Context Recently published results suggest that effective vaccines against cervical
cancer—associated human papillomavirus (HPV) may become available within
the next decade.
Objective To examine the potential health and economic effects of an HPV vaccine
in a setting of existing screening.
Design, Setting, and Population A Markov model was used to estimate the lifetime (age 12-85 years) costs
and life expectancy of a hypothetical cohort of women screened for cervical
cancer in the United States. Three strategies were compared: (1) vaccination
only; (2) conventional cytological screening only; and (3) vaccination followed
by screening. Two of the strategies incorporated a vaccine targeted against
a defined proportion of high-risk (oncogenic) HPV types. Screening intervals
of 1, 2, 3, and 5 years and starting ages for screening of 18, 22, 24, 26,
and 30 years were chosen for 2 of the strategies (conventional cytological
screening only and vaccination followed by screening).
Main Outcome Measures Incremental cost per life-year gained.
Results Vaccination only or adding vaccination to screening conducted every
3 and 5 years was not cost-effective. However, at more frequent screening
intervals, strategies combining vaccination and screening were preferred.
Vaccination plus biennial screening delayed until age 24 years had the most
attractive cost-effectiveness ratio ($44 889) compared with screening
only beginning at age 18 years and conducted every 3 years. However, the strategy
of vaccination with annual screening beginning at age 18 years had the largest
overall reduction in cancer incidence and mortality at a cost of $236 250
per life-year gained compared with vaccination and annual screening beginning
at age 22 years. The cost-effectiveness of vaccination plus delayed screening
was highly sensitive to age of vaccination, duration of vaccine efficacy,
and cost of vaccination.
Conclusions Vaccination for HPV in combination with screening can be a cost-effective
health intervention, but it depends on maintaining effectiveness during the
ages of peak oncogenic HPV incidence. Identifying the optimal age for vaccination
should be a top research priority.
The vast majority of cervical cancer is caused by persistent infection
with cancer-associated human papillomavirus (termed oncogenic or high-risk HPV).1,2 By
identifying and treating cervical intraepithelial neoplasia (CIN), the cervical
cancer precursor lesion associated with HPV infection, screening programs
based on cytology have reduced the incidence of invasive cervical cancer.3
Because the majority of invasive cervical cancer and cervical neoplasia
can be attributed to infection with a subset of HPV types, including HPV 16,
HPV 18, HPV 31, and HPV 45,2 a prophylactic
vaccine to prevent infection with 1 or more of these types has the potential
to substantially reduce the incidence of cervical cancer and its precursor
lesions. Recent results from a phase 2 trial of a vaccine targeted against
HPV 16 showed 100% (95% confidence interval, 90%-100%) efficacy over a median
follow-up of 17.4 months in preventing HPV 16–specific persistent infection
or CIN.4 Larger phase 3 trials of vaccines
targeted against multiple oncogenic types are under way. Because clinical
trials are limited in their ability to explore the impact of vaccination on
long-term outcomes and results may not be available for some time, mathematical
modeling can be used to identify those variables that may have the greatest
impact on the cost and benefits associated with vaccination, as well as suggest
potential strategies for incorporating an effective vaccine into existing
screening programs.5,6
Several well-validated models of the natural history of cervical cancer
have been developed and used to evaluate various screening strategies.7-12 Consistent
themes have emerged from the use of these models. First, as screening frequency
increases, the cost-effectiveness ratios increase dramatically due to increased
detection of transient cervical abnormalities and associated low-grade CIN
lesions. These transient lesions are primarily observed in younger women,
which explains the second consistent finding: delaying screening until the
mid-30s is a more efficient strategy for reducing cancer mortality.7,11,13 In addition, screening
appears to be less effective against rapidly progressing cancers, with proportionately
smaller reductions in cancer incidence in younger women compared with women
in their 40s and 50s.7,14 These
findings suggest that the costs of HPV vaccination might be partly offset
by savings achieved by delaying the age of beginning screening and by screening
less frequently.
