1. cap.org v. 1 Gynecologic Consensus Conference Topic Group V: Monitoring of HPV Rates June 4, 2011

2. Work Group 5 Christine Booth MD, FCAP, Chair Michael Henry MD, FCAP, Senior Author Carol Filomena MD, FCAP Marilee Means PhD, SCT(ASCP) Patricia Wasserman MD, FCAP Christine Bashleben, MT(ASCP) CAP staff 2 © 2011 College of American Pathologists. All rights reserved.

3. Background ASCCP 2006 Consensus Guidelines o Provides revised evidence-based consensus guidelines for managing women with − Abnormal cervical screening test results − Cervical intraepithelial neoplasia (CIN) or Adenocarcinoma in situ (AIS) 3 © 2011 College of American Pathologists. All rights reserved.

4. ASCCP 2006 Consensus Guidelines HPV TESTING Use only analytically and clinically validated tests Test for high-risk HPV types only (there is no role for low-risk HPV testing in a cervical cancer screening program) Screening can use co-testing with Pap and HPV in women over 30 years. If both tests are negative, re-screen in three years. 4 © 2011 College of American Pathologists. All rights reserved.

5. ASCCP 2006 Consensus Guidelines HPV TESTING HPV testing in adolescents is unacceptable Reflex HPV testing for the triage of women with ASC-US is preferred, except in women 20 years of age or under Reflex HPV testing for the triage of postmenopausal women with LSIL is an acceptable choice 5 © 2011 College of American Pathologists. All rights reserved.

6. ASCCP 2006 Consensus Guidelines ASC-H o >65% HPV +  no value of reflex HPV o No changes from 2001 consensus o “Review all material” eliminated o Management same as ASC-US + HR-HPV+ 6 © 2011 College of American Pathologists. All rights reserved.

7. Survey Results 7 © 2011 College of American Pathologists. All rights reserved.

8. HPV results obtained at the time of the Pap test are routinely incorporated into the Pap report: (n=525) Yes 61.9 % No 38.1 % 8 Original Survey Results: HPV testing practices © 2011 College of American Pathologists. All rights reserved.

9. How are HR-HPV tests for ASC-US ordered? (n=518; multiple responses allowed) Ordered as a "reflex test" by providers Ordered reflexively by the laboratory independent of the primary provider initial order Offered for reflex testing for women under 21 years of age 9 Original Survey Results: HPV testing practices 87.6% 23.4 % 7.9 % © 2011 College of American Pathologists. All rights reserved.

10. Laboratory limits ASC-US reflex testing to women over the age of 20: (n=512) Yes 15.6 % No 84.4 % If no, why? (from online survey): Clinician driven Patient demands Resolve diagnostic dilemmas Ordered out of habit Original Survey Results: HPV testing practices 10 © 2011 College of American Pathologists. All rights reserved.

11. 71% of respondents will perform reflex HR-HPV in ASC-US in women under 20 at clinician’s insistence 51% of respondents will call clinician to educate about published guidelines before performing reflex HR-HPV in ASC-US in women under 20 6% of respondents will not perform reflex HR-HPV in ASC-US in women under 20 despite clinician’s insistence Some respondents will perform reflex HR-HPV testing in women under 20 at clinician’s insistence and will include a comment in the report indicating that “modern guidelines do not recommend HPV tests for women equal and less than 20 years of age and if obtained, the results should be ignored for management.” Some respondents require that clinicians who wants reflex HR-HPV testing in women under 20 submit a separately collected test directly to virology © 2011 College of American Pathologists. All rights reserved. 11 Online Question Results 11 © 2011 College of American Pathologists. All rights reserved.

12. Which HR-HPV tests are reflexively offered from a cytology specimen? (n=520; multiple responses allowed) ASC-US reflex 90.6% ASC-H reflex 47.1% AGC or other glandular abnormalities 28.3% Pap test with any squamous epithelial abnormality 23.5% LSIL with a Pap test regardless of age 20.8% LSIL reflex in postmenopausal women 14.8% Original Survey Results: HPV testing practices 12 © 2011 College of American Pathologists. All rights reserved.

