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The cost effectiveness and real world impact of the quadrivalent HPV vaccine
1. The Cost Effectiveness &
Real World Impact of
Quadrivalent HPV vaccine
Endy M. Moegni
KOGI XV
Bali Nusa Dua Convention Center
29 Juni- 5 Juli 2012
2. Quadrivalent HPV Vaccine
(4 in 1 HPV vaccine)
Diphtheria antitoxin discovered
Measles (live)*
Human Papillomavirus*
Mumps* Zoster (live)*
Measles (live attenuated virus)* Rotavirus*
Measles, mumps, rubella (MMR)*
Pneumococcal (14-valent polysaccharide)*
1895 1963 1967 1968 1971 1977 1978 1981 1983 1986 1989 1995 1996 1996 1996 2005 2006 2006 2006
Measles, mumps, rubella, varicella*
The First Cancer Vaccine Haemophilus influenzae
type b / Hepatitis B*
Haemophilus influenzae type b (liquid)*
of the World Hepatitis A (inactivated)*
Varicella (chicken pox) virus*
Haemophilus influenzae type b (conjugated)*
Hepatitis B (recombinant)*
Pneumococcal (23-valent polysaccharide)*
Hepatitis B (plasma derived)*
Measles, mumps, rubella virus vaccine live (new rubella strain: RA 27/3)*
Tam Kar Fai
3. Cervical Cancer Is Essentially Caused
by Oncogenic HPV
HPV is a main cause of
cervical cancer
Analysis of 932 specimens
from women in 22 countries
indicated prevalence of HPV
DNA in cervical cancers
worldwide = 99.7%.
1. Muñoz N, Bosch FX, de Sanjosé, et al. N Engl J Med. 2003;348:518–527. 2. Walboomers JM, Jacobs MV, Manos
MM, et al. J Pathol. 1999;189:12–19.
4. HPV and Anogenital Warts
HPV 6 and 11
responsible for >90%
of anogenital warts1
Clinically apparent in
~1% of sexually active
US adult population2
Estimated lifetime risk
of developing genital
warts ~10%3,4
Images top left and top right: Reprinted with permission from
NZ DermNet (www.dermnetnz.org)
1. Jansen KU, Shaw AR. Annu Rev Med. 2004;55:319–331. 2. Koutsky L. Am J Med. 1997;102:3–8. 3. Franco EL,
Villa LL, Richardson H, Rohan TE, Ferenczy A. In: Franco EL, Monsonego J, eds. Oxford, UK: Blackwell Science;
1997:14–22. 4. Tortolero-Luna G. Hematol Oncol Clin North Am. 1999;13:245–257, x.
5. Vaginal Intraepithelial Neoplasia
(VaIN)
Main predisposing factor for VaIN is likely exposure to HPV.1
– VaIN is often found in conjunction with cervical intraepithelial
neoplasia (CIN).
1. Winter-Roach B, Monaghan JM, de Lopes A.
Colposcopy of the vagina. In: Bosze P, Luesley
D, eds. EAGC Course Book on Colposcopy.
6. Vulval Intraepithelial Neoplasia
(VIN)
HPV 16 appears to be the dominant HPV type associated with
high-grade VIN (up to 81% in VIN 3)3
– Majority of VIN 1 cases are associated with HPV types 6 and 11 3
– HPV 6, 11, 16, or 18 can be found in VIN 2 or 3 4
Photo courtesy of Dr. J. Monsonego
Photos courtesy of Dr. E.J. Mayeaux
. 3. Buscema J, Naghashfar Z, Sawada E, et al. Obstet Gynecol. 1988;71:601–606. 4. Koutsky L. Am J Med.
1997;102:3–8..
7. VaIN and VIN are of concern because
they are considered as precancerous
lesions with about 40 - 50% associated
with HPV infection
In UK, vulval cancer is 6 times and
vaginal cancer 20 times less common
than cervical cancer1
No screening programme exists
1. Gonzalez Inchaurraga MA et al. HPV and carcinogenesis. Acta Dermatovenerol. 2002;1:1-8.
2. Parkins DM et al. International Agency for Research on Cancer, 2002;8.
9. Infection From Time of First
12 16 20 24 28 32 36 40 44 48 52 56
Sexual Intercourse
Study of female college students (N=603)
Months Since First Intercourse
8
4
0
1.0
0.8
0.6
0.4
0.2
0.0
From Winer RL, Lee S-K, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection:
Incidence and risk factors in a cohort of female university students. Am J Epidemiol. 2003;157:218–226, by
HPV Infection
permission of Oxford University Press.
