr. D. Money (SOGC), Dr. P. Orr (AMMI Canada), Dr. S. Rechner (CFPC), Dr. M. Salvadori
(CPS), Dr. J. Smith (CDC), Dr. J. Salzman (CATMAT), Dr. D. Scheifele (CAIRE).

Group
Females
Age 9 –13 years
Females
Age 14 –26 years
Females
Age 14
–26 years with HPV-related cervical or genital disease or current infection
Recommendation Comments

Recommended
•Efficacy is greatest prior to first sexual intercourse
•Although efficacy not demonstrated, immunogenicity data imply high efficacy

Recommended, even after onset of sexual activity
•May not have been infected
•Very unlikely to have been infected with all 4 vaccine HPV types
•Need to be aware that they may already have been infected

Recommended •May not have been infected with vaccine
HPV types
•Very unlikely to have been infected with all 4 vaccine HPV types
•Need to be aware that vaccine probably has no therapeutic effect

Group
Females
Age > 26 years
Females
Age < 9 years
Males
Immunocompromised persons
Pregnancy
Recommendation
 No recommendation can be made
 Not recommended
Comments
•
• Studies are ongoing
• Use can be considered in individual circumstances
No data for this age group
 Cannot be recommended at this time
 Can be given
 Not recommended
• Although immunogenicity data are available, efficacy is as yet unknown
• Immunogenicity and efficacy not known in this population
• Immune response could be weaker
• Data on vaccination in pregnancy is limited
• Pregnant women can complete the vaccination regimen after pregnancy
• No intervention necessary if vaccine was given during pregnancy
15 February 2007

Statement on human papillomavirus vaccine. Canada Communicable Disease Report. An Advisory Committee
Statement (ACS). Can Commun Dis Rep. 2007;33(ACS-2):1-32.

Distribution of HPV positivity (types 6, 11, 16, 18) by serology or PCR among
3,578 North American women aged 16 to 26 years participating in the quadrivalent HPV recombinant vaccine phase II and III clinical trials
Negative to all
4 types: 76.3%
Positive to 1 type: 17.8%
Positive to 2 types: 4.8%
Positive to 3 types: 1.0%
Positive to all 4 types: 0.1%

 vaccine HPV types (16 and 18).
1.1% positive for 3 or more and only 0.1% positive for all four types.
15 February 2007

Statement on human papillomavirus vaccine. Canada Communicable Disease Report. An Advisory Committee
Statement (ACS). Can Commun Dis Rep . 2007;33(ACS-2):1-32.

Multiple Age Groups
• Quebec: Grade 4 & 9, & Girls <18 yrs
• British Columbia: Grade 6 & Grade 9.
• Alberta: Grade 5 & Grade 9 (2009)
• Saskatchewan: Grade 6,Grade 7 catch-up.
New Brunswick: Grade 7,Grade 8 catch-up.
One Age Group
• Manitoba: Grade 6
• Ontario: Grade 8
•
Nova Scotia: Grade 7
•
Prince Edward Island: Grade 6
• Newfoundland and Labrador: Grade 6
Yuk
NWT
Nun
One Age Group
Multiple Age Groups
No Public Announcement
BC
AB
SK
MB QC
ON
NF
NB
PEI
NS
September 2008

 Nova Scotia ~85%
 Prince Edward Island ~80%
 Newfoundland ~75%
 Ontario ~53%
›
Uptake across Ontario varies from 39% to 65% depending on the Public Health
Region.







