1. June 27, 2005 Predicting Human Papilloma Virus Prevalence and Vaccine Policy Effectiveness Courtney Corley Department of Computer Science University of North Texas

2. June 27, 2005 Human Papilloma Virus Sexually Transmitted Virus which can lead to cervical dysplasia (cancer). Types {16,18,31,45} account for 75% of cervical cancer Found in 99.7% of all cervical cancers

3. June 27, 2005 Human Papilloma Virus 80% of the sexually active adult population will contract HPV 2004 U.S. spent over $1.6 billion in treating symptoms of HPV $5-6 billion spent on screening tests such as pap smears. 2005 U.S. estimates 13,000 cases of cervical cancer More than 5,000 will die from cervical cancer

4. June 27, 2005 HPV Vaccine Exciting news! Several candidate vaccines are in phase III testing with the FDA Drug companies are currently in licensing arbitration

5. June 27, 2005 Sexually Transmitted Disease Modeling Transmission Dynamics Transmission Dynamics Contact rates and activity groupsContact rates and activity groups Risk of TransmissionRisk of Transmission Sexual activity and sexually active populations Sexual activity and sexually active populations Sexual mixing Sexual mixing Demographic StratificationDemographic Stratification

6. June 27, 2005 Who do we model? We model the individuals who are currently sexually active and able to contract the disease

7. June 27, 2005 Sexually Active The range in years in which an individual changes sexual partners more than once per year on average We define the sexually active population age range as:

8. June 27, 2005 Sexually Active Ages Given this concept of sexual activity the age ranges for each model are : Age (years) 02040 1530 HPV 15-30

9. June 27, 2005 Transmission Dynamics Modeling sexually transmitted diseases is similar to modeling other infectious diseases, they depend on: Population Mixing Contact Rates

10. June 27, 2005 Contact Rates The contact-rate is the number of partner changes per year We define three sexual activity groups by contact-rates: Low Moderate High

11. June 27, 2005 Sexual Activity Groups [partner changes/year]

12. June 27, 2005 Risk of Transmission The risk of transmission is based on two factors: The average number of sexual encounters with one partner The risk of transmission in one sexual encounter

13. June 27, 2005 Relative Risk of Transmission The average is taken to determine the relative risk for HPV infection: HPV Male-to-Female 80% Male-to-Female 80% Female-to-Male 70% Female-to-Male 70%

14. June 27, 2005 Demographic Stratification To accurately model geographic regions, we categorize the population further: Demographics RaceAge

15. June 27, 2005 Demographic Stratification We have our three activity groups: Low Moderate High And we have our demographic parameters Now we combine: a demographic trait the sexual activity classes to represent the demographically stratified population RaceAge

16. June 27, 2005 Example Stratification HPV Age range 15-30 years Age range 15-30 years Stratify at 5 year intervals Stratify at 5 year intervals Different contact rates can be assigned to each group Different contact rates can be assigned to each group 15-1920-2425-29 1 2.5 8 1.25 9 3 9.5 3.5 1.5

17. June 27, 2005 Population Interaction Consider our HPV population example: 15-1920-2425-29 1 2.5 8 1.25 9 3 9.5 3.5 1.5 A contact can take place between an individual in a subgroup {demographic, sexual activity class} and an individual In the same subgroup In the same subgroupor In a different subgroup In a different subgroup

18. June 27, 2005 Population Interaction Example A 23 year old male in the moderate activity class will make 3 contacts per year This is an example of where the contacts could occur 15-1920-2425-29 1 2.5 8 1.25 9 3 9.5 3.5 1.5

19. June 27, 2005 So far... Sexual Activity Classes Sexual Activity Classes Demographic Stratification Demographic Stratification Transmission Dynamics Transmission Dynamics Contact RatesContact Rates Population InteractionPopulation Interaction

20. June 27, 2005 Population States Now, we need to keep track of Who is susceptible to the disease Who is susceptible to the disease Who has the disease and is infectious Who has the disease and is infectious Who has recovered from the disease Who has recovered from the disease Also for HPV Who has been Vaccinated Who has been Vaccinated Who has the disease and been vaccinated, Vaccinated Infectious Who has the disease and been vaccinated, Vaccinated Infectious

21. June 27, 2005 HPV Note: A constant population is maintained. Every year/update in the model a proportion of the population Enters or ages-in as susceptibles Enters or ages-in as susceptibles Leaves or ages-out Leaves or ages-out Total Sexually Active Population Recovered Susceptible Infectious Vaccinated Infectious