Cumulative Incidence of
11. Quadrivalent HPV L1 VLP Vaccine1
Quadrivalent HPV L1 VLP vaccine
– (Types 6, 11, 16, 18)
VLPs manufactured in:
– Yeast
– Recombinant VLPs (empty shell protein L1)
– Do not contain Virus DNA (not infectious)
Amorphous Aluminum Hydroxyphosphate
Sulfate Adjuvant (225 μg per dose)
No Mercury preservative (thimerosal)
Storage: 2 to 8 OC
GARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
*VLP = Virus-like particle.
1. Villa LL, Costa RL, Petta CA, et al. Lancet Oncol. 2005;6:271–278.
12. Dosage & Administration
3 doses within 6 months
– (0, 2, 6 months)
0.5mL volume IM injection
Package:
– Prefilled syringe
– Shake well before use
Injection Site:
– Upper arm (Deltoid region)
– Thigh (higher anterolateral area)
13. Gardasil / Silgard Approvals
GARDASIL approved in 127 countries (includes 24 GAVI-eligible)
Europe:
Caribbean & Central America:
North America: Germany Cyprus Ireland
France Czech Republic Latvia
Costa Rica Trinidad/Tobago USA UK Denmark Lithuania
Puerto Rico El Salvador Canada Spain Estonia Luxembourg
Guatemala Honduras Italy Finland Malta Asia Pacific & Japan:
Mexico
Curaçao Nicaragua Austria Greece Netherlands Kyrgyzstan
Bermuda Panama Belgium Hungary Norway Uzbekistan
Bahamas Cayman Islands Bulgaria Iceland Poland Kazakhstan
Barbados Aruba Portugal Romania Slovakia Australia
Jamaica Dominican Republic Slovenia Sweden Serbia Indonesia
Korea
42 Montenegro
Bosnia
Switzerland
Russia
Liechtenstein
Belarus Taiwan
Croatia Turkey Ukraine Hong Kong
South America:
Brazil Bolivia
3 Herzogovina Macedonia Albania Singapore
New Zealand
Argentina Uruguay Macau
Peru
Colombia
Ecuador
Chile
16 35 22
Malaysia
Philippines
Thailand
Paraguay
9 India
Vietnam
Middle East & Africa:
Fiji
Bhutan
Gabon Namibia
Israel C.A.R. Georgia
Morocco Mauritius JAPAN
Kenya Kuwait Sri Lanka
Mauritania UAE Brunei
Guinea Eq. Ethiopia
Uganda Togo
Malawi Congo Brazzaville GAVI – Eligible Registration Approvals (24): Burkina Faso, Cameroon, Central
Jordan Egypt African Republic, Chad, Congo (DR), Cote d’Ivoire, Ethiopia, Guinea (Conakry),
Cote d’Ivoire Burkina Faso India, Kenya, Kyrgyzstan, Malawi, Mali, Mauritania, Nicaragua, Nigeria, Pakistan,
Chad Bahrain Botswana Rwanda, Tanzania, Togo, Uganda, Uzbekistan, Vietnam, Zambia
