1. Assessing the Burden of HPV-Associated Cancers in the U.S., 1998-2003 (ABHACUS): Monitoring the Impact of Emerging Technologies Using Cancer Registry Data Margaret Watson, MPH ORISE Fellow, Division of Cancer Prevention and Control National Center for Chronic Disease Prevention and Health Promotion

2. Outline u HPV background u ABHACUS project l Rationale l Analysis criteria l Results-burden of HPV-associated cancers u Cervical cancer u Vulvar cancer (vaginal to be discussed later) u Penile cancer u Anal cancer u Oral cavity and oropharyngeal cancers u Conclusions

3. Human Papillomavirus (HPV) u HPV common, sexually transmitted u HPV persistence responsible for development of certain types of cancer u Carcinogenesis is slow u 100 types of HPV l 13-15 HPV types are considered oncogenic l ~70% of invasive cervical cancer HPV 16/18 l ~90% of genital warts HPV 6/11

4. HPV-Associated Cancers and Attributable Fraction due to HPV Cancer site % due to any HPV Infection % of HPV-related which are types 16/18 Cervix10070 Vagina4080 Vulva4080 Anus9092 Penis4063 Oral Cavity 2598 Oropharynx 3595/89 Parkin DM, Bray F. The burden of HPV-related cancers. In: Bosch FX, Cuzick J, Schiller JT, Garnett GP, Meheus A, Franco EL et al., editors. Vaccine: HPV vaccines and screening in the prevention of cervical cancer. 2006. Oropharyngeal from Kreimer et al.

5. Emerging Technologies u Vaccines l 2006- FDA approved Quadrivalent HPV Vaccine (HPV 6, 11, 16,18) u Prevents cervical, vaginal, vulvar precancers l Bivalent HPV Vaccine (HPV 16, 18) undergoing FDA approval u HPV Test l Detects 13 oncogenic types l Used for management of abnormal Pap tests, screening for women over 30 years of age

6. ABHACUS Supplement u Published in 2008 l Journal CANCER, produced by American Cancer Society u 23 articles: l Baseline burden l Overview of HPV l Federal initiatives l State- or area-specific data l Combined datasets

7. ABHACUS Supplement: u 100 Authors and Participants l State Cancer Registries u CA, FL, ID, IL, KY, LA, ME, MI, NM, NY, SD, TN, TX, VA l Academia-Universities and Cancer Centers u Moffitt, University of Hawaii, University of AZ, Case Western, Emory, Johns Hopkins University l National Cancer Institute l American Cancer Society l CDC-Cancer, STD, Immunizations, and HPV Lab u Process l Monthly meetings –criteria for analysis l Peer review

9. Criteria Used for Analysis of Cancer Registry Data Cancer Site ICD-0-3 Site Codes Histologies examined ICD-0-3 Histology Codes Cervix530-539 All carcinomas 8010-8671, 8940-8941 Vagina529 Squamous cell carcinomas 8050-8084, 8120-8131 Vulva510-519 Anus (includes Rectal SCCs) 209-212, 218 Penis600-609 Oral Cavity and Oropharynx 019, 024, 090, 091, 098, 099, 142, 028, 102, 108, 109, 140, 148

10. Syrjanen (2004) J Clin Pathol; Syrjanen (2005) J Clin Virol; Paz (1997) Cancer; Kreimer (2006) Cancer Epi Biomarkers & Prev; Mork (2001) NEJM; Dalgren (2004) Int J Ca; Ritchie (2003) Int J Ca Criteria Used for Analysis of Cancer Registry Data: Oral Cavity and Oropharyngeal Subsites Subsite (limited to SCCs) HPV-DNA positivity rate * Potentially HPV- Associated Tonsil51 % Base of tongue and lingual tonsil40 % Other oropharynx36 % HPV-Unrelated Oral tongue 0% - 25% Other oral cavity Larynx Other oropharynx

11. Criteria Used for Analysis of Cancer Registry Data u Histology l All histologies microscopically confirmed l Analyses examining NPCR/SEER data exclude 8077/2 (intraepithelial neoplasia 3) for vulvar, vaginal, and anal cancers (VIN, VaIN, AIN) u Race/ethnicity l Race separate from Hispanic ethnicity l American Indian/Alaska Native not examined as a separate group

12. Results

13. Invasive HPV-Associated Cancers in Females, 1998- 2003* Site Average Annual Count Incidence Rate 95% C.I. Cervix10,8468.9(8.9, 9.0) Vulva2,2661.7(1.7, 1.7) Vagina6010.5(0.4, 0.5) Anus1,9341.5(1.5, 1.5) Oral cavity & oropharynx 1,7021.3(1.3, 1.4) Total17,34914.0(13.8, 14.0)