22. June 27, 2005 Application We have developed a computer application interface to this model, which simulates endemic prevalence of a disease Our goal is to bridge the gap between the mathematical epidemiologists and professionals in industry and public health officials

23. June 27, 2005 Application Interface Input parameters: Disease Disease Population Population Vaccine Vaccine Output: Populations in each state over length of simulation

24. June 27, 2005 HPV Application Demo The following parameters are used in this demo: Age range 15-30, 5 year group interval Age range 15-30, 5 year group interval Sexual activity classes of low, moderate and high Sexual activity classes of low, moderate and high Denton County, TX population data from the 2000 U.S. Census Denton County, TX population data from the 2000 U.S. Census 75% vaccine efficacy 75% vaccine efficacy 90% vaccine coverage 90% vaccine coverage Vaccine is effective for 10 years Vaccine is effective for 10 years

25. June 27, 2005 Application Start Page

26. June 27, 2005 Input Parameters

27. June 27, 2005 Population Parameters 15-1920-2425-29Total Males15,92317,10619,23752,266 Females15,57918,47819,19353,250 Denton County, 2000 U.S. Census Data

28. June 27, 2005 Vaccine Parameters

29. June 27, 2005 Application Output

30. June 27, 2005 Population Graph Output

31. June 27, 2005 Population Ratio Graph Output

32. June 27, 2005 HPV Experiments Vaccination Policy Male (M) Female (F) Hughes, Garnett and Anderson Model None M & F F High-risk M & F High-risk F Spread targeting M & F Spread targeting F 0.0380.0200.0300.0350.0370.0330.0360.0390.0200.0270.0370.0380.0350.036 Temporal Model None M & F F Ages 15-19 M & F Ages 15-19 F Ages 20-24 M & F Ages 20-24 F Ages 25-29 M & F Ages 25-29 F 0.0470.0140.0330.0250.0380.0290.0400.0380.0440.0500.0150.0250.0260.0330.0310.0360.0400.043 Proportion of population with sustained infection

33. June 27, 2005 Results Qualitative assessment: Denton County would have a larger benefit in starting vaccination at age (15-19) than vaccinating high-risk minorities

34. June 27, 2005 Related Material Our paper currently in review with the model description in the appendix: http://cerl.unt.edu/~corley/pub/corley.ieee.bibe.2005.pdf link to the web-application demo http://cerl.unt.edu/~corley/hpv http://cerl.unt.edu/~corley/hpvhttp://cerl.unt.edu/~corley/hpv

35. June 27, 2005 Conclusion Modeling these diseases with this application will maximize resource allocation and utilization in the community or population where it is most needed

36. June 27, 2005 References J. Hughes and G. Garnett and L. Koutsky. The Theoretical Population-Level Impact of a Prophylactic Human Papilloma Virus Vaccine. Epidemiology, 13(6):631–639, November 2002. N. Bailey. The Mathematical Theory of Epidemics. Hafner Publishing Company, NY, USA, 1957. R. Anderson and G. Garnett. Mathematical Models of the Transmission and Control of Sexually Transmitted Diseases. Sexually Transmitted Diseases, 27(10):636–643, November 2000. S. Goldie and M. Kohli and D. Grima. Projected Clinical Benefits and Cost-effectiveness of a Human Papillomavirus 16/18 Vaccine. National Cancer Institute, 96(8):604–615, April 2004. The Youth Risk Behaviour Website, Centers for Disease Control and Prevention, 2005. http://www.cdc.gov/HealthyYouth/yrbs M. Katz and J. Gerberding. Postexposure Treatment of People Exposed to the Human Immunodeficiency Virus through Sexual Contact or Injection-Drug Use. New England Journal of Medicine, 336:1097-1100, April 1997. Youth Risk Behaviour Surveillance: National College Health Risk Behaviour Survey, Centers for Disease Control and Prevention, 1995. D. Heymann and G. Rodier. Global Surveillance, National Surveillance, and SARS. Emerging Infectious Diseases, 10(2), February 2004. E. Allman and J. Rhodes. Mathematical Models in Biology: An Introduction. Cambridge University Press, 2004. G. Garnett and R. Anderson. Contact Tracing and the Estimation of Sexual Mixing Patterns: The Epidemiology of Gonococcal Infections. Sexually Transmitted Diseases, 20(4):181–191, July-August 1993. G. Sanders and A. Taira. Cost Effectiveness of a Potential Vaccine for Human Papillomavirus. Emerging Infectious Diseases, 9(1):37–48, January 2003. J. Aron. Mathematical Modelling: The Dynamics of Infection, chapter 6. Aspen Publishers, Gaithersburg, MD, 2000. Thank You!