Lebanon Tanzania Zambia
South Africa Cameroon Nigeria
Pakistan Tunisia Mali
Guinea Conakry Saudi Arabia Rwanda
as of 8 June 2012
14. HPV Recommendations by National Expert Advisory Bodies
on Immunization: 40 Countries
National Funding by 38 Countries 23 Europe
Austria
3 Belgium
Bulgaria
North America Czech Republic
Denmark
USA France
Canada Germany
Mexico Greece
Iceland
Ireland
Italy
Latvia
Luxemburg
Macedonia
Netherlands
2 Norway
Portugal
Caribbean & Central America Romania
Slovenia
Puerto Rico Spain
Panama Sweden
Switzerland
United Kingdom
3 Cayman Is.
South America
Argentina
Peru
Guyana
FUNDING 6
Asia Pacific
GARDASIL only
Australia
Bivalent Only 3 New Zealand
Malaysia
Both vaccines Middle East & Africa
India
No funding Singapore
Kuwait
Japan
UAE
Update: June 8, 2012 Lesotho
15. HPV Vaccine: National Immunization Program
15 countries
Eleven European countries (Germany, France, Italy, Belgium, Austria, Norway, Sweden, Greece, Denmark, Luxemburg
and Switzerland), as well as the United States, Canada, Australia and UK have already reviewed the positive public
health impact and recommended the quadrivalent HPV vaccine for universal human papillomavirus vaccination
with accelerated reviews.
16. Sustained clinical efficacy and antibody titer for at least 5 years
GMT (mMU/mL)
GARDASIL 100%
10 000
Neutralising antibodies
GARDASIL
Clinical efficacy*
1 000
(HPV type 16)
100
10
Natural infection
0 7 12 18 24 30 36 54 60
months 5 years
1st 2nd 3rd
Dose * against infection, CIN (Cervical intraepithelial neoplasia) and genital warts
due to
HPV types 6,11,18; 5 yrs follow up (after dose 1) of a subset (241 women,
Villa L High Sust Eff Proph Quad HPV Vacc 5 Year Followup Br J vaccine
Can 2006 95 1459 & placebo) from a phase II efficacy study
17. Long Term Response
Modified power law model
Conventional power law
model
The conventional power law model estimated a median duration of detectable
antibody of 32 years.
The modified power law model predicted a long-term plateau of antibody
duration with a near life-long persistence above the level of detection.
Model-based prediction of GMTs and proportions above different thresholds following HPV-16 L1 VLP vaccination predicted from the models.
GMTs predicted from the power-law(- - -) and modified power law(—) models, using antibody data measured during 48 months followingHPV-16
L1 VLP vaccination are shown for 30 yrs. 1. C. Fraser et al. / Vaccine 25 (2007) 4324–4333
18. CDC 2010 Mar – Gardasil Q&A for public
Accessed 10 Jul 2010
http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-hpv-gardasil.pdf
20. The near disappearance of genital
warts in young women 4 years after
commencing a national human
papillomavirus (HPV) vaccination
programme
Tim R H Read,1 Jane S Hocking,2 Marcus Y Chen,1 Basil Donovan,3
Catriona S Bradshaw,4 Christopher K Fairley1
21. • From July 2004 to June 2011,
• 52 454 new patients were seen at Melbourne
Sexual Health Centre and 5021 (9.6%, 95% CI
9.3% to 9.8%) were diagnosed with GW.
• From July 2004 to June 2007, the proportions
with GW either increased or did not change in
all groups.
Tim R H Read,1 Jane S Hocking,2 Marcus Y Chen,1 Basil Donovan,3
Catriona S Bradshaw,4 Christopher K Fairley1
23. • The two 12-month periods of 2007/2008 and
2010/2011, GW declined in women under 21
years from 18.6% to 1.9% and in heterosexual
men under 21 years from 22.9% to 2.9%.
• There was no significant change in GW in
women $30 years (OR 0.97, 95% CI 0.84 to
1.12), heterosexual men $30 years (OR 0.97,
95% CI 0.89 to 1.06) or in homosexual men
(OR 0.95, 95% CI 0.85 to 1.07).
Tim R H Read,1 Jane S Hocking,2 Marcus Y Chen,1 Basil Donovan,3
Catriona S Bradshaw,4 Christopher K Fairley1
24. Conclusions
• The dramatic decline and near
disappearance of GW in women and men
under 21 years of age, 4 years after
commencing this programme, suggest
that the basic reproductive rate has fallen
below one.
25. Comparative Cost-Effectiveness of
HPV Vaccines in the Prevention of
Cervical Cancer in Malaysia
• Cost effectivenes
options were compared
for three programs i.e.
screening via Pap
smear; modeling of HPV
vaccination (QV and BV)
and combined strategy
(screening plus
vaccination).
Sharifa WP Ezat1*, Syed Aljunid2
26. Methods
Forthis cross sectional study in 2006-2009
respondents were interviewed from six public
Gynecology-Oncology hospitals. (502 cervical
cancer patients participated).
