Cervical Cancer Screening

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Cervical Cancer Screening

• Alternatives for the Developing World
• Edith H. Harte MD October 22, 2003

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Focus of PresentationCervical Cancer Screening

• Review incidence, etiology, and natural history
  of cervical cancer
• Discuss cervical cancer screening
• Limitations of PAP screening in low resource
  areas
• Alternatives to PAP, particularly Visual
  Inspection with 5 acidic acid (VIA)
• Discuss potential screening program for Santa
  Lucia, Intibuca in Honduras

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Cervical Cancer IncidenceKey Facts

• Incidence in USA markedly decreased since 1941
  when Papanicolou screening started
• Organized cytology programs have reduced the
  incidence of and mortality from cervical CA in
  developed world
• Burden of disease highest in developing nations
  where populations are unscreened

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Cervical Cancer Incidence

• USA
• 3rd most common malignancy of female lower
  genital tract
• 12,000 new cases 4,600 deaths annually
• 6 cases/100,000
• Honduras
• Most common female cancer
• 40 cases/100,000

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Cervical Cancer

• Most cases found in women never screened or
  not screened for more than 5 years.
• High rates in the developing world directly
  related to the lack of screening programs
• As in the USA introduction of screening programs
  in other countries has decreased the incidence
  of invasive disease

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Age Adjusted Death Rate for Cervical Cancer in
US
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Characteristics of Cervical Cancer

• Long time period of pre-invasive state
• May take 10 yrs or more to progress
• Begins as mild dysplasia
• Many regress spontaneously( at least 50)
• Most are squamous cell types (80)
• Local spread
• Lymphatic spread

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Stages of Cervical Cancer

• I. Confined to cervix
• II. Tumor extends beyond uterus, but not to
  pelvic side wall or lower 1/3 of vagina
• III. Tumor extends to pelvic side walls or lower
  1/3 of vagina
• IV. Spread to bowel or bladder or distant
  metastasis

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Risk Factors for Cervical Cancer

• Multiparity
• Early intercourse
• Early childbearing
• Multiple and high risk sexual partners
• Sexually transmitted infections
• HPV infection
• Low socioeconomic status
• Previous dysplasia

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Other Risk Factors

• Immunosuppression
• Cigarette smoking
• DES Exposure
• OCPs

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Role of HPV

• 95 squamous cervical cancers may have HPV DNA
• HPV infects reproducing cells of basal layer
• If HPV integrates into cells DNA
• May lead to cell transformation
• May result in high grade SIL or CA
• Many types exist 16,18,3145 high risk

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Rational for Cervical Cancer Screening

• To detect pre-invasive disease
• Cervical cancer has long pre-invasive state
  allowing for detection in the pre-malignant
  state
• Can potentially prevent progression to invasive
  cancer

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OBJECT

• To find a screening test that will differentiate
  between a healthy and a diseased cervix
• Pap testing has been the standard in USA
• VIA has compared favorably with cytology in
  several studies done in China, India, and Africa

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How to Evaluate a Screening Test

• Sensitivity proportion of truly diseased people
  in a study population that are correctly
  identified as having the disease by the test.
• Specificity proportion of non diseased persons
  correctly identified as not having the disease.
• Positive Predictive Value Proportion of people
  with a positive test who have the disease

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Pap Screening Limitations

• Relatively poor sensitivity (51-66)
• Imperfect collection methods
• Imperfect transfer of cells to slide or bottle
• Lesions that may not exfoliate
• Cytologist error

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Pap Screening

• Problematic in low resource areas
• Lack of organized screening and follow-up
  programs
• Lack of technology and availability
• Lack of resources for reading cytology
• Lack of colposcopy resources for abnormal Paps
• Lack of follow-up procedures

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Alternative Strategies for Detecting Cervical
Cancer

• Visual Inspection
• Visual Inspection with Acetic Acid (VIA)
• Cervicography
• Speculoscopy- VIA with chemiluminescent light
  source
• HPV DNA testing

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Visual Inspection with Acetic Acid (VIA)

• Unmagnified visualization of cervix after
  application of 5 acetic acid
• Acetic acid application has a long history of
  use during colposcopy to locate abnormal areas.
• Aceto white changes after application may
  indicate
• Abnormal transformation zone
• Areas of increased cellular density with
  increased abnormal nuclei and DNA content

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Precedents for VIA

• Studies done in India , Africa and China
  indicate that VIA compares favorably with pap
  screening in terms of sensitivity and specificity

