Title: A Cost-Effectiveness Analysis of Alternative Human papillomavirus (HPV) Vaccination Strategies
1A Cost-Effectiveness Analysis of Alternative
Human papillomavirus (HPV) Vaccination Strategies
- Elamin H. Elbasha
- Merck Research Laboratories, USA
2Presentation outline
- HPV infection and disease
- HPV vaccines
- Merck model
- Public health impact
- Economic impact
- Summary and conclusions
3HPV infection
- HPV is small, non-enveloped, encapsulated,
double-stranded DNA virus - HPV encodes two structural proteins
- L1 codes for major capsid protein
- L2 codes for minor capsid proteins
- Enormous HPV diversity
- More than 100 HPV genotypes
- More than 40 types infect ano-genital tract
- At least 13 high-risk types cause cervical cancer
- Ubiquitous
- Lifetime Risk of HPV infection up to 70 among
sexually active - Major risk factor for HPV acquisition number of
sexual partners
4Neoplasm or external genital warts
Asymptomatic or common warts
5HPV infection life cycle
Goodman A., Wilbur D. C. Case 32-2003 A
37-Year-Old Woman with Atypical Squamous Cells on
a Papanicolaou Smear. N Engl J Med 2003
3491555-1564
6Conditions associated with HPV types 16, 18, 6,11
- HPV 16, 18 Estimated attributable
- Cervical cancer 70
- High grade cervical abnormalities 50
- Low grade cervical abnormalities 30
- Anal cancer 70
- Vulva / Vagina / Penile 40
- Head and neck cancers 3-12
- HPV 6, 11
- Low grade cervical abnormalities 10
- Genital warts 90
- Recurrent respiratory papillomatosis (RRP) 90
Clifford, BJ Ca 2003 Munoz Int J Cancer 2004
Brown J Clin Micro 1993 Carter Cancer Res 2001
Clifford Cancer Epi Biomarkers Prev 2005 Gissman
Proc Natl Acad Science 1983 Kreimer Cancer
Epidemiol Biomarkers Prev 2005
7By end of presentation, 16 women would die from
cervical cancer
Second most common cancer among women 274,000
deaths from cervical cancer in 2002
Globocan 2002
8Immunologic Basis for HPV vaccines
- L1 HPV major capsid protein self-assembles into
empty virus-like particles (VLPs) - In animal models of papillomavirus infection
using species-specific VLPs - Vaccination results in protection from infection
and disease - Efficacy associated with development of
neutralizing antibodies - Transfer of serum from vaccinated to unvaccinated
animals transfers protective efficacy - Protection is prophylactic, not likely to be
therapeutic - Protection is likely to be type-specific
9HPV vaccines
- Prepared from virus-like particles
(non-infectious) - Produced by recombinant technology
- Do not contain any live biological product or DNA
- GARDASIL prophylactic quadrivalent HPV
(6,11,16,18) vaccine licensed in U.S. other
countries - First vaccine to prevent cervical cancer,
precancerous genital lesions, and genital warts - Series of three injections over a six-month
period - Safe and highly efficacious
- CERVARIX prophylactic bivalent HPV (16,18)
vaccine in final stages of clinical testing
10Research questions
- What are the epidemiologic consequences of HPV
vaccination? - What is the sensitivity of vaccine health impact
(HPV, CIN, cervical cancer, genital warts) to - vaccine characteristics (e.g., duration of
protection)? - vaccination strategies (females and males,
females-only, catch-up, etc.)? - What is the cost-effectiveness of programs using
a quadrivalent HPV (6/11/16/18) vaccine?