Methods included expert panel discussions to
estimate treatment costs by severity and
direct interviews with respondents using
costing and quality of life questionnaires.
Sharifa WP Ezat 1*, Syed Aljunid2
27. Results
A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2
years and a mean marriage length of 27.7±12.1 years, Malays accounting for
44.2%.
Cost/quality adjusted life year (QALY) for Pap smear
Cost/quality adjusted life year (QALY) for strategy with HPV vaccination only
Cost/quality adjusted life year (QALY) for strategy with combined strategy
(screening + HPV vaccination)
29. Conclusions
QV is more cost effective than BV.
The QV combined strategy was more
cost effective than any method except
Pap smear screening with high
population coverage.
Sharifa WP Ezat 1*, Syed Aljunid2
30. Comparing Bivalent and Quadrivalent Human Papillomavirus
Vaccines: Economic Evaluation Based on Transmission
Model
Author: Jit et al
31. Results
Effect on disease:
– Use of either vaccine is expected to substantially decrease
the incidence of HPV related cancers regardless of which
scenario is assumed
– By 2109, HPV vaccine may prevent:
Cervical cancer cases vulval, vaginal,
reduction and anal cancers cases
reduction
QHPV 700 (630–800) to 430 (380–490) to
1000 (940–1100) 630 (950–670)
BHPV 730 (650–830) to
1100 (990–1200)
– Use of the qHPV is expected to decrease the incidence of
vaccine type warts and recurrent respiratory papillomatoses
by up to 95% if duration of protection is lifelong.
Jit et al. 2011. BMJ 2011;343:d5775
32.
33. Conclusions
• The quadrivalent vaccine may have an
advantage over the bivalent vaccine in
reducing healthcare costs and QALYs lost .
34. UK switched to QV from Sept 2012
United Kingdom (UK) Department of Health
announced that from next September 2012, UK will
use QV for HPV vaccination program in UK
QV protects against the two types of HPV virus that
cause more than 70 percent of cervical cancer in
England and two types of HPV virus that cause 90
percent of genital warts.
37. References
• Donovan et al. 2010. Quadrivalent human papillomavirus
vaccination and trends in genital warts in Australia: analysis of
national sentinel surveillance data. DOI:10.1016/S1473-
3099(10)70225-5
• Read et al. The near disappearance of genital warts in young
women 4 years after commencing a national human
papillomavirus (HPV) vaccination programme. Sex Transm
Infect. doi:10.1136/sextrans-2011-050234
• Ezat et al. 2011. Comparative Cost-Effectiveness of HPV
Vaccines in the Prevention of Cervical Cancer in Malaysia. Asian
Pacific J Cancer Prev, 11, 1-6.
• Jit et al, Comparing bivalent and quadrivalent human
papillomavirus vaccines: economic evaluation based on
Editor's Notes
Key Point Oncogenic HPV types are the core cause of cervical cancer. Background In a meta-analysis, specific oncogenic HPV types have been identified in 63% – 97% of invasive cervical cancer cases worldwide. 1 Among 85 studies measuring HPV prevalence in invasive cervical cancer by polymerase chain reaction (PCR)–based assays (N=10,058), HPV 16 was the predominant type in squamous cell carcinoma cases (46% – 63%), followed by HPV 18 (10% – 14%), 45 (2% – 8%), 31 (2% – 7%), and 33 (3% – 5%), except in Asia, where HPV 58 and 52 were found in 6% and 4% of cases, respectively. In adenocarcinoma and adenosquamous-carcinoma cases, HPV 18 was predominant (37% – 41%), followed by type 16 (26% – 36%) and type 45 (5% – 7%). The overall detection of HPV DNA in invasive cervical cancer was similar in different regions worldwide. 1 Due to sample inadequacy or integration events effecting the HPV L1 gene, the target of the PCR-based assay, some projected prevalences may actually be underestimated. Walboomers and colleagues conducted a study to more accurately assess the prevalence of HPV DNA. 2 A PCR-based test was used; however, in HPV-negative cases, the biopsy was reanalyzed by a sandwich procedure, in which the inner sections of a series of tissue sections were assayed by 3 different HPV PCR assays targeting different open reading frames, while the outer sections were reviewed to verify the presence of malignant cells. Analysis of 932 specimens from women with cervical cancer in 22 countries indicated that worldwide HPV prevalence in cervical carcinomas is 99.7%. 2 References 1. Clifford GM, Smith JS, Plummer M, Mu ñ oz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: A meta-analysis. Br J Cancer . 2003;88:63 – 73. 2. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol . 1999;189:12 – 19.