13. Does your lab offer HPV reflex testing on ASC-H? 50% offer reflex HR-HPV testing for ASC-H results Some respondents state that knowledge of HPV in ASC-H is beneficial in the following cases: o No colposcopic follow up if HPV is negative o If HPV negative, patient returns to routine testing o Useful in resolving diagnostic dilemmas with confidence o Useful in older women with negative history o Useful in pregnant women o Helps PCP decide to go to LEEP or not © 2011 College of American Pathologists. All rights reserved. 13 Online Question Results 13 © 2011 College of American Pathologists. All rights reserved.

14. If an HR-HPV test is not ordered reflexively on a Pap test by the submitting clinician, does the pathologist have the discretion to order an HR-HPV test? (n=520) Yes 38.7 % No 61.3 % Original Survey Results: HPV testing practices 14 © 2011 College of American Pathologists. All rights reserved.

15. Laboratory finds it useful to order HR-HPV testing independently of the clinician to resolve diagnostic discrepancies between the cytotechnologist and pathologist in Pap test diagnosed as the following: (n=129; multiple responses allowed) ASC-US 75.2 % ASC-H 58.9 % AGC 31.0 % HSIL 19.4 % LSIL 18.6 % SCC 7.8 % ADC 5.4 % Original Survey Results: HPV testing practices 15 © 2011 College of American Pathologists. All rights reserved.

16. If you do use HR-HPV results to resolve diagnostic discrepancies, please explain how: To fine tune ASC-US criteria To aid in the CT-P disagreements for ASC-US cases In borderline Pap interpretations o HPV negative cases results in re-evaluations o HPV positive cases results in re-evaluations To resolve diagnostic dilemmas at any age © 2011 College of American Pathologists. All rights reserved. 16 Online Question Results 16 © 2011 College of American Pathologists. All rights reserved.

17. 1.Smaller labs are more likely to reflexively order HPV testing independent of the initial order ( P =0.001) 2.Larger labs are more likely to reflexively order HPV testing with any squamous abnormality ( P =0.001) 17 Survey Results: Lab Volume Analysis for HPV Testing Practices © 2011 College of American Pathologists. All rights reserved.

18. Laboratory offers low-risk HPV testing: (n=520) o Never45.6% o Only on request39.2% o Routinely bundled with HR-HPV11.9% o Other 3.3% 18 Original Survey Results: HPV testing practices © 2011 College of American Pathologists. All rights reserved.

19. Statements Based on Survey, Literature and Expert Consensus Laboratories should only offer HR-HPV testing for GYN specimens Laboratories should encourage clinicians to consider the latest consensus guidelines in ordering HR-HPV tests on GYN specimens Laboratories should be cautious in using HPV test results to change or influence cytologic interpretations 19 © 2011 College of American Pathologists. All rights reserved.

20. Consensus Questions 20 © 2011 College of American Pathologists. All rights reserved.

21. 46. Should HR-HPV tests be ordered by the laboratory to be used as a diagnostic test to aid in morphologic dilemmas and resolve diagnostic discrepancies? A. Yes 15.2% B. No 75.8% C. Unsure 9.1% 21 Consensus Question - Vote © 2011 College of American Pathologists. All rights reserved.

22. Consensus Question - Vote 47. HR-HPV results should aid in down- or upgrading of Pap test interpretations when available prior to sign-out. A. Yes 8.1% B. No 83.9% C. Only in certain circumstances 8.1% 22 © 2011 College of American Pathologists. All rights reserved.

23. 48. It is not appropriate to offer LR-HPV testing on Pap tests: A.For any clinical circumstance. 80.6% B.Disagree. It should be offered when clinically requested. 17.91% 23 Consensus Question - Vote © 2011 College of American Pathologists. All rights reserved.

24. HR-HPV rates are monitored to determine potential trends in accuracy of diagnoses: o ASC-US reflex HR-HPV results (n=510) −Yes53.9% −No46.1% o HPV DNA Results (n=364) −Yes32.7% −No 67.3% 24 Original Survey Results: HPV for Quality Assessment © 2011 College of American Pathologists. All rights reserved.

25. Monitoring of HPV rates (n=392; multiple responses allowed) Laboratory CytotechPathologist ASC-US53.3%13.8%21.4% NILM21.4% 5.9% 5.9% LSIL17.9% 4.3% 5.9% HSIL14.8% 3.3% 4.6% 25 Original Survey Results: HPV for Quality Assessment © 2011 College of American Pathologists. All rights reserved.