 Correlate of protective level is unknown
 Measuring or comparing antibody titers is not appropriate for evaluating HPV vaccine efficacy -especially measured in different assays
 WHO Guidelines:
Disease Endpoints (CIN 2/3, AIS or above) are primarily the objectives of HPV vaccine clinical studies.
WHO EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION
Geneva, 23 to 27 October 2006 http://www.who.int/biologicals/publications/trs/areas/vaccines/human_papillomavirus/en/index.html

Ph II –P005 (N=2,392)
Proof of Principle
16- to 23-year-old women
Ph II –P007 (N=1,158)
Dose-ranging
16- to 23-year-old women
Yr 5 Immune Memory
Evaluation
Ph III –FUTURE I CIN/EGL (N=5,455)
16- to 24-year-old women



~29,000 subjects enrolled
Ethnically diverse
33 countries
Ph III –FUTURE II CIN 2/3 (N=12,167)
15- to 26-year-old women
Duration of Efficacy Registry Study
Nordic Region
Norwegian HPV Surveillance and
Disease Burden/Population Effectiveness Study
Ph III –Immunogenicity (N=4,836)
9- to 15-year-old boys and girls
Efficacy in women up to 45 years old
Efficacy in 16- to 26-year-old men
Jan
2003
Jan
2004
Jan
2005
Jan
2006
Jan
2007
FUTURE = Females United to Unilaterally Reduce Endo/Ectocervical Disease
Jan
2008
Jan
2009
Jan
2010

2005 2006 2007
HPV-012 (immuno 10-25y)
HPV-013 (safety/immuno 10-14 yrs)
LT follow-up
LT follow-up
HPV-014 (immuno 15-55y)
2008 2009
LT follow-up
HPV-010 (GSK HPV vaccine vs Gardasil 18-45 yrs)
HPV-001/007 (efficacy in 15-25 yr old women) N = 1113
4.5 yrs 5.5 yrs 6.5 yrs Efficacy
Immunogenicity
Interim analyses virological/histopath endpoints
HPV-009 (efficacy in 18-25 yr old women in Costa Rica) N = 7,462
HPV-008 (efficacy in 15-25 yr old women) N =18,665
Interim analysis CIN2+
HPV-015 (efficacy >25yrs) N=5,700
ACIP Presentation, Dubin, June 28, 2007

Study
Number
Vaccine
Group
Control
Group
Age Range
(years)
Mean Followup
Endpoints
Per-Protocol
Population
(%, 95% CI)
Modified Intention to treat
FUTURE
I (1)
FUTURE
II (2)
2,723
6,087
2,732
6,080
Quadrivalent HPV L1 Vaccine (Types 6, 11, 16, 18)
16-24
15-26
Average 36 months
Average 36 months
CIN 2/3, AIS
GW, VIN 1-3,
VaIN 1-3
CIN 2/3, AIS
100% (CI 94-100)
100%
(CI 94-100)
98% (CI96-100)
Bivalent HPV L1 Vaccine (Types 16, 18)
98% (CI 92-100)
95% (CI 87-99)
95%
(CI 85-99)
PATRICIA
(3)
9,319 9,325 15 - 25 15 months
CIN 1+
CIN 2+
NR
NR
89.2%
(CI 59-99)
90.4
% (CI 53 – 99)

 Multi-center, international study
 Randomization (1:1 ratio) to GARDASIL or placebo (1:1 stratification to 24 to 34 or 35 to 45 year-olds)
 In 3817 24- to 45-year-old women
› No history of LEEP or hysterectomy
› No history of biopsy-diagnosed cervical HPV disease in past 5 years
› No history of genital warts
 Pap testing and cervicovaginal sampling at
~6 month intervals for a total of 48 months
› Colposcopy for ≥ASC-US
Luna, IPV Nov 2007

Combined Incidence of HPV 6/11/16/18-Related Persistent Infection or
Cervical/Vulvar/Vaginal Disease – Per Protocol Efficacy Population
PYR = person years at risk; CI = confidence interval. Luna, IPV Nov 2007







Demonstration of Immune Memory With and Antigen
Challenge at Month 60 with Quadrivalent HPV vaccine
10,000
1000
100
10
0 2 3 6 7 12 18 24 30 36 54
60 61
60 +
1
Olsson SE et al . Vaccine 2007; 25:4931-9.
36