Key Point More than 90% of anogenital warts are associated with HPV types 6 and 11. Anogenital warts are clinically apparent in ~1% of the sexually active US adult population. Background More than 90% of anogenital warts are associated with HPV types 6 and 11. 1 The prevalence of anogenital warts has been reported to be highest in women 20 to 24 years of age (6.2 cases/1000 person years) and men 25 to 29 years of age (5.0 cases/1000 person years). 2 About 1% of sexually active adults have clinically apparent genital warts, and at least 15% have subclinical infection. 3 The estimated lifetime risk of developing genital warts is approximately 10%. 4,5 In UK, the number of new cases has been increased over the past 1-2 decades, 32% increase from 1995 to 2004, about 4% of the population reported having been diagnosed to have genital warts, which is the most common STI. References 1. Jansen KU, Shaw AR. Human papillomavirus vaccines and prevention of cervical cancer. Annu Rev Med. 2004;55:319 –331. 2. Insinga RP, Dasbach EJ, Myers ER. The health and economic burden of genital warts in a set of private health plans in the United States. Clin Infect Dis. 2003;36:1397 –1403. 3. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med . 1997;102:3 – 8. 4. Franco EL, Villa LL, Richardson H, Rohan TE, Ferenczy A. Epidemiology of cervical human papillomavirus infection. In: Franco EL, Monsonego J, eds. New Developments in Cervical Cancer Screening and Prevention . Oxford, UK: Blackwell Science; 1997:14–22. 5. Tortolero-Luna G. Epidemiology of genital human papillomavirus. Hematol Oncol Clin North Am . 1999;13:245–257, x.
Key Point The main predisposing factor for VaIN is likely exposure to HPV. VaIN is often asymptomatic and difficult to treat. VaIN can progress to vaginal cancer. Background The true incidence of vaginal intraepithelial neoplasia (VaIN) is unknown but is far lower than for cervical intraepithelial neoplasia (CIN). 1 The incidence of VaIN is expected to rise because of wider application of cytologic screening and colposcopy as well as increased awareness of this disease. 2 The average age of women with VaIN is 35–50 years, which is older than for those presenting with CIN. 2 The main predisposing factor for VaIN is likely to be exposure to HPV, explaining why VaIN is often found in conjunction with CIN. 1 In vaginal smears of 616 women with a prior hysterectomy, vaginal HPV was found 2.4 times more frequently in women with a history of CIN or cervical cancer than in all other women. 3 In addition, of 110 HPV-positive patients, 5 had VaIN, whereas none of the 506 HPV-negative women had VaIN; this difference was statistically significant; all 5 VaIN cases were positive for HPV 16. 3 HPV types 16 and 18 were more often identified in patients with a history of cervical carcinoma; HPV types 6 and 11 were more often seen in patients with a history of benign uterine disease. 3 While untreated VaIN can spontaneously regress, there is a potential for VaIN to progress to invasive vaginal cancer. 2 VaIN is often asymptomatic and difficult to diagnose. A retrospective chart review of 121 women with confirmed histologic diagnosis of VaIN showed that 94% of the patients were asymptomatic; disease was most often identified via an abnormal Pap smear, followed by colposcopy-directed biopsy. 2 Although VaIN is primarily asymptomatic, approximately 80–90% of women with invasive vaginal cancer have symptoms, which may include abnormal vaginal bleeding, abnormal vaginal discharge, a mass that can be felt, or pain during intercourse. 4 References 1. Winter-Roach B, Monaghan JM, de Lopes A. Colposcopy of the vagina. In: Bosze P, Luesley D, eds. EAGC Course Book on Colposcopy . Budapest: Primed-X Press; 2004:120–123. 2. Dodge JA, Eltabbakh GH, Mount SL, Walker RP, Morgan A. Clinical features and risk of recurrence among patients with vaginal intraepithelial neoplasia. Gynecol Oncol. Nov 2001;83:363–369. 3. Schneider A, de Villiers EM, Schneider V. Multifocal squamous neoplasia of the female genital tract: significance of human papillomavirus infection of the vagina after hysterectomy. Obstet Gynecol. Sep 1987;70:294–298. 4. American Cancer Society. Detailed Guide: Vaginal Cancer. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_vaginal_cancer_55.asp?rnav=cri. Accessed August 15, 2006.