11Methods
- Direct and indirect herd immunity effects of
vaccination - Describe transmission of the virus and resulting
disease in a population - Assess impact of vaccine on vaccinees and their
contacts - An integrated disease transmission model and
cost-utility analysis - Demographic model
- Behavioral model
- HPV infection and disease models
- Economic model
- US healthcare system data and perspective
- Assumes existing screening practices
12Transfer diagram, no vaccine compartments
13Transfer diagram, vaccine compartments
14Transfer diagram, CIN compartments
15Vaccine characteristics data and assumptions
- Vaccine take ( of vaccinees with vaccine effect)
- HPV 16/18 100, HPV 6/11 100
- Vaccine degree of protection
- HPV 16/18, HPV 6/11 against infection 90
(CI74?100) - HPV 16/18, HPV 6/11 against disease 100
(CI87?100) - Vaccine duration of protection
- HPV 16/18, HPV 6/11 10 years to lifetime
- Breakthrough infections
- Infectiousness and clearance same as natural
infections
16Vaccination strategies
Description Definition
A. Routine 12-year-old females Vaccinate females before reaching age 12
B. Routine 12-year-old females and males Vaccinate females and males before reaching age 12
C. 12-year-old females 1224-year-old females catch-up Strategy A a temporary catch-up program targeting 1224-year-old females
D. 12-year-old females and males 1224-year-old females catch-up Strategy B a temporary catch-up program targeting 1224-year-old females
E. 12-year-old females and males 1224-year-old females and males catch-up Strategy B a temporary catch-up program targeting 1224-year-old females and males
17Vaccination penetration rates assumptions
- Routine 12-year olds
- increase vaccine penetration linearly from 0 in
Year 0 to 70 in Year 5 and after - Catch-up 12?24-year olds
- All cohorts (12?24) increase vaccine penetration
linearly from 0 in Year 0 to 50 in Year 5 - Program stops after 5 years
18Impact of vaccination strategies diagnosed HPV
16/18-related cervical cancer incidence, females
(12y), lifelong duration
19Impact of vaccination strategies diagnosed HPV
16/18-related CIN 2/3 incidence- females (12y)
lifelong duration
20Impact of vaccination strategies diagnosed HPV
6/11/16/18-related CIN 1 incidence - females
(12y) lifelong duration
21Impact of vaccination strategies diagnosed HPV
6/11-related genital warts incidence - females
(12y) lifelong duration
22Impact of vaccination strategies diagnosed HPV
6/11-related genital warts incidence - males
(12y) lifelong duration of protection
23Cumulative quality-adjusted life years
24Cumulative costs
25Cost-effectiveness analysis of HPV vaccination
strategies
Discounted total Discounted total Incremental Incremental Incremental
Strategy Costs QALYs Costs QALYs /QALYs
No vaccination 72,659,302 2,698,711
12-year-old females 74,042,990 2,699,178 1,383,687 467 2,964
12-year-old females and males 78,707,825 2,699,327 4,664,835 149 dominated
12-year-old females 12?24-year-old females catch up 74,815,667 2,699,343 3,892,159 16 4,666
12-year-old females and males 12?24-year-old females catch up 79,746,357 2,699,461 4,930,690 118 41,803
12-year-old females and males 12?24-year-old females and males catch up 81,761,210 2,699,506 2,014,853 45 45,056
Assumes cost of vaccination series is 360 and
duration of protection is lifelong. Compared
with the preceding non-dominated strategy.
26Sensitivity analysis Impact of vaccination
strategiesdiagnosed HPV 16/18-related CIN 2/3
incidence- females (12y) 10-years duration vs.
lifetime
27Impact of Vaccination StrategyCervical Cancer
Incidence - Females (1285y) Lifelong duration,
50 coverage
28Impact of Vaccination StrategyCervical Cancer
Incidence - Females (1285y) Lifelong duration,
90 coverage
29Sensitivity analyses Incremental
cost-effectiveness ratio (/QALY) vs. duration of
protection cost
Input range/Program Vaccination costs Vaccination costs
Input range/Program 300 500
Vaccine duration of protection lifelong
12-year-old females 12?24-year-old females catch up 2,422 9,900
12-year-old females males 12?24-year-old females males catch up 36,161 65,810
Vaccine duration of protection 10-Years
12-year-old females 12?24-year-old females catch up 16,194 32,619
12-year-old females males 12?24-year-old females males catch up 44,562 79,115
30Sensitivity analyses Incremental
cost-effectiveness ratio (/QALY) vs. vaccine
coverage and cost
Input range/Program Vaccination costs Vaccination costs
Input range/Program 300 500
Vaccine coverage 50
12-year-old females 12?24-year-old females catch up 2,056 9,271
12-year-old females males 12?24-year-old females males catch up 28,845 53,479
Vaccine coverage 90
12-year-old females 12?24-year-old females catch up 2,925 10,739
12-year-old females males 12?24-year-old females males catch up 82,241 142,830
31Limitations outstanding research questions
- Vaccine characteristics (e.g., duration of
protection) are influential - Need more and better epidemiologic and natural
history of disease data to support model - Need to analyze the impact on other important
HPV-related diseases such as vulvar and vaginal
neoplasias and cancers, recurrent respiratory
papillomatosis - Need to reflect the indirect costs of HPV-related
disease - Need to model HPV types interaction/cross
protection - If screening practices change, the model can
reflect the shifting impact of vaccination
32Summary
- A prophylactic quadrivalent HPV vaccine can
substantially reduce the incidence of cervical
cancer, CIN, and genital warts - Catch up vaccination can provide earlier and
greater reductions in HPV-related disease - Vaccinating males and females before age 12
combined with a temporary 12?24-year olds catch
up program can be cost-effective and efficiently
added to current screening programs
33Acknowledgement
- Erik J. Dasbach, PhD
- Ralph P. Insinga, PhD
- Merck Research Laboratories, USA