Vaccines’ Long-Term Protection: 4 Examples:
1955 1
Poliovirus Vaccine (Inactivated)
• Recommended to give series of four doses at two, four, and 18 months, and a booster dose at 4 to 6 years 1
•
18-year follow-up shows that vaccine remains effective.
2
• The need for subsequent boosters has not been established.
1
1981 and 1986 1 Hepatitis B Vaccine
1995
• 15-year follow-up shows that vaccine remains effective.
3,4
• Anamnestic response at 5-10 years even when antibodies undetectable.
6,7
•
To date, routine booster is not recommended.
1
1
Hepatitis A Vaccine
•
12-year persistence of antibodies and anamnestic response 5
•
To date, based on mathematical models, it is estimated that the protection could last 20+ years.
1,5
2006
HPV vaccine
•
5 year follow-up shows that vaccine remains effective 8,9
• anamnestic response for the quadrivalent HPV vaccine at 5 years 10
1. Mast E, Mahoney F, Kane M, Margolis H. Hepatitis B vaccine. In: Vaccine, 4 th Ed. Plotkin SA, Orenstein WA editors. Elsevier Inc. USA publisher; 2004. 2. Bottiger M. Vaccine .
1990;8:443 –445. 3. McMahon BJ, Bruden DL, Petersen KM, et al. Ann Intern Med . 2005;142:333 –341. 4. Ni Y-H, Chang M-H, Huang L-M, et al. Ann Intern Med . 2001;135:796 –
800. 5. Van Herck K, Van Damme P, Lievens M, et al. J Med Virol . 2004;72:194 –196. 6. Duval, B., Gilca, V., Boulianne, N., De Waals, P., Masse, P., Trudeau, G. De Serres, G.
Pediatr Inf Dis J. 2005; 24: 213-218. 7. Banatvala, J., Van Damme, P.; Oehen, S. Vaccine. 2001; 19: 877-885. 8. Villa et al British Journal of Cancer (2006) 95, 1459 – 1466
9. Harper, D. et al Lancet (2006) 367: 1247-125510. Olsson S-E et al. Vaccine. 2007; 25: 4931-4939.







A6 Species:
HPV 56-
Related
A7 Species:
HPV 18-
Related
A5 Species:
HPV 51-
Related
A9 Species:
HPV 16-
Related
39
39

Cross-Protection Analysis:
Quadrivalent Vaccine Endpoint:
CIN 2/3 or AIS in Generally HPV-Naïve Women
CIN 2/3 or AIS*
HPV 31/45
HPV
31/33/45/52/58
HPV
31/33/35/39/45/51/
52/56/58/59
Number of cases
GARDASIL 
Number of cases
Placebo
Efficacy
8 21 62%
27
38
48
62
43%
38%
95% CI
10, 85
7, 66
6, 60
Abstract presented by Brown, ICAAC 2007 and Villa, Eurogin 2007

Cross Protection Analysis - Bivalent Vaccine – Phase III
Endpoint – 6 month persistent infection
Type-specific DNA negative at study entry
Group N n
Type 45 Vaccine 6724 10
Vaccine efficacy*
59.9% (2.6 to 85.2)
Type 31
Type 33
Type 52
Type 58
Oncogenic HPV other than vaccine types †
Oncogenic HPV ‡
Control
Vaccine
Control
Vaccine
Control
Vaccine
Control
Vaccine
Control
Vaccine
Control
Vaccine
Control
6747
6615
6667
6702
6736
6532
6573
6688
6734
6773
6804
6773
6804
25
79
116
43
33
505
47
74
31
49
554
545
691
36.1% (0.5 to 59.5)
36.5% (-9.9 to 64.0)
31.6% (3.5 to 51.9)
-31.4% (-132.1 to 24.7)
9.0% (-5.1 to 21.2)
21.9% (10.7 to 31.7)
P
0.0165
0.0173
0.0560
0.0093
0.2515
0.1410
<0.0001
*data are % (97.9% CI)
†HPV types 31,33,35,39,45,51,52,56,58,59,66 and 68.
‡HPV types 16,18,31,33,35,39,45,51,52,56,58,59,66 and 68.
Paavonen et al., Lancet 2007







