MS&E 220 Project Yuan Xiang Chew, Elizabeth A Hastings,
Morris Jinhui Zhang Probabilistic Analysis of Cervical Cancer
Screening and Vaccination
Slide 2
Executive summary Using a dynamic model with statistics from
literature, we modeled the development of cervical cancer in women
between the age 18 and 65. Our results show that a combination of
screening at an interval of 5 years with vaccination using the drug
Gardasil would lead to cost savings in Pap smear screening while
achieving a lower lifetime probability of cancer (0.807%) as
compared to the lifetime probability from biennial screening as
recommended by the National Cancer Institute (0.812%). This is a
conservative recommendation given that the vaccine effectiveness
that we used (50%) is the lower limit of the reported statistics.
Performing a sensitivity analysis, increasing the vaccine
effectiveness will not change our recommendation.
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Background Cervical Cancer: Cervical cancer is the second most
common type of cancer in women. Nearly all cervical cancers are
caused by certain strains of the human papillomavirus (HPV). Before
becoming cancerous, precursor legions called cervical
intraepithelial neoplasia (CIN) form. Traditional approaches to
reducing the prevalence of cervical cancer have focused on early
detection and treatment. If detected at pre-cancerous stages a
large proportion, approximately 85% to 98%, of the legions can be
treated and prevented from becoming cancerous. Prevention and
Treatment of Cervical Cancer: The most widely adopted screening
method to detect precursor legions is the Pap smear. The American
Cancer Society recommends that women between the ages of
approximately 18 and 65 receive Pap smears biennially. The
mortality rate from cervical cancer has dropped by 70% overall
since the introduction of Pap smears. The sensitivity of Pap smears
is not accurately known, and estimates range from 51% to 80%. A
more recent method to reduce the occurrence of and mortality from
cervical cancer is through vaccination. The Gardasil vaccine was
approved by the FDA and introduced in the U.S. in 2006. The vaccine
is recommended only for women under 26 years old, and it is
estimated that it prevents 96% to 100% of the two HPV strains that
lead to 70% to 80% of cervical cancers. The duration of the
vaccines effectiveness, however, is unclear other than that is it
greater than five years. The American Cancer Society recommends
that women who receive the vaccine continue biennial
screening.
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Objectives Understand how changing the frequency of screening
changes the probability that a woman will develop or die from
cervical cancer in her lifetime. Recommend screening routines that
are optimal in promoting health while being cost effective.
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Model
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Key assumptions in model Cervical cancer risk exists from age
15 to 60. Progression from Well to CIN stages is governed by a
probability density function of age (statistically fitted).
Transition probabilities from CIN to Cancer and to Death are given
by literature values. Screening and diagnosis lowers the transition
probabilities as treatment is dispensed. If a patient survives 5
year of Cancer, she returns to the state of Well.
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Effects of Vaccination The combined lifetime probability is
much lower for the case of using the vaccine with screening than
just screening alone.
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Effects of Screening Frequency (No vaccination) This figure
shows that the probability of developing cancer decreases as
screening frequency increases. With scenarios where screening
occurs every 2 years to every 5 years, the PMF is wavy because if a
legion is detected through screening, the likelihood of going back
to the well state increases as the patient in theory undergoes
preventive treatment. Therefore, the probability of developing
cancer is lowest in the year following screening.
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Effects of Screening Frequency (No vaccination) Figure 4 shows
that the cumulative lifetime probability of developing cancer is
4.473% where there is no screening, compared to 0.574% with annual
screening. Decreasing the frequency of screening from every year to
every two years increases the probability from 0.574% to 0.756%.
The probability increases by an additional 0.1% to 0.2% for further
decreases in screening frequency. All screening scenarios, even
every five years, leads to a significantly lower probability of
developing cancer as opposed to no screening. This figure shows
that the cumulative lifetime probability of developing cancer is
4.473% where there is no screening, compared to 0.574% with annual
screening. Decreasing the frequency of screening from every year to
every two years increases the probability from 0.574% to 0.756%.
The probability increases by an additional 0.1% to 0.2% for further
decreases in screening frequency. All screening scenarios, even
every five years, leads to a significantly lower probability of
developing cancer as opposed to no screening.
Slide 10
Combined Effects of Screening and Vaccination This graph shows
that the vaccine has a significant effect with zero screening, and
combining the vaccine with screening every five years results in a
lower probability of developing cancer than screening each year
without the vaccine. It can also be seen that with the vaccine,
screening every five years will result in approximately the same
probability as screening yearly without vaccine.
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Cost Effective Recommendation Achieve same risk with lower cost
by screening every 5 years, with vaccination Traditional biennial
screening without vaccine
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Sensitivity Analysis For the patient to switch to screening
once in 3 years and maintain the same combined probability of death
and cancer as the recommended case, the screening effectiveness
would have to reach 99.7%, which is unrealistic today. If the
patient switches to screening every year, the screening
effectiveness can fall to 50.3% before the combined probability
will fall below that of the recommended case.
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Conclusion Recommendations To maintain current risk of cervical
cancer while reducing cost: Screen every 5 years Use vaccine To
decrease risk of cervical cancer below current risk at lowest cost:
Screen more often that every 5 years Use vaccine If vaccine is not
used, base case biennial screening recommended (in line with
National Cancer Institutes recommendation) Further Study Compare
the lives saved and cost of preventing cervical cancer to the lives
saved and cost for lowering the risk of other diseases. If lowering
the risk of cervical cancer below its current rate compares
favorably in terms of cost-benefit with other health investments,
support increased vaccination and screening funding. Consider use
of vaccine in developing countries where access to screening is
limited.