In this study, we used mathematical modeling to explore potential strategies
for combining existing secondary prevention methods for cervical cancer with
primary prevention using an effective HPV vaccine.
We used a previously described health state-transition Markov model
to simulate the natural history of HPV infection and cervical cancer: relevant
parameters were derived from a published systematic review and are described
in detail elsewhere.7,8,12,15 The
model was revised to separately simulate high- and low-risk HPV infection.16
In these analyses, we simulated a cohort of girls beginning at age 12
years (and followed-up until age 85 years), who, at the start of the simulation,
had never had sex and were disease-free. Each year, they faced an age-specific
risk of acquiring high-risk or low-risk HPV infection that could either persist,
progress (to CIN 1 or CIN 2-3), or resolve. Those who developed CIN 1 or CIN
2-3 could have their disease persist, regress, or progress. Women with cancer
(International Federation of Gynecology and Obstetrics stages I, II, III,
or IV) could have their disease detected if they presented for a gynecologic
examination based on their symptoms. If not, they could either progress to
the next stage or remain in the same stage. Each year, women faced age-specific
risks of dying from other causes or of having a hysterectomy for indications
unrelated to cervical neoplasia. Additional health states were defined to
distinguish women who had prior treatment for CIN, were cancer survivors,
or had died due to cervical cancer.
We made several simplifying base-case assumptions about the natural
history of high-risk HPV infection, which were tested in sensitivity analyses.
First, we assumed that HPV infection progression to CIN 1 and CIN 2-3 was
not differentially affected by an HPV vaccine. Because there is some evidence
that infection with oncogenic HPV types, particularly HPV 16, is more likely
to progress directly to CIN 2-3 (referred to as rapidly
progressing infections),7,8,17,18 we
tested 2 different implications of our base-case assumption: (1) all rapidly
progressing infections that result in CIN 2-3 lesions would be eliminated
as a result of vaccination or (2) none of the rapidly progressing infections
would be affected by vaccination. Second, we assumed in the base case that
the vaccine would be targeted at a proportion of high-risk HPV types rather
than 1 or 2 high-risk types and that this proportion would be constant as
the cohort aged. However, depending on the particular HPV type targeted (eg,
HPV 16), the contribution to the overall age-specific incidence might vary
as a function of age. We therefore tested this assumption by increasing or
decreasing the proportion of high-risk types that the vaccine targets as a
function of age.
For the base case, we used the model to estimate the cost and life expectancy
associated with 3 strategies, under the assumption that an effective vaccine
targeted at a defined proportion of high-risk HPV types was available: (1)
1-time vaccination of 12-year-old girls only; (2) conventional cytology-based
screening only; and (3) 1-time vaccination of 12-year-old girls followed by
cytology-based screening. Screening was performed at intervals of 1, 2, 3,
and 5 years. Because American Cancer Society guidelines19 for
the optimal age of onset of screening have been recently revised, we varied
the age of screening onset from 18 to 22, 24, 26, and 30 years.
Females were chosen as the target group because of current trial design,
in which initial regulatory approval for a vaccine is likely to be limited
to females (E. Barr, oral communication, February 12, 2002). Because HPV is
a common sexually transmitted infection, we assumed that vaccination would
be most effective if targeted toward girls prior to the onset of sexual activity.
Vaccination at age 12 years was chosen for the base case because data suggest
that very little sexual activity has taken place by this age.20
We made several base-case assumptions for screening and treatment, all
of which were subsequently tested in sensitivity analyses (Table 1). First, we assumed, as have others, that compliance with
primary screening,9 follow-up, and treatment10 was 100%. Second, conventional cytology was chosen
because its test characteristics are better characterized than liquid cytology.7 Based on published systematic reviews and primary
screening studies, we assumed that conventional cytology had a sensitivity
of 55.6% and specificity of 95.7% for detection of ≥CIN 2-3.21-23 Although
liquid cytology is commonly believed to have superior sensitivity to conventional
cytology, recent studies suggest that improvements may be less than previously
thought.24-26 We
varied the sensitivity and specificity of cytology to account for this uncertainty.