At diagnosis
Last 12 months
Emotional impact of HPV infection (n=454)
50
40
30
20
10
0
90
80
70
60
Anger Depression Isolation Fear of rejection
Shame Guilt
Clarke P, Ebel C, Catotti DN, Stewart S. Int J STD AIDS. 1996;7:197-200

Senecal et al. IPV 2007

Senecal et al. IPV 2007

›
›
›
›
›
›
›
Sexual discomfort 1
Hot flashes 1
54% between 30 –49 years of age
Vaginal dryness 1
Reproductive concerns (ie, inability to bear children) 1
Fearful of future diagnostic tests and cancer recurrence 1
Cancer-specific distress 1
Sexual-life impairment 2
1. Wenzel L, DeAlba I, Habbal R, et al. Gynecol Oncol . 2005;97:310 –317. 2. Buković D, Strinić T, Habek M, et al. Coll
Antropol . 2003;27:173 –180.







 18,150 16- to 26-year-old women were enrolled in 1 of 3 randomized, placebo-controlled, efficacy trials (protocol 007,
FUTURE I and FUTURE II.
 Pap testing occurred at Day 1 and every 6-12 months for up to 48 months.
 Colposcopy referral was Pap algorithm/HPV test-based.
 Mean follow-up time was ~3.3 years post-dose 1. Case counting began 1 month post-dose 1.

80
60
↓43%
40
20
↓23%
↓16%
↓35%
0
ASC-US HR + LSIL ASC-H HSIL
Cases Placebo 359 1000 89 41
Cases Vaccine 285 864 59 24

60
40
↓42%
↓19%
↓22%
20
0
Colposcopy Cervical Biopsy Definitive therapy
Cases Placebo 1077 950 230
Cases Vaccine 869 741 132

Conclusion
 Administration of quadrivalent HPV vaccine to
HPVnaïve women singificantly reduced the incidence abnormal Pap tests and cervical procedures within only 3.3 years, irrespective of the HPV type involved.
 The highest reductions were observed for HSIL and definitive therapy
 These are the end of study data for the quadrivalent vaccine as the data safety monitoring board recommended vaccination of the placebo arm earlier than planned (FUTURE I and II were planned to last 4 years)

~510 deaths from cervical, vulvar and vaginal cancers 6
~1835 newly diagnosed cases of cervical, vulvar and vaginal cancers 2,3
Up to 77,000 newly diagnosed cases of genital warts, VIN, VAIN 4,5
>325,000 abnormal Pap tests 1
>4 million Pap tests performed 1
1. Akom E, Venne S. November 2002. 2. Statistics Canada. Table 103-0513. CANSIM [Canadian Cancer Registry].
3. Canadian Cancer Society / National Cancer Institute. Canadian Cancer Statistics 2005:88-9. 4. BC Cancer Agency,
2006. 5. Statistics Canada. Accessed at http://www.40.statcan.ca/101/cst01/demo02.htm
. 6. Statistics Canada. Table
102-0522. CANSIM [Vital Statistics – Death Database].
52

Outcome prevented
Genital warts
CIN 1
CIN 2/3
Cervical cancer
Death from cervical cancer
Life-year lost
NNV To prevent 1 Case:
8
5
8
324
729
16
Brisson et al. CMAJ, 2007 1 pg466 table1

•
•
•
•
•
Predicted impact greatest with a school-based program aimed at 12-13 year old girls
High vaccination rates of 86%
Reduction of 16/18 infections by 56% in 2010
Reduction of 16/18 infections by 92% in 2050
Benefits to women of vaccinating males is incremental if the vaccination rates for women stay high
Int.J.Cancer:123, 1854-1863 (2008)
54