Key Point The rate of VIN has been increasing worldwide; and the mean age of women with VIN has decreased from >50 to women in their 30s and 40s. Background The incidence of vulvar intraepithelial neoplasia (VIN) is increasing in the United States and worldwide. 1 The rate of VIN 3 (vulvar carcinoma in situ) in the United States nearly doubled from 1973 to 1987 from 1.1 to 2.1 per 100,000 women-years, surpassing the rate of invasive vulvar cancer. 1 The increased frequency of VIN 3 in the United States has particularly been observed in women less than 35 years of age. 2 The rate has also been increasing worldwide; this increase appears to be associated with HPV infection, especially HPV 16. 1 In the United States, the age of peak incidence of VIN 3 has declined over time from >54 years to between 35 and 54 years. 2 Evidence from outside the United States also suggests that the mean age of women with VIN (including high-grade VIN) is decreasing to <40 years. 3,4 Symptoms occur in the majority of patients with VIN, most commonly pruritus (severe itching), and may be present for a long time prior to diagnosis (median of 1 year). Other symptoms include vulvar pain or soreness, warts, swelling, discoloration, vaginal discharge, or bleeding. 4 References 1. Joura EA. Epidemiology, diagnosis and treatment of vulvar intraepithelial neoplasia. Curr Opin Obstet Gynecol. Feb 2002;14:39–43. 2. Sturgeon SR, Brinton LA, Devesa SS, Kurman RJ. In situ and invasive vulvar cancer incidence trends (1973 to 1987). Am J Obstet Gynecol. 1992;166:1482–1485. 3. Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol. 2005;106:1319–1326. 4. Herod JJ, Shafi MI, Rollason TP, Jordan JA, Luesley DM. Vulvar intraepithelial neoplasia: long term follow up of treated and untreated women. Br J Obstet Gynaecol. 1996;103:446–452.
HPV Phylogenetic Tree Cancer-Causing HPV Species HPV Phylogenetic Tree
Key Point GARDASIL™ is Merck’s quadrivalent HPV L1 VLP vaccine. It is produced in recombinant yeast, like the hepatitis B vaccine, and adsorbed on a proprietary aluminum adjuvant, like the tetanus vaccine. Background Merck’s quadrivalent vaccine has the advantage that it targets 4 HPV types (6, 11, 16 and 18). 1 Together, HPV Types 16 and 18 account for about 70% of cervical cancer and high-grade lesions, whereas HPV Types 6 and 11 are associated with approximately 90% of anogenital warts. 1 Together, these 4 types are responsible for over 40% of low-grade cervical lesions, 2 and HPV 16 and 18 account for over 50% of high-grade lesions. 3 The active quadrivalent vaccine is a mixture of 4 recombinant HPV type-specific VLPs consisting of the L1 major capsid proteins of HPV 6, 11, 16, and 18 synthesized in Saccharomyces cerevisiae. 1 Expression of the L1 protein in yeast generates noninfectious VLPs that resemble HPV virions. 1 A similar method is used for hepatitis B vaccine. 4 The 4 VLP types were purified and absorbed onto amorphous aluminum hydroxyphosphate sulfate adjuvant. 1 The adjuvant dose was 225 micrograms per dose, and the vaccine injection volume was 0.5 mL, given by intramuscular injection at Day 1, Month 2, and Month 6. 1 GARDASIL is a trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA. References 1. Villa LL, Costa RLR, Petta CA, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: A randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol . 2005;6:271–278. 2. Clifford GM, Rana RK, Franceschi S, Smith JS, Gough G, Pimenta JM. Human papillomavirus genotype distribution in low-grade cervical lesions: Comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev . 2005;14:1157–1164. 3. Clifford GM, Smith JS, Plummer M, Muñoz N, Franceschi S. Human papillomavirus types in invasive cervical cancer worldwide: A meta-analysis. Br J Cancer . 2003;88:63–73. 4. Recombivax HB ® Hepatitis B Vaccine (Recombinant) prescribing information. Merck & Co, Inc. Whitehouse Station, NJ. 1998. 3/Recombivax HB/p. 1/ ¶1. 1/Villa/p. 271/col 1/ ¶2 . 1/Villa/p. 272/col 1/ ¶3 . 1/Villa/p. 271/col 2/ ¶1 . 1/Villa/p. 271/col 2/ ¶1 . 1/Villa/p. 272/col 1/ ¶3 . 1/Villa/p. 272/col 2/ ¶1,2 . 2/Clifford/ p.1159/col 2/¶3, table 2 3/Clifford/p.65/ col 2/ ¶2 1/Villa/p. 271/abstract. 1/Villa/p. 272 /col 1/ ¶3. 1/Villa/p. 272 /col 1/¶4. 1/Villa/p. 272 /col 2/¶2. 1/Villa/p. 272 /col 2/¶2.