Third, we did not use the recent revision to the Bethesda system because data
on its performance in practice are not yet available,27 and
previous studies have concluded that new categorizations for atypical squamous
cells of undetermined significance (ASCUS) do not have substantial effects
in terms of clinical outcomes.9 Fourth, women
with ASCUS were managed by repeat cytology in 6 months' time; women with abnormal
results (ASCUS or more severe result) had colposcopy performed. Although baseline
data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade
Squamous Intraepithelial Lesions Triage Study28 suggest
that use of HPV testing may be superior to repeat cytology in the detection
of high-grade lesions, we did not specifically evaluate the use of currently
available HPV tests because of a lack of data on how type-specific vaccination
might affect the characteristics of HPV tests that do not identify specific
types. Fifth, we assumed that colposcopy was performed for all cytological
results of low-grade squamous intraepithelial lesion, high-grade squamous
intraepithelial lesion, or cancer. Sixth, we assumed that colposcopy had perfect
sensitivity and specificity for detection of ≥CIN 2-3; this assumption
was tested in sensitivity analysis. Seventh, we assumed that those with no
underlying disease confirmed at colposcopy returned to routine screening.
Eighth, we assumed that women with treated CIN received annual screening for
the remainder of their lifetime, or until hysterectomy for other indications.
Ninth, we assumed that women with invasive cancer had their cancer staged
and received stage-appropriate treatment. Finally, Hughes et al29 have
suggested that successful, aggressive treatment of CIN detected during screening
may reduce a treated woman's risk of cancer because nonlesional tissue that
is susceptible to infection with HPV also is removed. In the model, for the
base case, we assumed that women who were screened and successfully treated
would have a 95% reduction in risk of developing CIN, but varied this assumption
in sensitivity analyses.
As with screening and treatment, we made several initial assumptions
that were tested in sensitivity analyses. First, we assumed that vaccination
and therefore vaccine efficacy was limited to the cohort itself. Thus, reductions
in cancer were assumed to be due to reduced susceptibility to infection rather
than due to a reduction in sexual transmission of HPV. Second, we assumed
that a vaccine to prevent HPV infection in a US population would be targeted
at more than 1 type to have a significant impact (>50%) on cancer and allow
for a change in current screening policies. As such, we assumed the vaccine
would be targeted against 70% of oncogenic HPV types, including HPV 16 and
HPV 18. Third, we assumed vaccine efficacy was 90%, representing the lower
bound of the 95% confidence interval for the recently published HPV 16 vaccine
trial.4 Fourth, efficacy was modeled as a proportionate
reduction in the age-specific incidence of high-risk HPV. Fifth, the duration
of vaccine efficacy was constant over 10 years and then was assumed to decrease
to zero efficacy for the base case. Sixth, there were no significant adverse
effects due to vaccination. Seventh, the entire cohort of 12-year-old girls
was vaccinated once (with a 3-series vaccine) and all girls were successfully
immunized.
Base-case direct medical cost estimates for screening and diagnoses
were derived from MEDSTAT, the National Ambulatory Medical Care Survey, and
Medicare data.7 We assumed that the vaccine
would be administered within current health care visits so that there would
be no programmatic costs. Vaccine costs ($200) were based on an Institute
of Medicine report on future vaccine development30 and
were assumed to include all direct medical costs associated with a 3-vaccine
series. Because the inclusion of indirect costs associated with screening
might be expected to favor vaccination, we examined the inclusion of indirect
costs for screening in sensitivity analyses only using estimates derived from
the published literature.9,10 The
indirect costs for vaccination used in sensitivity analyses were estimated
as the costs for parent time taken for 3 office visits. We also examined the
impact of including the cost for 1 or more booster series to increase vaccine
duration in sensitivity analyses. All costs were expressed in 2001 US dollars
using the medical care component of the consumer price index from the Bureau
of Labor statistics.
