Shoulder to Shoulder: Cervical Cancer Screening


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Shoulder to Shoulder: Cervical Cancer Screening

  1. 1. Cervical Cancer Screening Alternatives for the Developing World Edith H. Harte MD October 22, 2003
  2. 2. Focus of Presentation: Cervical Cancer Screening <ul><li>Review incidence, etiology, and natural history of cervical cancer </li></ul><ul><li>Discuss cervical cancer screening </li></ul><ul><ul><li>Limitations of PAP screening in low resource areas </li></ul></ul><ul><ul><li>Alternatives to PAP, particularly Visual Inspection with 5% acidic acid (VIA) </li></ul></ul><ul><li>Discuss potential screening program for Santa Lucia, Intibuca in Honduras </li></ul>
  3. 3. Cervical Cancer Incidence Key Facts <ul><li>Incidence in USA markedly decreased since 1941 when Papanicolou screening started </li></ul><ul><li>Organized cytology programs have reduced the incidence of and mortality from cervical CA in developed world </li></ul><ul><li>Burden of disease highest in developing nations where populations are unscreened </li></ul>
  4. 4. Cervical Cancer Incidence <ul><li>USA </li></ul><ul><ul><li>3 rd most common malignancy of female lower genital tract </li></ul></ul><ul><ul><li>12,000 new cases; 4,600 deaths annually </li></ul></ul><ul><ul><li>6 cases/100,000 </li></ul></ul><ul><li>Honduras </li></ul><ul><ul><li>Most common female cancer </li></ul></ul><ul><ul><li>40 cases/100,000 </li></ul></ul>
  5. 5. Cervical Cancer <ul><li>Most cases found in women never screened or not screened for more than 5 years. </li></ul><ul><li>High rates in the developing world directly related to the lack of screening programs </li></ul><ul><li>As in the USA introduction of screening programs in other countries has decreased the incidence of invasive disease </li></ul>
  6. 6. Age – Adjusted Death Rate for Cervical Cancer in US
  7. 7. Characteristics of Cervical Cancer <ul><li>Long time period of pre-invasive state </li></ul><ul><ul><li>May take 10 yrs or more to progress </li></ul></ul><ul><ul><li>Begins as mild dysplasia </li></ul></ul><ul><ul><li>Many regress spontaneously( at least 50%) </li></ul></ul><ul><li>Most are squamous cell types (80%) </li></ul><ul><ul><li>Local spread </li></ul></ul><ul><ul><li>Lymphatic spread </li></ul></ul>
  8. 8. Stages of Cervical Cancer <ul><li>I. Confined to cervix </li></ul><ul><li>II. Tumor extends beyond uterus, but not to pelvic side wall or lower 1/3 of vagina </li></ul><ul><li>III. Tumor extends to pelvic side walls or lower 1/3 of vagina </li></ul><ul><li>IV. Spread to bowel or bladder or distant metastasis </li></ul>
  9. 9. Risk Factors for Cervical Cancer <ul><li>Multiparity </li></ul><ul><li>Early intercourse </li></ul><ul><li>Early childbearing </li></ul><ul><li>Multiple and high risk sexual partners </li></ul><ul><li>Sexually transmitted infections </li></ul><ul><li>HPV infection </li></ul><ul><li>Low socioeconomic status </li></ul><ul><li>Previous dysplasia </li></ul>
  10. 10. Other Risk Factors <ul><li>Immunosuppression </li></ul><ul><li>Cigarette smoking </li></ul><ul><li>DES Exposure </li></ul><ul><li>OCPs </li></ul>
  11. 11. Role of HPV <ul><li>95% squamous cervical cancers may have HPV DNA </li></ul><ul><li>HPV infects reproducing cells of basal layer </li></ul><ul><li>If HPV integrates into cell’s DNA </li></ul><ul><ul><li>May lead to cell transformation </li></ul></ul><ul><ul><li>May result in high grade SIL or CA </li></ul></ul><ul><li>Many types exist; 16,18,31&45 high risk </li></ul>
  12. 12. Rational for Cervical Cancer Screening <ul><li>To detect pre-invasive disease </li></ul><ul><li>Cervical cancer has long pre-invasive state allowing for detection in the pre-malignant state </li></ul><ul><li>Can potentially prevent progression to invasive cancer </li></ul>
  13. 13. OBJECT <ul><li>To find a screening test that will differentiate between a healthy and a diseased cervix </li></ul><ul><li>Pap testing has been the standard in USA </li></ul><ul><li>VIA has compared favorably with cytology in several studies done in China, India, and Africa </li></ul>
