Cervical Cancer Prevention Yesterday, Today and Tomorrow

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Cervical Cancer PreventionYesterday, Today and
Tomorrow

• John F. Boggess, M.D.
• Gynecology Oncology
• Lineberger Comprehensive Cancer Center

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Cervical Cancer Facts

• Second leading cause of cancer death worldwide
• Bimodal age distribution
• Risk factors include age, smoking, number of
  sexual partners, STDs (HPV)
• Early stages of disease are not symptomatic

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Incidence United States

• 12,800 new cases per year
• 4,800 annual deaths
• 14.2/100,000 (1973)
• 7.8/100,000 (1994)

CA Cancer J Clin, 1999
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Are Pap Smears Effective?

• Incidence
• 1940 1991
• 32.6 7.9

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Hoskins, Principles and Practices of Gynecologic
Oncology
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Mortality

• 1950-1970 70 Reduction
• 1970-1995 40 Reduction

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Cervical Cancer Mortality

• World Wide 14.7-0.6
• (Mexico-Thailand)
• United States 2.7
• North Carolina
• White 2.3
• Non-White 7.2

Rate per 100,00 population
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Screening Failures

• 50-70 of cancers occur in women who are not
  screened ever or within 5 years
• Among screened women, failures occur due to
• 1. Failure to adequately follow-up screened
  abnormalities (22-63)
• 2. Rapid progression (50 with 3 year interval)
• 3. Abnormalities missed by screening test
  (14-33)
• a. sampling error
• b. detection error

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Strategies for Improving Screening

• Thin layer cytology Thinprep,Autocyte
• Computerized re-screening Papnet
• Algorithm-based AutoPap
• HPV testing Digene II

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HPV Virology
Genus A of Papovaviridae family Non-enveloped DNA
virus Icosohedral capsid Over 70 types based
upon DNA homology Genome divided into three
regions URR, Early genes, Late genes High
oncogenic risk 16, 18, 31 Low oncogenic risk 6,
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Objectives of Universal Screening

• Decrease cervical cancer deaths
• Intervene when conservative measures can effect a
  cure
• Identify women at risk and provide education

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Clinical Dilemma

• Abnormal Paps 4.1 Million

Invasive 0.3
Pre-Invasive 4.4
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Pap/Biopsy Correlation
Biopsy

• Normal LGSIL HGSIL
• ASCUS 45 46 9
• LGSIL 38 47 16
• HGSIL 7 18 75

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Natural History of CIN I

• Regression 60
• Persistence 30
• Progression 10

Ostor, 1993
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Two Sides to the Coin

• Pap smear screening can prevent cervical cancer
  deaths.
• Minimally abnormal Pap smears rarely predict a
  cancer outcome and result in costly work-ups.

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NCI Progress Review Group

• Identify precursor lesions
• markers of risk
• molecular disease classifications
• prognostic indicators
• targets for prevention and treatment
• Develop effective HPV vaccines
• Eliminate disparities among differing populations

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How UNC is positioned to be a leader in this area

• Biomarkers
• Population Genetic Screening
• Social Intervention and Education
• Clinical Trials
• Vaccine
• Novel Medical Therapies

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Conclusions

• Screening is effective
• Not screening is not effective and is the major
  cause of cancer death in United States
• All systems based upon the Pap smear have a low
  sensitivity and rely on repeat screening
• New technologies improve sensitivity at the
  expense of cost and specificity

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Future Emphasis

• Vaccination
• Defining what diagnostic and screening methods to
  use and at what interval
• Targeted screening based upon risk (social and
  biomarkers)
• Balancing cost with technology