Health-Related Quality of Life
There are currently no published utilities that are applicable to all
states associated with cervical cancer screening and prevention. Because assumptions
about which states to include and the value of utilities for these states
can have a substantial impact on cost-effectiveness ratios,31 we
did not include health-related quality of life in the base case. However,
to provide comparability with other published results, quality-adjusted life
expectancy was calculated in sensitivity analyses using utilities derived
from the literature (Table 1).9,10 The disutility of having CIN 1 or
≥CIN 2-3 detected through screening was conservatively assumed to last
for 1 month. The utilities for cancer were assumed to apply during the first
5 years of follow-up. After 5 years, a cancer survivor was assumed to have
a utility of 1, corresponding to perfect health.
Analytic Strategy and Sensitivity Analyses
We calculated incremental cost-effectiveness ratios in which the additional
costs of a strategy divided by the additional savings in life expectancy or
quality-adjusted life expectancy were compared with the next, less costly
strategy. Strategies were considered dominated if they were more costly and
less effective (in terms of life expectancy) than an adjacent strategy or
strategies. We also calculated the expected reductions in CIN, cancer incidence
(all stages), and/or mortality for key sensitivity analyses. We adjusted future
costs and life expectancy to current values by discounting them at 3% annually.32 In the base case, we did not include nonmedical costs
or quality-of-life measures. In sensitivity analyses, we used a broader societal
perspective and included nonmedical costs and quality-of-life measures.
The face validity of our model has been previously confirmed by comparing
the age-specific HPV, CIN, and cancer incidence curves with population-based
data that were not used to create the model.8 The
age-specific high-risk HPV incidence curve has a peak within an age range
and of similar magnitude to that reported in the literature.33,34 The
lifetime risk of 3.5% for incident cervical cancer predicted by the model
is similar to that reported in the literature.9,10 In
the absence of screening or vaccination, our model predicts mean discounted
lifetime cost of $207 and life expectancy of 28.56 years for a cohort of 13-year-olds,
which are similar to the $210 lifetime cost and life expectancy of 28.70 years
reported by Kim et al.9 The incremental cost-effectiveness
ratios associated with different screening intervals for cytology only are
of similar magnitude to those reported by Kim et al9 and
Mandelblatt et al10 when run using similar
parameters and assumptions.
Natural History of HPV and Cervical Cancer With and Without Vaccination
Figure 1A shows the predicted
prevalence of oncogenic HPV (all types) with and without vaccination, using
base-case assumptions, varying the duration of vaccine efficacy from 5 years
to a lifetime, or assuming a gradual waning in vaccine efficacy. The model
predicts a lowered prevalence of oncogenic HPV when a longer duration of vaccine
efficacy is assumed or a gradual waning of efficacy is assumed instead of
a blunt drop to 0. Figure 1B shows
the projected impact of vaccination alone in terms of reducing cervical cancer
incidence; results for cervical cancer mortality were similar (data not shown).
For the base case, the model projects that vaccination will result in a reduction
in cancer incidence (all stages) of 16.8% and a 17.7% reduction in cervical
cancer deaths compared with no intervention.
In initial analyses, we examined 40 strategies comparing screening only
conducted every 1, 2, 3, and 5 years with a strategy of screening plus vaccination
at identical intervals, varying the ages of screening onset (age 18 years,
22 years, 24 years, 26 years, and 30 years). Results from these initial analyses
suggested that vaccination with screening would be cost-effective if the onset
of screening for this combined strategy could be delayed relative to screening
only. We assumed that implementation of a cost-effective policy including
vaccination with a delayed age for screening onset would likely only be acceptable
to policy makers, clinicians, and patients if it did not result in excess
cancer mortality. As such, we defined a minimal acceptable efficacy for the
strategy of vaccination and screening compared with screening alone by identifying
an age for each screening interval beyond which a delay in the onset of screening
would result in more cervical cancer deaths than a strategy of screening only.