  14. 14. How to Evaluate a Screening Test <ul><li>Sensitivity: proportion of truly diseased people in a study population that are correctly identified as having the disease by the test. </li></ul><ul><li>Specificity: proportion of non diseased persons correctly identified as not having the disease. </li></ul><ul><li>Positive Predictive Value: Proportion of people with a positive test who have the disease </li></ul>
  15. 15. Pap Screening Limitations <ul><li>Relatively poor sensitivity (51-66%) </li></ul><ul><li>Imperfect collection methods </li></ul><ul><li>Imperfect transfer of cells to slide or bottle </li></ul><ul><li>Lesions that may not exfoliate </li></ul><ul><li>Cytologist error </li></ul>
  16. 16. Pap Screening <ul><li>Problematic in low resource areas </li></ul><ul><ul><li>Lack of organized screening and follow-up programs </li></ul></ul><ul><ul><li>Lack of technology and availability </li></ul></ul><ul><ul><li>Lack of resources for reading cytology </li></ul></ul><ul><ul><li>Lack of colposcopy resources for abnormal Paps </li></ul></ul><ul><ul><li>Lack of follow-up procedures </li></ul></ul>
  17. 17. Alternative Strategies for Detecting Cervical Cancer <ul><li>Visual Inspection </li></ul><ul><li>Visual Inspection with Acetic Acid (VIA) </li></ul><ul><li>Cervicography </li></ul><ul><li>Speculoscopy- VIA with chemiluminescent light source </li></ul><ul><li>HPV DNA testing </li></ul>
  18. 18. Visual Inspection with Acetic Acid (VIA) <ul><li>Unmagnified visualization of cervix after application of 5% acetic acid </li></ul><ul><li>Acetic acid application has a long history of use during colposcopy to locate abnormal areas. </li></ul><ul><li>Aceto white changes after application may indicate </li></ul><ul><ul><li>Abnormal transformation zone </li></ul></ul><ul><ul><li>Areas of increased cellular density with increased abnormal nuclei and DNA content </li></ul></ul>
  19. 19. Precedents for VIA <ul><li>Studies done in India , Africa and China indicate that VIA compares favorably with pap screening in terms of sensitivity and specificity </li></ul>
  20. 20. VIA <ul><li>Meets criteria for a good screening test </li></ul><ul><li>Compares favorably with pap screening </li></ul><ul><ul><li>May be more sensitive (66-96%) </li></ul></ul><ul><ul><li>Is less specific (more false positives) </li></ul></ul><ul><li>Has the potential to improve screening, follow-up and treatment rates in low resource settings </li></ul>
  21. 21. Biology of the Transformation zone <ul><li>External cervix covered with squamous epithelium – looks smooth </li></ul><ul><li>Endocervical canal populated by columnar epithelium cells- looks red </li></ul><ul><li>Squamocolumnar junction: border between these cell types </li></ul><ul><ul><li>Its location changes according to age and hormonal status </li></ul></ul><ul><ul><li>Migrates to portia in reproductive age women </li></ul></ul>
  22. 22. Transformation Zone <ul><li>Area between the old and new squamocolumnar junctions where squamous metaplasia occurs </li></ul><ul><li>Area where most (95%) cervical dysplasias and cancers occur </li></ul>
  23. 23. Squamocolumnar Junction
  24. 24. Normal Squamocolumnar Junction <ul><li>Squamous epithelium is smooth and pink </li></ul><ul><li>Columnar epithelium appears red </li></ul><ul><li>There are no aceto white changes </li></ul>
  25. 25. Squamocolumnar Junction with Squamous Metaplasia <ul><li>Normal Junction </li></ul><ul><li>Minimal white ring at junction </li></ul><ul><li>Squamous Meta- </li></ul><ul><li>plasia –normal variant </li></ul><ul><li> </li></ul>
  26. 26. VIA Advantages <ul><li>Quick, easy, and non-invasive </li></ul><ul><li>Requires minimal equipment </li></ul><ul><li>Results are immediately available </li></ul><ul><li>Good sensitivity-especially for higher </li></ul><ul><li>grade lesions </li></ul><ul><li>Few false negatives </li></ul>
  27. 27. VIA Disadvantages <ul><li>Lower specificity (more false positives) </li></ul><ul><li>Increased costs for referrals to colposcopy </li></ul><ul><li>Potential of unnecessary biopsies </li></ul><ul><li>Follow up of abnormals that don’t get colposcopies </li></ul>