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VIA

• Meets criteria for a good screening test
• Compares favorably with pap screening
• May be more sensitive (66-96)
• Is less specific (more false positives)
• Has the potential to improve screening,
  follow-up and treatment rates in low resource
  settings

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Biology of the Transformation zone

• External cervix covered with squamous epithelium
  looks smooth
• Endocervical canal populated by columnar
  epithelium cells- looks red
• Squamocolumnar junction border between these
  cell types
• Its location changes according to age and
  hormonal status
• Migrates to portia in reproductive age women

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Transformation Zone

• Area between the old and new squamocolumnar
  junctions where squamous metaplasia occurs
• Area where most (95) cervical dysplasias and
  cancers occur

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Squamocolumnar Junction
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Normal Squamocolumnar Junction

• Squamous epithelium is smooth and pink
• Columnar epithelium appears red
• There are no aceto white changes

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Squamocolumnar Junction with Squamous Metaplasia

• Normal Junction
• Minimal white ring at junction
• Squamous Meta-
• plasia normal variant

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VIA Advantages

• Quick, easy, and non-invasive
• Requires minimal equipment
• Results are immediately available
• Good sensitivity-especially for higher
• grade lesions
• Few false negatives

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VIA Disadvantages

• Lower specificity (more false positives)
• Increased costs for referrals to colposcopy
• Potential of unnecessary biopsies
• Follow up of abnormals that dont get
  colposcopies

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How to Screen GYN Patients

• Take gyn history focusing on risk factors and
  symptoms
• Examine patient starting at top
• Perform speculum exam
• Carefully inspect vulva ,vagina cervix
• Do bimanual exam
• Perform VIA

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Gyn History

• Cycles Lmp reg irreg length flow
• Abnormal bleeding
• Intermenstrual
• postcoital bleeding
• Abnormal vaginal discharge
• Pelvic or back pain
• Assess risk factors

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Physical Exam

• General appearance evidence wasting
• Lymph nodes supraclavicular
• Abdomen mass
• Pelvic
• cervix gross lesions, elongated or unusual
  shape, tactile bleeding, ulcerations
• vagina presence of lesions
• Bimanual very hard cervix, palpable mass
• Rectovaginal mass may extend laterally

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How to Perform VIA

• Do speculum exam
• Wipe away secretions
• Apply 5 acetic acid
• Wait 3 minutes
• Look for white areas
• Record results
• Biopsy any opaque white areas
• Biopsy obvious lesions

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Normal VIA

• Normal appearing cervix
• No aceto-white changes seen
• Minimal translucent or very pale white
  epithelium at SCJ is normal and may indicate
  squamous metaplasia
• Record result
• No further testing needed

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Normal VIA

• Normal SCJ
• No white areas

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Abnormal VIA

• Opaque white epithelium results after acetic
  acid application
• Record result
• Biopsy whitest area
• Biopsy any gross lesion
• Biopsy and do ecc in elongated or abnormally
  shaped cervices

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Cervical Dysplasia

• Opaque white epithelium
• Occurs at SCJ

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Cervical Dysplasia

• Aceto white epithelium surrounds cervical os
• Internal margins of more densely white
• epithelium

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Cervical Dysplasia

• Diffuse aceta white changes
• Most prominent at 6 10 oclock

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Severe Dysplasia

• Marked acetowhite epithelium
• Abnormal raised contour

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Carcinoma In Situ
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Features of early cancer lesions

• Oyster shell white
• Rolled edges
• Abnormal vessels
• Friable
• Uneven surface

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Invasive Cancer

• Raised lesion
• Rolled edges
• Raised white epithelium
• Abnormal vessels
• Important to biopsy this

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What Needs to be Done in Santa Lucia

• Develop screening program
• Develop recording system
• Find reliable pathology lab
• Develop follow-up systems
• Untreated positives
• Post treatment patients
• Develop system for referral for treatment
• Teach local physicians and nurses to perform
  screening

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What Have We Done this Week?

• Screened 80 women ( 7 days) for breast and pelvic
  cancers
• 70 had normal VIA
• 10 had abnormal VIA and had cervical biopsies
• 3 had cervical polyps removed
• 2 required endometrial biopsies for abnormal or
  postmenopausal bleeding
• 1 case of advanced invasive cervical cancer was
  found
• Developed registration and recording system
• Found a Pathology Lab