For simplification, we fixed the age of first screening for screening only
to age 18 years. These delayed ages of first screening were 30 years for screening
every 5 years, 26 years for screening every 3 years, 24 years for screening
every 2 years, and 22 years for screening annually. For every interval, we
theorized that this delayed age for first screening would result in a higher
mean life expectancy at a reasonable cost for vaccination combined with delayed
screening compared with screening only at age 18 years. First, our definition
of a delayed age at first screening usually meant slightly fewer deaths (Table 2). Second, vaccination with delayed
screening would result in fewer cancer deaths in younger women (5% fewer cancer
deaths would occur in women aged ≤26 years when vaccination and delayed
screening conducted every 2 years beginning at age 24 years was compared with
screening alone conducted at the same interval beginning at age 18 years),
which led to larger gains in mean life expectancy. Lastly, for the same comparison,
55% fewer CIN 1 lesions would be detected and treated among screened women
aged 30 years or younger, thus avoiding the costs associated with detecting
and treating lesions that were more likely to regress. As a result, from the
initial 40 strategies, we focused our analyses on 12, including a strategy
of vaccination and screening beginning at age 18 years.
Figure 2 depicts the discounted
lifetime cost and life expectancy associated with the 12 strategies, as well
as a strategy of vaccination only. The efficiency curve includes only strategies
that dominate those to the right, either because they are more effective and
less costly, or have a more attractive cost-effectiveness ratio compared with
the next best strategy. As shown, a strategy of vaccination only would not
be cost-effective. Focusing on those strategies on the efficiency curve, screening
only was preferred at less frequent screening intervals (every 5 years and
every 3 years). The strategy of screening only every 5 years beginning at
age 18 years had an incremental cost-effectiveness ratio of $6030 per life-year
gained compared with no intervention. The incremental cost-effectiveness ratio
for the same strategy conducted every 3 years was $21 912. At more frequent
screening intervals (every 2 years or annually), a combination of vaccination
and screening was preferred with incremental cost-effectiveness ratios ranging
from $44 889 (for vaccination and screening beginning at age 24 years
and conducted every 2 years compared with screening only conducted every 3
years) to $236 250 (for vaccination and screening beginning at age 18
years and conducted every year compared with the same strategy and interval
beginning at age 22 years). These results are also summarized in Table 2.
Using $50 000 per life-year saved as a threshold,35 vaccination
plus biennial screening beginning at age 24 years appeared to be the most
attractive strategy (Table 2).
We therefore focused our sensitivity analyses around this screening interval
to identify the assumptions and ranges for variables that had the largest
impact on the cost-effectiveness ratio of this strategy compared with screening
only every 2 years beginning at age 18 years.
Univariate analyses indicated that the age at which the cohort could
receive vaccination could be delayed until age 15 years without compromising
life-expectancy gains, given patterns of sexual activity and HPV acquisition. Table 3 shows the results of other univariate
sensitivity analyses on key natural history, vaccination, screening, and treatment
variables (base-case assumptions are presented in Table 1). Overall, values for parameters resulting in greater overall
vaccine effectiveness (proportion of the population who receive vaccination
and are successfully immunized, proportion of HPV types covered, vaccine efficacy,
vaccine duration) resulted in more attractive cost-effectiveness ratios or
dominance for vaccination plus delayed screening. If the same efficacy and
duration of efficacy as that used in the base case could only be achieved
using a booster (at age 17 years), the cost of vaccination with delayed screening
would increase to more than $300 000 per life-year gained compared with
screening only every 2 years beginning at age 18 years. Addition of a booster
at age 22 years to extend duration an additional 10 years resulted in a cost
of $77 000 per life-year gained for the delayed strategy compared with
screening only.
