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1. Management of the Abnormal Pap Smear, Cervical Dysplasia, and Cervical Cancer Todd D. Tillmanns MD Assistant Professor Department of Obstetrics & Gynecology Division of Gynecologic Oncology University of Tennessee and West Clinic E-mail: [email_address]

4. Relative Risk of Cervical Cancer by HPV Type

5. Electron Micrograph of HPV

6. Cervical Histology Showing HPV & Koilocytes

7. Cervical Cytology Showing HPV & Koilocytes

8. Risk of Progression to Cancer >12% 5% 1% Ostor AG. CIN III CIN II CIN I Author

14. Repeat Cytology @ 4 - 6 mos HPV DNA Testing Colposcopy Preferred if liquid-based cytology or co-collection available “ When liquid-based cytology is used, or when co-collection for HPV DNA testing can be done, "reflex" HPV DNA testing is the preferred approach” ASCCP Management Guidelines ASC-US: HPV Testing Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ, for 2001 ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002;287:2120-2129.

15. Patient Management Using HPV Triage ASCUS HPV TEST Low Risk + or HPV – HPV + Repeat Pap and/or HPV Test in 12 mo. or return to routine screening at discretion of clinician COLPOSCOPY BIOPSY/ABLATION

26. Transformation Zone

31. Cervical Conization

35. 44 40 41 30 29 47 51 39 5 3 27 19 16 42 31 45 43 1 20 2 28 15 8 18 13 14 4 6 10 38 48 37 50 34 33 11 9 7 21 24 22 17 32 23 25 46 49 Age-adjusted Death Rate (Rank) 2.6-2.3 (31-40) 3.1-2.6 (22-30) 3.4-3.1 (11-21) 3.8-4.8 (1-10) Age-adjusted* Death Rates and Rank from Cervical Cancer United States 1996-2000 *Age-adjusted to 2000 population -Rank 1 is worst; 51 is best. -Rates are per 100,000 36 35 12 26 2.3-1.8 (41-51)

36. Lifetime Probability of Developing Cancer, by Site, Women, US, 1997-1999 Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002. Site Risk All sites 1 in 3 Breast 1 in 8 Lung & bronchus 1 in 17 Colon & rectum 1 in 18 Uterine corpus 1 in 37 Non-Hodgkin lymphoma 1 in 56 Ovary 1 in 58 Pancreas 1 in 80 Melanoma 1 in 81 Urinary bladder 1 in 88 Uterine cervix 1 in 123

37. Test Trends in Recent* Pap Prevalence (%), by Educational Attainment, Women 25 and Older, US, 1992-2000 * A Pap test within the past three years. **Includes fewer than 50 states and District of Columbia Source: Behavior Risk Factor Surveillance System, 1992-1995, 1996-1997, 1998, 1999, 2000, National Center for Chronic Disease Prevention and Health Promotion, Center for Disease Control and Prevention,1997, 1999, 2000, 2000, 2001 Prevalence (%) Less than High School Some college or greater High School graduate All women 18 and older

38. Incidence and Mortality Rates 1997-2001 by Race/Ethnicity American Cancer Society 2005 Mortality rates per 100,000 based on 2000 US standard population 3.6 2.8 2.8 5.6 2.6 Latina American Indian Asian African American White

39. Cancer Survival*(%) by Site and Race,1992-1998 *5-year relative survival rates based on follow up of patients through 1999. Source: Surveillance, Epidemiology, and End Results Program, 1973-1999, Division of Cancer Control and Population Sciences, National Cancer Institute, 2002. All Sites 64 53 11 Breast (female) 88 73 15 Colon & rectum 63 53 10 Esophagus 15 8 7 Leukemia 47 38 9 Non-Hodgkin lymphoma 56 46 10 Oral cavity 59 35 24 Prostate 98 93 5 Urinary bladder 82 65 17 Uterine cervix 72 60 12 Uterine corpus 86 61 25 Site White % Difference African American

50. Advanced Cervical Cancer EB=external beam, ICRT=intracavitary radiation therapy, P=platinum, F=5-FU, HU=hydroxyurea 65 65 47 76 63 67 57 3 yr Med Surv (%) 0.001 (0.57) 0.001 (0.55) 0.03 (0.79) PFS P-val (RR) EB + ICRT + P EB + ICRT + PFHU EB + ICRT + HU 176 173 177 IIb-IVa Rose et al. 1999 EB + ICRT + PF EB + ICRT 195 193 IIb-IVa Morris et al. 1999 EB + ICRT + PF EB + ICRT + HU 177 191 IIb-IVa Whitney et al. 1999 Treatment n Stage Author

53. Results GOG 179 Long III HJ. SGO 35 th Annual Meeting 2004 [Abstract 9]

54. Progression-free survival

55. Overall survival

57. Adverse Events GOG 179 Long III HJ. SGO 35 th Annual Meeting 2004 [Abstract 9]

62. THANK YOU ! Questions / Comments ?