1. To pap or not to pap: and what to do when you do Kimberly Swan MD Minimally Invasive Gynecologic Surgery Assistant Professor Ob/Gyn University of Kansas School of Medicine

2. Objectives Importance of cervical cancer screening Current guidelines for screening Management of abnormal results

3. Housekeeping I have no financial disclosures Please get out your cell phones

4. American Society for Colposcopy and Cervical Pathology

5. Cervical Cancer: US Trends US Estimates in 2014: 12,360new diagnoses 4,020 deaths

6. Cervical Cancer Screening Most successful cancer screening program in the US 70% reduction in cervical cancer deaths in past 60 years Most expensive cancer screening program in the US 1960 was the year of “Cervical Cancer Prevention Year” Yearly pap smears was completely arbitrary and not based on evidence

7. Cervical Cancer Estimates of 50% of the women in whom cervical cancer is diagnosed never had cervical cytology testing Another 10-20% have not been screened within the 5 years before diagnosis

8. Guidelines Hard to remember and always changing! ASCCP 2001, 2006, 2008, 2012 Its OK to look it up! Use the app!

9. ACOG Practice Bulletin #131 Cervical Cancer Screening November 2012 (updated from 2009) 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors Published April 2013 Revision of 2006 Guidelines

10. 2012 Guidelines Routine screening Start screening at age 21 Age 21-24 Q 3 years cytology only (no reflex HPV for ASCUS) Age 25-29 Q 3 years cytology only Age 30-64 Q 5 with co-testing (Preferred) Age 30-64 Q 3 cytology (Acceptable) > 65 – No screening after adequate negative prior results S/P Hysterectomy—no more screening if no history of CIN 2/3+ in past 20 years

11. Fear about not doing Pap yearly? A modeling study examined outcomes for women aged 20 years and screened over a 10-year period The number of colposcopies would be reduced by over one half (187/1,000 women screened at 3 years verses 403/1,000 screened annually) Marginal difference in lifetime cancer risk (0.69% verses 0.33%)

12. HPV Oncogenic and Nononcongenic No role for low risk HPV testing Most are transient Unsure about factors that make HPV persist Most important is genotype HPV 16 has highest carcinogenic potential (55-60%) HPV 18: 10-15% Associated with adenocarcinoma Smoking, compromised immune system and HIV increase likelihood

13. HPV and adolescents Most young women will clear HPV in 8 months Reduction in 85-90% viral load over 8-24 months in women younger than 21 High rate of prevalence in adolescents 25% of 14-19 yo are HPV+ 27% HPV+ in 20-25 yo

14. HPV ages 30-65 Natural course of HPV is same as young woman BUT HPV detection is more likely to reflect persistent HPV

15. HPV Vaccination Currently available HPV vaccines could potentially reduce the incidence of cervical cancer by 70% Unfortunately, the proportion of adolescents who have received all 3 doses of the HPV vaccine in the U.S. is approximately 32%, compared with 70-76% in other developed countries such as Australia and the UK

16. The Plug for HPV Vaccination Just ask! (9-26yr) One dose at 0, 2 and 6 months If they have started but not completed they can restart at the next dose (no need to start over) Can be given even if already HPV positive, <1% chance of being exposed to all 4 types

17. Clinical application

18. Case 1 16 yo G0, sexually active for 3 years with 4 partners presents for contraceptive counseling. How will you assess her this visit? A.Pap/GC & chlamydia/pelvic B.Pap/pelvic/urine GC & Chlamydia C.No pap/ pelvic/ GC & chlamydia D.No Pap/ No pelvic/ urine GC &chlamyida

19. Age <21 years Begin cervical screening at age 21 1-2 cases per year of 1,000,000 females ages 15-19 Increases anxiety, morbidity and expense HIV: CDC recommends pap twice in year that HIV diagnosed and annually thereafter ACOG: annual cytology at starting at 21

20. Case 2 17 yo G0 sexually active female moved to KC and seeing you to establish care. 2 months ago had pap with ASCUS. What do you do? A.Triage based on HPV B.Colposcopy C.Repeat pap in 6 and 12 months D.Cytology in 1 year