26. HPV results are compared to ASC-US/SIL ratios for pathologists to determine potential trends in over or under diagnosis? (n=513) Yes 28.8% No71.2% 26 Original Survey Results: HPV for Quality Assessment If no, why not? (from online survey) Too complex to get data Pap and HPV results in separate systems Does not affect pathologist sign-out tendencies © 2011 College of American Pathologists. All rights reserved.

27. CAP Checklist CYP.07653 HR-HPV Records If available, records are maintained for high-risk human papillomavirus (HR-HPV) tests performed on ASC-US including: 1.Total number of HR-HPV tests performed on ASC-US cases 2.Total number of POSITIVE HR-HPV ASC-US cases NOTE: The percentage of ASC-US cases with a positive HR-HPV result may be a helpful quality metric for both overall laboratory performance and individual performance of pathologists, especially when combined with an individual's ASC-SIL ratio. Data for other HR-HPV testing results (e.g. co-testing with a Pap test in women > 30 years of age) may also be helpful quality metrics but should be kept separately. 27 © 2011 College of American Pathologists. All rights reserved.

28. Statements Based on Survey, Literature and Expert Consensus While there is significant variability in interinstitutional HPV-positive rates in ASC-US Pap tests, monitoring the HPV-positive rate in ASC-US Pap tests is a valuable broad measure of quality. Performance beyond 2 SD’s of the mean should prompt reassessment of diagnostic criteria used in the evaluation of Pap tests and/or investigation of the prevalence of HPV positivity in the population from which the Pap tests are obtained. (Tworek et al, Arch Pathol Lab Med. 2007;131:1525–1531) 28 © 2011 College of American Pathologists. All rights reserved.

29. Statements Based on Survey, Literature and Expert Consensus Monitoring the HPV-positive rate in other diagnostic categories such as LSIL and the comparison of these HR-HPV rates to published benchmarks is also a valuable broad measure of quality for a laboratory and possibly for individuals. 29 © 2011 College of American Pathologists. All rights reserved.

30. Statements Based on Survey, Literature and Expert Consensus When possible, individual ASC-US/HR-HPV results should be compared to ASC-US/SIL ratios for pathologists to determine potential trends in over- and under-diagnosis. 30 © 2011 College of American Pathologists. All rights reserved.

31. Consensus Question - Vote 49. If possible, ASC-US/HR-HPV results should be compared to ASC-US/SIL ratios per pathologist as a general quality monitor. A. Yes 58.5% B. No 18.9% C. Unsure 22.6% 31 © 2011 College of American Pathologists. All rights reserved.

32. 50. ASC-US reflex HR-HPV results should be monitored to determine potential trends in accuracy of diagnoses: A. Yes 71.9% B. No 18.8% C. Unsure 9.4% 32 Consensus Question - Vote © 2011 College of American Pathologists. All rights reserved.

33. 51. HR-HPV DNA results for other diagnostic categories should be monitored to determine potential trends in accuracy of diagnoses. A. Yes 32.3% B. No 50.8% C. Unsure 15.4% D. Other 1.5% Consensus Question - Vote 33 © 2011 College of American Pathologists. All rights reserved.

34. 73. Laboratories should routinely document all available HPV test results performed over the last five years preceding histopathologic diagnoses of cervical carcinoma including laboratory site and date where each HPV test was performed. A. Yes 69.6% B. No 17.9% C. Unsure 12.5% Additional Questions - Vote © 2011 College of American Pathologists. All rights reserved.

35. 74. Laboratories should routinely document all available HPV test results performed over the last five years preceding histopathologic diagnoses of cervical carcinoma including specific HPV test and platform, including FDA approved versus laboratory developed test A. Yes 80.1% B. No 9.6% C. Unsure 9.6% Additional Questions - Vote © 2011 College of American Pathologists. All rights reserved.

36. 75. Is it appropriate for a lab to order a HR-HPV test as a diagnostic test independent of the clinician? A. Yes 6% B. No 84% C. Unsure 10% Additional Questions - Vote © 2011 College of American Pathologists. All rights reserved.