Cervical Cancer: Natural History, Screening and Prevention

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Cervical Cancer Natural History, Screening and
Prevention

• Diane Solomon, MD
• Division of Cancer Prevention

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Cervical Cancer Overview

• Etiology of cervical cancer
• Mortality statistics
• Screening
• Introduction of new technologies
• Vaccine development

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Transformation Zone

•  A. Normal B. Low grade
  lesion

C. Precancer D. Cancer
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HPV Cervical Cancer

• HPV infection
• over 100 types of HPV
• approximately 30 types involve genital tract
• approximately 15 types associated with cervical
  cancer most common 16 and 18,
• Low risk HPV types
• Genital warts most common HPV types 6 11
• many LR types subclinical 53 61

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Risk FactorsCervical Cancer

• HPV is a key factor for cervical cancer
• Primarily sexually transmitted
• BUT, HPV infection is common and cervical CA is
  not therefore, other factors are involved
• Immunosuppression
• Smoking
• Lack of screening is an important risk factor

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10-Year CI of CIN3 Among Oncogenic HPV/-
Portland
Castle et al., JNCI, 2002
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Cervical Cancer Overview

• Etiology of cervical cancer
• Mortality statistics
• Screening
• Introduction of new technologies
• Vaccine development

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Cervical Cancer Mortality

• Worldwide, it is the second most common cancer
  among women in many developing countries, it is
  the 1 killer of women
• In the US, 14,000 women develop cervical cancer
  and 4,500 die of the disease each year in the US
• Peak incidence 40 - 45 years
• one quarter of cases in women gt60

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Cervical Cancer Overview

• Etiology of cervical cancer
• Mortality statistics
• Screening
• Introduction of new technologies
• Vaccine development

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Screening Cervical Cancer

• Papanicolaou Smear
• Largely responsible for the 70 decrease in
  cervical cancer mortality over the last 50 years
• One of the most cost effective screening tests
• Prevents development of cancer

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Cervical Cancer Screening

• Cervix can be seen and sampled
• Screening tests available
• Precancer stage which can be found and treated
  BEFORE cancer even develops

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Identifying and Validating Biomarkers in Cervical
Pathogenesis
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New Technologies

• Cytology
• Liquid based cytology
• Computer assisted imaging
• HPV testing
• HPV Vaccines

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Cervical Lesions Pyramid of Diagnoses
CA 15,000
HSIL 300,000
LSIL 1,200,000
ASCUS 2,000,000
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HPV testing Triage and Screening

• Triage
• HPV testing following ASC-US cytology
• All ages
• Primary Screening
• Concurrent cytology and HPV testing
• ONLY for women gt 30

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ACOG Screening GuidelinesACOG Practice Bulletin
45 August 2003

• When to start?
• Start screening approximately 3 years after the
  onset of vaginal intercourse or no later than
  age 21
• For women lt 30 annual screening
• (ACS annual if conventional smears, or every two
  years using liquid-based cytology)

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ACOG Screening GuidelinesACOG Practice Bulletin
45 August 2003

• Post Hysterectomy
• If done for benign reasons and no history of
  previous lesions, then may discontinue routine
  testing
• If history of CIN 2 or CIN 3, then screen
  annually until three negative tests, then may
  discontinue
• When to Discontinue
• Age 65-70 if have had previous negative Pap tests
  over the past 10 years

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ACOG Screening GuidelinesACOG Practice Bulletin
45 August 2003

• For women gt 30
• As an option, may combine HPV testing and
  cytology for screening if neg/neg then extend
  interval to every 3 years
• Increases sensitivity for CIN3
• Why limit to women gt 30?
• Why screen only every 3 years?

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HPV Prevalence and Cervical Cancer Incidence by
Age
Cancer incidence per 100,000
HPV Prevalence ()
Age (Years)
1. Sellors et al. CMAJ. 2000163503. 2. Ries et
al. Surveillance, Epidemiology and End Results
(SEER) Cancer Stats NCI, 1973-1997. 2000.
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Identifying and Validating Biomarkers in Cervical
Pathogenesis
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Cervical Cancer Overview

• Etiology of cervical cancer
• Mortality statistics
• Screening
• Introduction of new technologies
• Vaccine development

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HPV 16 and HPV 18

• Together cause 60-70 of squamous cell cervical
  cancers and 80 of cervical adenocarcinoma
• Common in CIN3/cancers and in the general
  population
• HPV16 has increased likelihood of persistence
• Is there a role for type-specific HPV testing in
  cervical cancer screening

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Prophylactic HPV Vaccines

• Merck quadrivalent types 6-11-16-18
• GSK types 16-18
• VLP format
• Effective in preventing incident cervical
  infections with HPV 16/18 and associated lesions
• Require multiple injections and is expensive
• Questions remain regarding duration of
  protection, cross protection, efficacy vs
  established infections, age to vaccinate, etc.

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Prophylactic HPV Vaccines

• Will still need screening
• Women previously infected
• Other oncogenic HPVs
• But screening may be very different .

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Cervical Screening

• To reduce cervical cancer mortality, we need to
  reach women who are under-screened -- older,
  minority, rural, poor -- with any current
  technologies.
• To make screening more efficient we need to
  identify new markers of high grade disease or
  consider new screening strategies with currently
  available technologies.
• No single test or combination of tests is 100
  effective. Need to balance increased sensitivity
  with resulting unnecessary testing and follow up.