21. Inadvertent Screen New paradigm for cervical cancer screening for adolescents HPV is widespread in adolescents Cervical cancer is very rare in adolescents Most SIL regresses spontaneously Treatment of cervical dysplasia is associated with perinatal risk

22. Case 3 30 yo G2 for annual exam. At age 27 had negative pap and no abnormals. What do you do? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

23. Case 3 Returns as negative cytology and negative HPV. When should you screen her again for cervical cancer? A.1 year B.2 years C.3 years D.5 years

24. Case 4 35 yo G3P2 for annual exam. No abnormals and last cytology 3 years ago. How do you screen? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

25. Case 4 Result: Unsatisfactory due to inadequate cellularity of less than an estimated 8,000 to 12,000 well-preserved/well- visualized squamous cells on a conventional smear, or less than 5,000 well-preserved/well-visualized squamous cells on a liquid-based preparation. HPV Negative A.Repeat in 5 years B.Repeat in 3 years C.Repeat in 1 year D.Repeat in 2- 4 months

26. Unsatisfactory Pap Unsatisfactory pap: No, unknown or Negative HPV repeat in 2-4 months Positive HPV test repeat in 2-4 months If 2 consecutive unsatisfactory paps Coloposcopy

27. Case 5 31 yo with distant history of ASC-US for annual. Last cytology 3 years ago. How do you screen? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

28. Case 5 Result: Lack of endocervical/transformation zone component. Negative for intraepithelial lesion or malignancy. HPV negative. A.Repeat in 2-4 months B.Repeat 1 year C.Repeat 3 years D.Repeat in 5 years

29. Absent EC/TZ Cytology Negative with Absent or Insufficient EC/TZ component 21-29: routine screening > 30 yo: No/Unknown HPV: HPV testing preferred Cytology in 3 years acceptable Positive HPV Co-testing in 1 year or genotype Negative HPV Routine screening

30. Case 6 42 yo G2P2 new patient to your clinic. Per patient no abnormals in past. Last pap > 7 years ago. What would you like to do? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

31. Case 6 Results: Pap negative and Positive HPV. What would you like to do? A.Repeat pap and HPV in 1 year B.Repeat pap and HPV in 3 years C.Check 16/18 HPV assay D.Colposcopy

32. HPV positive, cytology negative Occurs in 11% of women aged 30 to 34 years; 2.6% of women aged 60 to 65 years Option 1: repeat co-testing in 12 months If HPV-positive or ASC-US+: colposcopy If HPV-negative or Cytology negative: rescreen with co- testing in 3 years Option 2: reflex test for HPV16 or HPV16/18 genotypes If HPV16 or HPV 16/18 positive: colposcopy If HPV16 or HPV 16/18 negative: co-test in 12 months Then manage as in option 1

33. Case 7 38 yo G4P4 annual exam. Last co-testing 5 years ago was negative. How do you screen? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

34. Case 7 Result: ASC-US and HPV Positive. What do you do next? A.Colposcopy B.Repeat co-testing in 6 and 12 months C.Repeat co-testing in 12 months D.Repeat co-testing in 3 years

35. ASC-US Most common cytologic abnormality About half are not associated with HPV ASC-US/HPV+ Colposcopy recommended If no CIN co-test in 1 year and if negative return to routine screening

36. Alternative ending to Case 7 Result: ASC-US and HPV Negative. What do you do next? A.Colposcopy B.Repeat co-testing in 6 and 12 months C.Repeat co-testing in 12 months D.Repeat co-testing in 3 years

37. ASC-US/HPV negative Repeat co-testing in 3 years ASCUS/ HPV unknown Reflex HPV preferred Repeat cytology in 1 year acceptable

38. Case 8 21 yo for first pap smear. How do you screen? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

39. Results: ASC-US How do you manage? A.Colposcopy B.Repeat cytology in 6 and 12 months C.Repeat cytology in 12 months D.Repeat co-testing in 12 months

40. ASCUS in 21-24 ASC-US in 21-24 years Repeat cytology is preferred Repeat at 12 month intervals X 2 Reflex HPV is acceptable If Positive HPV repeat cytology in 12 months If HPV negative routine screening in 3 years