Based on the results of the 1-way sensitivity analyses, we conducted
a 2-way sensitivity analyses in which the total cost of the vaccine (assumed
to include the costs for administration, a series of 3 shots, and any boosters
needed to maintain efficacy over the duration modeled) was simultaneously
varied with the duration of vaccine efficacy. These results indicated that
at lower total costs for the vaccine and longer duration, the strategy of
vaccinating all girls (at age 12 years) and delaying the onset of screening
until age 24 years dominated a strategy of screening only beginning at age
18 years (Figure 3A). However, as
the total cost for the vaccine increased, the incremental cost-effectiveness
ratio associated with the delayed strategy increased. The area over which
the delayed strategy dominated screening only increased if the age of vaccination
was increased (until approximately age 15 years) or time costs for screening
and vaccination, as well as utilities for cancer, CIN 1, and CIN 2-3 were
included in the model (Figure 3B).
If vaccination was delayed until a later age (≥16 years) or duration of
vaccine efficacy was shorter than 9 years, the area over which the delayed
strategy dominated decreased or disappeared.
Finally, for our main analysis we assumed that a proportion of HPV types
would be targeted by the vaccine, rather than 1 or 2 specific HPV types. Because
this choice may obscure the impact of a type-specific vaccine, we examined
the impact of a vaccine targeted at HPV-16 only. For this analysis, we assumed
that approximately 25% of CIN 1,36 50% of CIN
2-3, and 50% of cancers2,37 were
attributable to infection with HPV 16. Under base-case assumptions about vaccine
efficacy and duration, an HPV-16 only vaccine reduced CIN 1, CIN 2-3, and
cancer incidence by 7%, 11.4%, and 12.5%, respectively. Larger reductions
were achieved when an HPV 16 vaccine was combined with screening or HPV 16
vaccination was assumed to provide lifelong immunity, suggesting that the
relative cost-effectiveness of a type-specific vaccine will depend on the
differential reductions achieved in CIN, and the impact this will ultimately
have on reductions in cancer.
With the prospect of effective vaccines against high-risk HPV types
becoming commercially available within the next 5 to 10 years,4,38 and
the limitations of trials to address all potential scenarios associated with
a vaccine, we conducted an exploratory analysis to identify potentially cost-effective
methods for adding vaccination to an existing screening program and to identify
factors that would affect this decision. For more than a decade, published
economic analyses of cervical cancer screening have consistently shown that
annual screening results in exceptionally large costs with small gains in
life expectancy compared with less frequent screening.7-10,39-42 The
introduction of more sensitive screening tests has made frequent screening
even less economically attractive.15 This is,
in part, due to the fact that screening is most inefficient in younger women
because the detection of transient lesions is greatest, and screening does
not appear to be as effective against the relatively rare aggressive cancers
that do occur in younger women.7,11,13,14 Our
findings suggest that a vaccine, which reduces the incidence of oncogenic
HPV types during the peak ages of infection (generally the late teens and
early 20s), can be economically attractive, especially if it allows for a
delay in the onset of screening.
The key to overall vaccine effectiveness based on this analysis is adequate
protection during the ages of peak oncogenic HPV incidence. Age of vaccination,
HPV types covered, vaccine efficacy, and duration of efficacy are the specific
components that determine this protection. The need for and cost of booster
vaccines to extend duration have a direct impact on the cost-effectiveness
of the vaccine in general. Because long-term (≥10 years) data on vaccine
duration may not be available at the time of commercial availability, policies
that allow for a delay in the onset of screening beyond the current suggested
upper limit of 21 years19 after vaccination
may not be able to be implemented for some time.
