A Cervical Cancer Decision Model to Inform Recommendations About Preventive Services

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A Cervical Cancer Decision Model to Inform
Recommendations About Preventive Services
Perspective of the Decision ModelerShalini
Kulasingam, PhDDuke UniversityDurham, NC
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The Natural History of Cervical Cancer
Clearance
HPV infected Cervix
Regression
Invasion
Normal Cervix
Pre-cancer CIN 3
Cancer
Infection
Progression
Regression
Progression
Self-limited Infection (CIN 1, CIN 2?)
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Why a Decision Model for Cervical Cancer?

• Natural history
• New screening tests
• HPV tests
• Cervical cytology tests
• Vaccination
• Guidelines
• What age to begin screening
• What age to end screening
• Screening frequency

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An RCT for Every Combination is Impossible

• 3 screening tests
• 15 different ages to start screening
• 8 different ages to end screening
• 1 big headache insufficient funds

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What is a Model?
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State Transition Model
Screening affects transitions for CIN 1, CIN 2-3
and cancer (Stage I)
NmlNormal
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The Duke Cervical Cancer Model

• Markov state transition model of HPV, cervical
  pre-cancer and cancer
• Can account for impact of screening and
  vaccination
• Original model developed for 1999 AHRQ evidence
  report on new cervical cancer screening
  technologies by Evan Myers, MD, MPH (Professor,
  Duke University)
• Validated by comparing outcomes to
• Reported outcomes (e.g., SEER)
• Outcomes predicted by other independently
  developed models
• Used by a number of different academic groups and
  by government agencies and pharmaceutical
  companies
• Limitations
• Reflects clinical practice and includes CIN 1 as
  a state
• Scientifically moving toward defining CIN 3 as
  the only true pre-cancer state
• Data are grouped into age categories that may be
  blunt to one-year age differences

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How Do We Use the Model to Calculate an Outcome?

• Life-years gained
• With screening and treatment, more women
• survive for a longer time
• Model calculates average life-expectancy for the
  cohort with and without screening and treatment
• LYG is difference between these two
• Colposcopies Task Force measure of burden of
  screening
• Cost traditional measure of resources used

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Current Recommendations (2003)

• Direct evidence to determine the optimal starting
  and stopping age and interval for screening is
  limited. Indirect evidence suggests most of the
  benefit can be obtained by beginning screening
  within 3 years of onset of sexual activity or age
  21 (whichever comes first) and screening at least
  every 3 years
• The USPSTF recommends against routinely screening
  women older than age 65 for cervical cancer if
  they have had adequate recent screening with
  normal Pap smears and are not otherwise at high
  risk for cervical cancer
• The USPSTF concludes that the evidence is
  insufficient to recommend for or against the
  routine use of new technologies to screen for
  cervical cancer

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Questions posed by USPSTF

• Age to begin cervical cancer screening
• Age to end cervical cancer screening
• Role of HPV tests in primary screening and triage
  of abnormal cytology results
• Role of liquid-based cytology

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Communicating with the TF.
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Issues in Answering the TF Questions

• Evidence Report for Screening Tests
• Oregon EPC
• Use the data from this report for the model
• Need to coordinate so that the findings are
  consistent
• Short time frame
• Original time frame of 3 months
• The oh you have a model syndrome
• Change in model structure
• Change in questions and output requested
• Keeping up with an onslaught of HPV and cervical
  cancer studies

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Results Age to Begin Screening
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Results Age to End Screening
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Results Age to End Screening
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Results HPV DNA Tests
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Results Liquid vs. Conventional Cytology
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Summary of Model Results

• Age 21, screening q3 depends on measure used
• Little benefit to screening well screened women
  after age 65
• HPV testing for women with ASCUS confirmed role
  in primary screening remains unclear
• Preference for screening using conventional or
  LBC depends on classification of CIN 1

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Shortcomings of the Current Approach

• What outcome?
• Colposcopies similar to colonoscopies?
• How do current guidelines affect findings?
• ASCCP guidelines for Age 21
• How do we compare our results with others?
• Cost per life-year

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Shortcomings (?) of the Current Model

• Natural history
• Role of CIN 1
• Vaccination
• Need to change/construct new model(s)

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Acknowledgements

• Laura Havrilesky, MD, Duke University
• Evan Myers, MD, Duke University
• Julian Irvine, Duke University
• Task Force esp. George Sawaya, MD and Diana
  Petitti MD, PhD
• AHRQ Tracy Wolff, MD, Tess Miller DrPh and Mary
  Barton, MD CDC Mona Saraiya, MD, MPH
• Funded by the United States Centers for Disease
  Control and Prevention and the Agency for
  Healthcare Research and Quality
• Shalini Kulasingam is supported by NCI grant
  K07-CA113773