41. Case 8 She returns in one year at age 22 and pap is ASC-US. (now 2012 ASC-US and 2013 ASC-US) What do you do now? A.Colposcopy B.Repeat cytology in 6 and 12 months C.Repeat cytology in 12 months D.Repeat co-testing in 12 months

42. Case 8 Returns one year later at age 23. She has had 2012 & 2013 ASC-US. Her 2014 pap is still ASC-US. What do you do? A.Colposcopy B.Repeat cytology in 6 and 12 months C.Repeat cytology in 12 months D.Repeat co-testing in 12 months

43. Women age 21-24 Initial: ASC-US or LGSIL 12 month: Perform cytology ASC-H, HSIL colposcopy Negative, ASC-US or LGSIL repeat in 12 months (the 24 month mark) 24 month: Cytology Negative –if 2 nd consecutive negative may return to routine screening If ASC-US or worse colposcopy

44. Elderly ASCUS ASC-US > 65 Same management as 30-64 but can’t exit screening on ASC-US

45. Case 9 45 yo for gyn exam. Her last pap in your records was co- testing 3 years ago and was negative cytology and HPV. A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

46. Case 9 Look closer and actually only cytology was done. A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

47. Result: LGSIL/ HPV Positive. What do you do next? A.Colposcopy B.Repeat co-testing in 6 and 12 months C.Repeat cytology in 12 months D.Repeat co-testing in 12 months

48. LGSIL over 24 Management LGSIL (over age 24) IF no HPV or HPV positive colpo HPV Negative Repeat co-testing in 1 year If HPV+ OR ASC-US or worse colpo If co-testing negative Repeat co-testing in 3 years

49. Case 10 24 yo has not been seen for any gyn care. What would you do? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

50. Result: LGSIL. Now what would you do? A.Colposcopy B.Repeat cytology in 6 and 12 months C.Repeat cytology in 12 months D.Repeat co-testing in 12 months

51. Management LGSIL in 21-24 Repeat cytology in 12 month intervals If repeat is negative/ ASC-US / LGSIL repeat cytology in 12 month (now 24 months from initial visit) If repeat ASC-H or HSIL+ colposcopy

52. Case 11 58 yo postmenopausal female for annual exam. Unsure of last screening but never had abnormal paps. What would you do? A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

53. Case 11 Result: LGSIL/ HPV Positive. What do you do next? A.Colposcopy B.Repeat cytology in 6 and 12 months C.Repeat cytology in 12 months D.Repeat co-testing in 12 months

54. Management LGSIL in postmenopausal LGSIL and unknown HPV HPV test, repeat cytology in 6/12 months or Colposcopy LGSIL and Positive HPV Colposcopy LGSIL and negative HPV Repeat cotesting in 12 months

55. Case 12 34 yo for annual exam. Cytology only 3 years ago. A.No cervical cancer screening needed B.Cytology alone C.Cytology and reflex HPV D.Co testing: Cytology and HPV

56. Case 12 Results: ASC-H and HPV unable to be obtained. What is next? A.Colposcopy B.Repeat cytology in 6 and 12 months C.Repeat co-testing in 12 months D.HPV testing

57. Management ASC-H Colposcopy regardless of age Management HGSIL Immediate excision is acceptable Except in 21-24 yo Colposcopy is acceptable (regardless of HPV)

58. Case 13 45 yo G0 atypical glandular cells. HPV not done. What do you need to do? A.HPV testing B.Colposcopy and ECC C.Colpo, ECC and EMB D.Colpo, ECC, EMB and HPV

59. Management of AGC Colposcopy with ECC ( perform HPV if not done) EMB if > 35 yo or < 35 and high clinical suspicion Management of atypical endometrial cells EMB and ECC

60. Case 14 42 yo premenopausal female with no symptoms and “benign appearing endometrial cells in a woman over 40.” Next step? A.Colpo, ECC and EMB B.EMB C.Routine screening

61. Management of asymptomatic premenopausal Benign Endometrial cells, endometrial stromal cells, histiocytes No further evaluation Postmenopausal women Endometrial assessment

62. Just when you get it… FDA Advisory board recently approved primary HPV testing as a screening test for cervical cancer

63. Thank you Questions for me?