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 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

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

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