Vaccine
HPV (quadrivalent)
Influenza
Meningococcal
Varicella
Estimated NNV to prevent
1 death*
618 1
5,000 2
21,000 3
34,000 4
*assuming vaccine efficacy of 100%
Brisson et al. CMAJ, 2007 1 pg467 co1 pa1

Group
Females
Age > 26 years
Females
Age < 9 years
Males
Immunocompromised persons
Pregnancy
Recommendation
 No recommendation can be made
 Not recommended
Comments
•
• Studies are ongoing
• Use can be considered in individual circumstances
No data for this age group
 Cannot be recommended at this time
 Can be given
 Not recommended
• Although immunogenicity data are available, efficacy is as yet unknown
• Immunogenicity and efficacy not known in this population
• Immune response could be weaker
• Data on vaccination in pregnancy is limited
• Pregnant women can complete the vaccination regimen after pregnancy
• No intervention necessary if vaccine was given during pregnancy
15 February 2007

Statement on human papillomavirus vaccine. Canada Communicable Disease Report. An Advisory Committee
Statement (ACS). Can Commun Dis Rep. 2007;33(ACS-2):1-32.





Multi-center, international study
Randomization (1:1 ratio) to GARDASIL or placebo (1:1 stratification to 24 to 34 or 35 to 45 year-olds)
In 3817 24- to 45-year-old women
›
›
›
No history of LEEP or hysterectomy
No history of biopsy-diagnosed cervical HPV disease in past 5 years
No history of genital warts
Pap testing and cervicovaginal sampling at
~6 month intervals for a total of 48 months
› Colposcopy for ≥ASC-US
Luna, IPV Nov 2007

Combined Incidence of HPV 6/11/16/18-Related Persistent Infection or
Cervical/Vulvar/Vaginal Disease – Per Protocol Efficacy Population
Population
Vaccine Placebo
Cases PYR Cases PYR
All
Subjects
4 2,721 41 2,654
%
Reduction
59% CI P-value
91% 74, 98 <0.001
24 to 34
Year-Olds
2 1,329 24 1,301 92% 67, 99 <0.001
35 to 45
Year-Olds
2 1,393 17 1,353 89% 52, 99 <0.001
PYR = person years at risk; CI = confidence interval. Luna, IPV Nov 2007


As of June 30, 2008, 16 million doses of
Quadrivalent Vaccine given in US and 9,749
VAERS reports of adverse events following vaccination.
›
›
94% were classified as reports of non-serious events
6% as serious events.

Based on the review of available information by FDA and CDC, Gardasil continues to be safe and effective, and its benefits continue to outweigh its risks.







CMAJ, September 9, 2008

“Whether physicians should notify parents of new vaccines depends on whether administration of the vaccine is considered the standard of care by other physicians in the community… Courts might look to standards expressed in accepted medical publications, the common practice of other physicians and recommendations adopted by professional bodies or health organizations.”
New childhood vaccines. Information Letter. December 2002 — Volume Seventeen, Number Four — IL0240E








› Public health vs private sector vs government (family benefits/pharmacare)

10 8 or 9
Having your children immunized
Ensuring that your children eat healthy foods
Making sure that your children wash their hands
Making sure that your children get plenty of physical activity
32%
37%
16%
29%
90%
89%
96%
93%
*On a scale of 0 (not at all important) to 10 (extremely important)
The Canadian Immunization Survey. Ipsos-Reid Healthcare, 2001 .



The Canadian Immunization Survey. Ipsos-Reid Healthcare, 2001


We have an exciting opportunity to make a huge impact in our patients’ lives….

We have the tools to do primary prevention, medicine at its best….

We have center stage as primary care providers to influence the course health care spending from the treatment paradigm to the prevention model…..

And we will….
Thank you!