1. 2006 ASCCP Consensus Guidelines Anne L. Kittendorf, MD FAAFP Assistant Professor University of Michigan Department of Family Medicine

2. Objectives Review Evidence Behind New Guidelines New Algorithms Highlight Important Changes

3. Why new guidelines? ASCCP 2001 Consensus Guidelines New Data ALTS HPV prevalence 2004 Interim Guidance

4. Cervical Cancer: US Trends in Incidence and Mortality National Cancer Institute

6. Insinga RP et al Am J Obstet Gynecol 2004 Chesson HW et al Perspect Sex Reprod Health 2004

7. HPV Epidemiology in US Lifetime risk is at least 50% for infection Incidence: 6.2 million/yr Prevalence: 20 million

8. Hierarchy of clinical/subclinical HPV infection in US ages 15-49 Koutsky Am J Med 1997

9. HPV Epidemiology in US Over 200 types of HPV HPV-1:plantar warts HPV-2,4:common warts HPV 6,11:genital warts 20 HPV types cause cancer 80% in U.S. from 16, 18, 31, 45 Hybrid Capture 2 (FDA Approved) detects: 16, 18, 31, 33, 35, 39, 45

10. Prevalence as a function of Lifetime Partners Burk RD et al. J Infect Dis 1996

11. Natural History of High Risk HPV 70% of women become HPV negative within 1 year 90% within 2 years 10% will develop persistent HPV infection

12. How good is HPV testing? A single negative HPV DNA test carries a negligible risk for CIN 3 (0.24% at 45 months, 0.87% at 10 years) Clavel 2001 Detection Rate of CIN2 or greater (Sensitivity) HPV DNA Testing *Less Specific 99.9% Conventional Cytology58% Liquid-based Cytology84%

13. How good is HPV testing? Conversely, HPV positive with Negative Pap: Predictive of CIN2,3 4.4% at 45 months 7% at 10 years (Sherman ME)

14. Let’s Limit Unnecessary Paps (#1)! HPV Testing and Low Risk Women For women 30 and over Perform both cytology AND HPV testing If both negative, re-screen in 3 years –Remember, risk of CIN3 is 0.24% at 45 months If HPV positive, cytology negative, re-screen in 12 mos

15. Terminology Reminder BETHESDA: Cytology CIN GRADING: Histology ASCUSAtypia LSILCIN I HSILCIN II Carcinoma In SituCIN III

16. Adults ASCUS- No Changes from Interim >CIN2 is 10%, triage with HPV testing to prove infection. If negative, repeat in 12 months If positive—to Colp If Colp negative, repeat pap at 6&12 mos, OR HPV at 12 mos Or direct to colposcopy Or cytology at 6 & 12 mos

17. Adults with ASC-H Colposcopy Recommended Prevalence of CIN 2 or greater as high as 50% HPV testing not included in algorithm, but negative is likely reassuring of absence of significant disease (but still do colposcopy)

18. Adults with LSIL/CIN 1 HPV testing not useful: 86% HPV positive 28% will actually have higher grade lesions Direct to Colposcopy: However, low risk of Cancer If LSIL proceeded by HSIL or AGC-NOS, greater than 90% with CIN2 or greater

19. Adults with LSIL/CIN 1 LSIL is a predictor of CIN2, even with negative Colposcopy 12-28% will develop CIN 2 or greater within 2 years Therefore, if Colp -, HPV testing at 12 mos or cytology at 6,12 mos

20. HSIL/CIN 2,3 Adult Nonpregnant =Cancer Precursor 75% will have CIN 2 or greater 12% of CIN3 will develop cancer 1-4% will have invasive cancer Observation Unacceptable: “See and Treat” vs. Colposcopy If colposcopy normal, can retest at 6&12 mos OR excisional procedure

21. Status Post Excisional Procedure If HPV +, increased risk of residual disease or progression Post Treatment status –With HPV testing –With Cytology –With Cytology + Colposcopy Zielinski 2004 NPV HPV Negative 98% Cytology Negative 93% Resection Margins Negative 91%

22. Adenocarcinoma In Situ (AIS) High Grade Lesion HPV testing, Colposcopy, and endocervical assessment Colposcopy may be unremarkable--If negative, excisional procedure If histology positive, Hysterectomy Conservative approach acceptable for those desiring fertility

23. Atypical Glandular Cells (AGC) Benign lesions most common, but pathology 38% of time CIN most common in women <35 Over 35, risk of cancers increases HPV testing, Colposcopy, Endocervical Assessment For women over 35 or risk factors, endometrial biopsy

24. Adolescents 20 or Younger 74% of new infections are in this age group Prevalence up to 54% 9.2 million currently infected Cervical cancer only 0-3 per million women years in adolescents Winer RL et al Am J Epidemiol 2003

25. Adolescents: 20 or Younger Most infections occur soon after coitarche Predominantly columnar epithelium = thinner Squamous Metaplasia = biologically active Increased rate of HPV with concomitant STIs Adolescent Coitarche Increases Risk of Cancer as Adult? Having a new partner > # of partners?

26. Let’s Limit Unnecessary Paps (#2)! Teens: When to Start Screening? 90% infections clear within 2 years Avoid unnecessary harm through aggressive screening/treatment! Begin 3 years after coitarche OR age 21 (USPSTF)

27. Teens: What about HPV testing? HPV test not helpful Treat LSIL and ASCUS as likely transient HPV infections that need to be monitored Repeat cytology in 12 months Colposcopy for progression to HSIL or if any cytologic abnormality persists 24 mo.

28. Teens: HSIL or CIN 2,3 Incidence is 0.7% (same as older women) Colposcopy Recommended If Colposcopy/Biopsy not high grade: excisional procedure only acceptable if HSIL persists 24 mos If CIN 2: Observation q 6 mos preferred If CIN 2,3 NOS: observe or excise If CIN 3 or unsatisfactory colp: excise

29. Pregnancy and HPV Cancer rate 5 in 100,000 Observe, do not treat! Pregnancy does not accelerate HPV Regression of lesions common 36% of CIN I 48-70% of CIN 2,3

30. Pregnancy and HPV Can defer colposcopy until postpartum for ASCUS or LSIL If HSIL Colposcopy and directed biopsies are safe Endocervical curettage is unacceptable No Excision unless strong suspicion or diagnosis of Cancer

31. Endometrial Cells Histiocytes, and Benign Adenosis are clinically insignificant Endometrial Stromal Cells Benign finding for premenopausal women Postmenopause: 7% with pathology -Endometrial biopsy and endocervical sampling

32. Important References Algorithm PDF –www.asccp.org/consensus/cytological.shtmlwww.asccp.org/consensus/cytological.shtml American Journal of Obstetrics and Gynecology, Oct 07 –www.AJOG.org or www.asccp.org/consensus/cytological.shtmlwww.AJOG.org www.asccp.org/consensus/cytological.shtml –“2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests” –“2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ”

33. Important References Centers for Disease Control and Prevention www.cdc.gov/std/hpv/hpv-clinicians- brochure.htmwww.cdc.gov/std/hpv/hpv-clinicians- brochure.htm American Society for Colposcopy and Cervical Pathology www.asccp.org/edu/practice/cervix.shtml www.asccp.org/edu/practice/cervix.shtml Merck Medicus www.merckmedicus.com/pp/us/hcp/diseasem odules/hpvd/default.jsp