  28. 28. How to Screen GYN Patients <ul><li>Take gyn history focusing on risk factors and symptoms </li></ul><ul><li>Examine patient starting at top </li></ul><ul><li>Perform speculum exam </li></ul><ul><li>Carefully inspect vulva ,vagina & cervix </li></ul><ul><li>Do bimanual exam </li></ul><ul><li>Perform VIA </li></ul>
  29. 29. Gyn History <ul><li>Cycles : Lmp; reg; irreg; length; flow </li></ul><ul><li>Abnormal bleeding; </li></ul><ul><ul><li>Intermenstrual; </li></ul></ul><ul><ul><li>postcoital bleeding </li></ul></ul><ul><li>Abnormal vaginal discharge </li></ul><ul><li>Pelvic or back pain </li></ul><ul><li>Assess risk factors </li></ul>
  30. 30. Physical Exam <ul><li>General appearance; evidence wasting </li></ul><ul><li>Lymph nodes; supraclavicular </li></ul><ul><li>Abdomen; mass </li></ul><ul><li>Pelvic </li></ul><ul><ul><li>cervix: gross lesions, elongated or unusual shape, tactile bleeding, ulcerations </li></ul></ul><ul><ul><li>vagina: presence of lesions </li></ul></ul><ul><li>Bimanual: very hard cervix, palpable mass </li></ul><ul><li>Rectovaginal: mass may extend laterally </li></ul>
  31. 31. How to Perform VIA <ul><li>Do speculum exam </li></ul><ul><li>Wipe away secretions </li></ul><ul><li>Apply 5% acetic acid </li></ul><ul><li>Wait 3 minutes </li></ul><ul><li>Look for white areas </li></ul><ul><li>Record results </li></ul><ul><li>Biopsy any opaque white areas </li></ul><ul><li>Biopsy obvious lesions </li></ul>
  32. 32. Normal VIA <ul><li>Normal appearing cervix </li></ul><ul><li>No aceto-white changes seen </li></ul><ul><li>Minimal translucent or very pale white epithelium at SCJ is normal and may indicate squamous metaplasia </li></ul><ul><li>Record result </li></ul><ul><li>No further testing needed </li></ul>
  33. 33. Normal VIA <ul><li>Normal SCJ </li></ul><ul><li>No white areas </li></ul>
  34. 34. Abnormal VIA <ul><li>Opaque white epithelium results after acetic acid application </li></ul><ul><li>Record result </li></ul><ul><li>Biopsy whitest area </li></ul><ul><li>Biopsy any gross lesion </li></ul><ul><li>Biopsy and do ecc in elongated or abnormally shaped cervices </li></ul>
  35. 35. Cervical Dysplasia <ul><li>Opaque white epithelium </li></ul><ul><li>Occurs at SCJ </li></ul>
  36. 36. Cervical Dysplasia <ul><li>Aceto white epithelium surrounds cervical os </li></ul><ul><li>Internal margins of more densely white </li></ul><ul><li>epithelium </li></ul>
  37. 37. Cervical Dysplasia <ul><li>Diffuse aceta white changes </li></ul><ul><li>Most prominent at 6& 10 o’clock </li></ul>
  38. 38. Severe Dysplasia <ul><li>Marked acetowhite epithelium </li></ul><ul><li>Abnormal raised contour </li></ul>
  39. 39. Carcinoma In Situ
  40. 40. Features of early cancer lesions <ul><li>Oyster shell white </li></ul><ul><li>Rolled edges </li></ul><ul><li>Abnormal vessels </li></ul><ul><li>Friable </li></ul><ul><li>Uneven surface </li></ul>
  41. 42. Invasive Cancer <ul><li>Raised lesion </li></ul><ul><li>Rolled edges </li></ul><ul><li>Raised white epithelium </li></ul><ul><li>Abnormal vessels </li></ul><ul><li>Important to biopsy this </li></ul>
  42. 43. What Needs to be Done in Santa Lucia <ul><li>Develop screening program </li></ul><ul><li>Develop recording system </li></ul><ul><li>Find reliable pathology lab </li></ul><ul><li>Develop follow-up systems </li></ul><ul><ul><li>Untreated positives </li></ul></ul><ul><ul><li>Post treatment patients </li></ul></ul><ul><li>Develop system for referral for treatment </li></ul><ul><li>Teach local physicians and nurses to perform screening </li></ul>
  43. 44. What Have We Done this Week? <ul><li>Screened 80 women ( 7 days) for breast and pelvic cancers </li></ul><ul><ul><li>70 had normal VIA </li></ul></ul><ul><ul><li>10 had abnormal VIA and had cervical biopsies </li></ul></ul><ul><ul><li>3 had cervical polyps removed </li></ul></ul><ul><ul><li>2 required endometrial biopsies for abnormal or postmenopausal bleeding </li></ul></ul><ul><ul><li>1 case of advanced invasive cervical cancer was found </li></ul></ul><ul><li>Developed registration and recording system </li></ul><ul><li>Found a Pathology Lab </li></ul>