14. Invasive HPV-Associated Cancers in Males, 1998- 2003* Site Average Annual CountIncidence rate95% C.I. Penis8280.8(0.8, 0.8) Anus1,0831.0(1.0, 1.0) Oral cavity & oropharynx 5,6585.2(5.1, 5.2) Total7,5687.0(6.9, 7.0)

15. In Situ HPV-associated Cancers in Females, 1998-2003* Site Average Annual Count Incidence rate 95% C.I. Vulva*1,4981.23(1.20, 1.25) Vagina*1620.13(0.12, 0.14) Anus*2130.17(0.16, 0.18) Oral cavity & oropharynx 230.02(0.02, 0.02) Total1,8971.55(1.52, 1.58) *8077/2 excluded

16. In Situ HPV-Associated Cancers in Males, 1998- 2003* Site Average Annual CountIncidence rate95% C.I. Penis4260.40(0.39, 0.42) Anus*2160.19(0.18, 0.20) Oral cavity & oropharynx 610.06(0.05, 0.06) Total7020.65(0.63, 0.67) *8077/2 excluded

17. Rates of Invasive Cervical Cancer by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

18. Cervical Cancer-Results Incidence Rate Average Annual Count Median Age Total8.910,84647 Race White 8.48,57647 Black 12.6*1,57149 API 8.342451 Ethnicity Non-Hispanic 8.49,13148 Hispanic 14.2*1,71545 * p<0.05

19. Rates of Invasive Vulvar Cancer by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

20. Vulvar Cancer-Results Incidence Rate Average Annual Count Total1.72,266 Race White1.82,056 Black1.3*157 API0.4*16 Ethnicity Non-Hispanic1.82,153 Hispanic 1.3*114 * p<0.05

21. Rates of Invasive Penile Cancer by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

22. Penile Cancer-Results Incidence Rate Average Annual Count Total0.8828 Race White 0.8731 Black 0.865 API 0.4*12 Ethnicity Non-Hispanic 0.8722 Hispanic 1.3*106 * p<0.05

23. Rates of Invasive Anal Cancer in Males by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

24. Rates of Invasive Anal Cancer in Females by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

25. Anal Cancer-Results MaleFemale Incidence Rate Average Annual Count Incidence Rate Average Annual Count Total1.01,0831.51,935 Race White1.09271.61,739 Black1.2*1241.3*152 API0.2*80.4*19 Ethnicity Non-Hispanic1.01,0111.51,796 Hispanic0.8*721.5139 * p<0.05

26. Rates of Invasive Oral Cavity/Oropharyngeal Cancer in Males by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

27. Rates of Invasive Oral Cavity/Oropharyngeal Cancers in Females by Census Division Maps developed by James Cucinelli (IMS, Inc.) and Dave Stinchcomb (National Cancer Institute) based on the micromaps design (Carr & Pierson, 1996).

28. Oral Cavity/Oropharyngeal Cancer-Results MaleFemale Incidence Rate Average Annual Count Incidence Rate Average Annual Count Total5.25,6581.31,702 Race White5.14,8931.31,484 Black6.8*6301.5*179 API1.7*640.5*23 Ethnicity Non-Hispanic5.35,3631.41,634 Hispanic3.6*2950.7*69 * p<0.05

29. Results: Conclusions u Total of 149,507 cases of invasive HPV- associated cancer during 1998-2003 l 104,097 among women l 45,410 among men u Epidemiology of HPV-associated cancers varies by cancer site l Association with HPV varies l Cofactors vary

30. Conclusion: Limitations and Possibilities u No information on HPV in specific tumors l Special projects will type HPV in tumor tissue u No information on vaccine history l Potential to link vaccine and cancer registry data l Potential to correlate vaccine rates and cancer rates in specific geographic areas u Not all registries met data qualifications l More data included in more recent years u In situ cervical tumors not collected; vulvar, vaginal and anal intraepithelial neoplasia lesions (VIN/VAIN/AIN 3) inconsistently collected l Michigan continued to collect in situ cervical tumors after 1996 decision

31. Conclusions u First assessment of overall burden of HPV- associated cancers in the US using large population u Histology categories, criteria for analysis standardized and clearly defined for future re- analyses l Not based on HPV attributable fraction u Inclusion of some rare cancers by racial, geographic variation

32. Acknowledgements u Methods co-authors: Mona Saraiya, Faruque Ahmed, Cheryll Cardinez, Hannah Weir, Marsha Reichman, Tom Richards u Djenaba Joseph u Xiaocheng Wu u Blythe Ryerson u Brenda Hernandez u Dave Stinchcomb u ABHACUS Steering committee

33. Thank you Meg Watson 770-488-3097 eze5@cdc.gov