We want to make it available everywhere Approval vs. Launch * Note: Due to importation, distribution and other regulatory requirements as well as price negotiations, a licensed vaccine may not be marketed in a given country. Registration pending in 26 additional GAVI-eligible countries + WHO pre-qualification submitted Potential Q: which GAVI countries have access to GARDASIL? Indonesia, Kenya and Nicaragua
Messages 100% efficacy lasting for 5 years with antibody titres (neutralising, HPV type specific) plateauing at high level will not drop off tomorrow We therefore expect that Gardasil will protect a long time, 20, may be 30, may be 40 years, may be life-long Comments/Additional information Prevention of Human Papillomavirus infection is essentially through antibodies (neutralising, specific) and not through cell mediated immunity The formulation with 225 μ g of Merck’s aluminium phosphate adjuvant has proven to stimulate high antibody response for Gardasil It is very unusual that vaccines show a higher immune response than natural infection. Gardasil shows ~50 times higher immune response (note that the scale on the left is a log scale!) which is extremely high and exceptional already. Given the 100% efficacy this again shows that there is no sense in trying to induce even higher immune response.
In figure 1, the proportion of new clients with a GW diagnosis was calculated by dividing the number of GW diagnoses by the number of new clients seen in the relevant risk group in 6-month periods. ORs and 95% CIs for a diagnosis of warts in each additional 12-month period after 1 July 2007 were calculated using logistic regression and adjusted for the number of sexual partners in the previous 12 months. The same analysis was also undertaken for the 3-year period from 1 July 2004. These analyses were stratified by different age groups and risk groups. All calculations were performed in Stata V.11 (StataCorp). From 1 July 2004 to 30 June 2011, 52 454 new patients were seen at MSHC and 5021 (9.6%, 95% CI 9.3% to 9.8%) were diagnosed with GWs. The proportion of individuals diagnosed each year with GWs by age and risk group is shown in table 1. The largest declines between the 2007/2008 and 2010/2011 periods occurred in women under 21 years of age (a reduction from 18.6% to 1.9%) and in heterosexual men under 21 years of age (reduction from 22.9% to 2.9%). From 1 July 2010 to 30 June 2011, only four cases of warts occurred in heterosexual women <21 years of age compared with between 46 and 66 cases per annum before July 2007. Figure 1 shows these data in six monthly intervals. Before July 2007, GW diagnoses in women increased significantly with each year (OR 1.16, 95% CI 1.05 to 1.28) and were unchanged in all other groups (table 2). After July 2007, wart diagnoses decreased significantly in women <21 years of age or 22e29 years of age but not older women. Similarly, wart diagnoses decreased in heterosexual men aged <21 years and in those aged 22e29 years but not in older heterosexual men. After July 2007, wart diagnoses did not change in men who have sex with men (MSM) or non-residents. Among women who reported receiving the HPV vaccine, the adjusted OR for a diagnosis of warts was 0.29 (95% CI 0.13 to 0.65) in 2010/2011 compared with 2009/2010.