Shoulder to Shoulder: Cervical Cancer Screening

Cervical Cancer Screening Alternatives for the Developing World Edith H. Harte MD October 22, 2003

Focus of Presentation: Cervical 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

Cervical Cancer Incidence Key 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

Cervical Cancer Incidence
USA
3 rd 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

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

Age – Adjusted Death Rate for Cervical Cancer in US

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

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

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

Other Risk Factors
Immunosuppression
Cigarette smoking
DES Exposure
OCPs

Role of HPV
95% squamous cervical cancers may have HPV DNA
HPV infects reproducing cells of basal layer
If HPV integrates into cell’s DNA
May lead to cell transformation
May result in high grade SIL or CA
Many types exist; 16,18,31&45 high risk

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

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

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

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

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

Alternative Strategies for Detecting Cervical Cancer
Visual Inspection
Visual Inspection with Acetic Acid (VIA)
Cervicography
Speculoscopy- VIA with chemiluminescent light source
HPV DNA testing

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

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

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

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

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

Squamocolumnar Junction

Normal Squamocolumnar Junction
Squamous epithelium is smooth and pink
Columnar epithelium appears red
There are no aceto white changes

Squamocolumnar Junction with Squamous Metaplasia
Normal Junction
Minimal white ring at junction
Squamous Meta-
plasia –normal variant

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

VIA Disadvantages
Lower specificity (more false positives)
Increased costs for referrals to colposcopy
Potential of unnecessary biopsies
Follow up of abnormals that don’t get colposcopies

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

Gyn History
Cycles : Lmp; reg; irreg; length; flow
Abnormal bleeding;
Intermenstrual;
postcoital bleeding
Abnormal vaginal discharge
Pelvic or back pain
Assess risk factors

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

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

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

Normal VIA
Normal SCJ
No white areas

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

Cervical Dysplasia
Opaque white epithelium
Occurs at SCJ

Cervical Dysplasia
Aceto white epithelium surrounds cervical os
Internal margins of more densely white
epithelium

Cervical Dysplasia
Diffuse aceta white changes
Most prominent at 6& 10 o’clock

Severe Dysplasia
Marked acetowhite epithelium
Abnormal raised contour

Carcinoma In Situ

Features of early cancer lesions
Oyster shell white
Rolled edges
Abnormal vessels
Friable
Uneven surface

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

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

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

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Shoulder to Shoulder: Cervical Cancer Screening

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Shoulder to Shoulder: Cervical Cancer Screening Presentation Transcript