Because of the interaction between vaccine duration and age at vaccination
in terms of overall vaccine effectiveness, research needs to be focused on
the optimal time to offer vaccination, especially because the proportion of
the female population who are vaccinated successfully also has cost-effectiveness
implications. Although vaccinating young girls prior to the onset of sexual
activity may be ideal in terms of an immunologically naive population, it
is currently unclear whether parents will agree to have their children vaccinated
against a sexually transmitted infection. An additional concern highlighted
by our sensitivity analysis is that if women who are vaccinated perceive themselves
to be at low risk for developing cancer and, as a result do not participate
in screening as recommended, gains from vaccination may be offset.
Our analyses also showed that assumptions about the natural history
of HPV infection and response to vaccine, such as the age-specific and lesion-specific
distribution of high-risk types, the impact of treatment of cervical neoplasia
on subsequent risk for neoplasia, the differential impact of a type-specific
vaccine such as HPV 16 on CIN 1 compared with CIN 2-3 and cancer, and assumptions
about women who do not respond to vaccination affect cost-effectiveness conclusions.
In addition, it is unclear whether the vaccine will have an impact on cancers
that occur in younger women, as predicted by the model. It is possible that
the biological characteristics that lead to cancers in younger women are somehow
related to response to the vaccine. If the vaccine is less effective against
those HPV infections that occur in younger women, then we are overestimating
the benefits of the vaccine. At the policy level, all of these parameters
affect the net effectiveness of a vaccine—lower effectiveness makes
a vaccine less attractive from both clinical and economic grounds. Refinement
of models as further data become available will improve predictions of vaccine
impact.
It should also be noted that, even with sensitivity analyses, we cannot
entirely account for uncertainty in our results. For example, some of the
strategies, which are clustered closely together near the efficiency curve
depicted in Figure 2, might be considered
reasonable alternatives if other noneconomic reasons existed for adopting
them. Given the uncertainty in both the probability and cost estimates, it
is also possible that even slightly different base-case estimates for some
probabilities and costs might result in some strategies, which are dominated
in the current base case but that lie close to the efficiency curve, becoming
economically preferred.
We did not model HPV as an infectious disease, largely because of an
almost complete lack of data on the sexual transmission dynamics of HPV. In
addition, because current clinical trials are directed at vaccinating females,
we did not directly consider the impact of vaccinating males. An effective
vaccine, by reducing prevalence, will lead to further decreases in incidence
through reduced transmission. If this is the case, then even partial coverage
by a vaccine could result in even greater decreases in population incidence
and prevalence than our analysis indicates.43
Our use of utilities for cancer and preinvasive lesions in sensitivity
analyses should be interpreted with caution. There is a lack of data on cervical
cancer-specific utilities, including those associated with screening. In addition,
the appropriate method for measuring and including screening-associated utilities
has yet to be determined. Screening using HPV tests or cytologic examinations
can be associated with significant psychological distress as well as morbidity.44,45 Additionally, the psychological and
physical adverse effects that result from cervical cancer treatment are well
documented.46,47 Cost-effectiveness,
as measured by quality-adjusted life expectancy, is quite sensitive to assumptions
about the relative disutility of screening vs cancer, underscoring the need
for studies that can provide appropriate measures for quality-of-life calculations.
Based on our results, the ability to change screening policies efficiently
is dependent on maintaining adequate vaccine efficacy during the ages of peak
oncogenic HPV incidence. Availability of a vaccine will not lead to overnight
changes in screening policy: the majority of older women will not be eligible
for a vaccine, and uncertainty about issues that impact overall effectiveness,
such as vaccine duration and replacement, is unlikely to be resolved prior
to commercial availability. Data on vaccine parameters, such as type-specific
efficacy, duration, and impact on other HPV types will be collected as part
of ongoing trials, as well as in other studies. Because the impact of these
clinical and epidemiological variables on overall vaccine effectiveness is
so dependent on the age at which vaccination is given, research into understanding
the feasibility and acceptability of vaccination at different ages should
be given high priority.
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