1. Susan Hariri, PhD Division of STD Prevention, CDC March 10, 2008
HPV Vaccine Impact Monitoring Project in the Emerging Infections Programs (EIP) Network
Susan Hariri, PhD
Division of STD Prevention, CDC
March 10, 2008

2. Objectives
To conduct population-based monitoring of HPV vaccine impact over the next 10 years
Monitor cervical cancer precursors
Cervical intraepithelial neoplasia (CIN 2/3)
Adenocarcinoma in situ (AIS)
Characterize HPV types associated with lesions
Determine vaccine history among cases
Monitor overall trends
Cervical cancer screening
Vaccine uptake
HPV-related disease
Detailed information
Frequency
40 types that are known to infect the genital tract
High and low risk based on oncogenic potential

3. Outcomes Incidence of CIN2, CIN3, and AIS diagnoses by vaccine status
HPV type distribution by vaccine status
Vaccine types 16, 18
Other high-risk types
Estimate CIN2, CIN3, and AIS disease burden
Probability of screening in population
Changes in screening practices and utilization

4. Cervical Intraepithelial Neoplasia
Histologic diagnosis (biopsy)
Spectrum of intraepithelial changes of cervix
Graded on basis of thickness of abnormality
Epithelial layer is divided into thirds

5. Why Monitor CIN and AIS?
Invasive cervical cancer is primary outcome of interest
Takes too long to develop
Lower incidence than CIN
CIN 2/3 and AIS are cancer precursors
AIS is in situ cancer of glandular lining
CIN 3 is Carcinoma in situ (CIS)
CIN 2 – may regress
Sometimes caused by low-risk HPV types
Can be histologically indistinguishable from CIN 3
Included in vaccine efficacy clinical trials
Used as threshold for treatment in US for added measure of safety
Allow more timely evaluation of vaccine impact

6. Model of vaccine impact on HPV 16/18-Related CIN 2/3 Incidence- females 12-85 years
Merck model
Assumptions: Linear increase in vaccine coverage from 0-70% within 5 years
Current US cervical cancer screening rates

7. Emerging Infections Programs (EIP) A population-based, scientific, public health network
Network of CDC and 11 state health departments
Local health departments, public health laboratories, clinical laboratories, infection control practitioners, healthcare providers, academic institutions, and other federal agencies
National public health resource, engaged in surveillance, prevention, and control of emerging infectious diseases and other activities that go beyond usual health department
Active surveillance
Applied epidemiology and laboratory research
Implementation and evaluation of pilot prevention and intervention projects
Flexible response
Working with collaborators
FDA, USDA, EPA, etc
Assess the public health impact of emerging infections and to evaluate methods for their prevention and control.
Addresses important issues
Undertakes well-suited activities
Maintains flexibility
Provides training
Develops and evaluates public health practice

8. EIP Sites

9. Centers of Hepatitis Surveillance Excellence
EIP Projects
Foodborne Diseases
Active Surveillance Network
FoodNet
EIP Influenza Projects –
- Adult Hospitalization Surveillance
- Pediatric Hospitalization Surveillance
- Influenza Vaccine Effectiveness Evaluation
UNEX
Unexplained Deaths and Critical Illness
Centers of Hepatitis Surveillance Excellence
Antibiotic
Resistance
Unexplained Encephalitis

10. Centers of Hepatitis Surveillance Excellence
EIP Projects
Foodborne Diseases
Active Surveillance Network
FoodNet
HPV VACCINE IMPACT MONITORING PROJECT
EIP Influenza Projects –
- Adult Hospitalization Surveillance
- Pediatric Hospitalization Surveillance
- Influenza Vaccine Effectiveness Evaluation
UNEX
Centers of Hepatitis Surveillance Excellence
Antibiotic
Resistance
Unexplained Encephalitis

11. HVIMP Partnerships State Health Departments: Academic Institutions:
California Department of Health Services
University of California, Berkeley
University of California, San Francisco
Colorado Dept. of Public Health & Environment
University of Colorado Health Sciences Ctr.
Connecticut Department of Public Health
Yale University
University of Connecticut
Georgia Department of Human Resources
Emory University
University of Georgia
Maryland Dept. of Mental Health and Hygiene
Johns Hopkins University
University of Maryland
Minnesota Department of Health
University of Minnesota
New Mexico Department of Health
University of New Mexico
New York State Department of Health
University of Rochester
Oregon Department of Human Services
Oregon Health Sciences University
Tennessee Department of Health
Vanderbilt University
Texas Department of State Health Services

12. HVIMP Sites

13. HVIMP Sites State Catchment area Total female population 18+
(2000 US census)
Expected annual
number of CIN 2/3 cases- 18+ TN
Davidson
County
232,454
540 NY
Monroe
289,131
570 CT
New Haven
329,766
640 CA
Alameda
554,625
1270

14. HVIMP Objectives
Develop comprehensive approach to monitoring HPV type-specific CIN 2/3 and AIS
Monitor incidence of CIN 2/3 and AIS over time
Characterize HPV types among subset of CIN 2/3 cases
Determine vaccine history among subset of CIN 2/3 cases
Implement plan in pilot project

15. HVIMP- Aim 1 Develop monitoring system
Identify partners and stakeholders
Enumerate data (and specimen) sources
Determine data management and reporting capacity
Determine human subjects/IRB issues
Including specimen collection and vaccine status
Identify sources of aggregate data
Cervical cancer screening rates in catchment
Develop a summary plan and review with CDC

16. HVIMP- Aim 2 Implement plan Demonstrate feasibility
Case finding
Reporting
Specimen collection
Vaccine history
Determine operational needs

17. Population health utilization, screening rates
HVIMP Process
Routine Screening
Cytology
HSIL
CIN 2/3
Histology
e-Report to surveillance system
PCR for HPV typing
Central pathology review
18-39 year olds
Population health utilization, screening rates
Basic CRF
Enhanced CRF
Vaccine history
Other detailed info

18. Basic Case Report Form Completed on all reported (eligible) cases
Data elements
Age
Race/ethnicity
Insurance status and type
Cervical biopsy information
Diagnosis
Procedure

19. Enhanced Case Report Form
Completed on random subset
Main purpose: to obtain vaccine history on subset of cases that will have HPV typing
Additional info
Cervical cancer screening history
Monitor screening frequency and patterns among cases
Other relevant medical history

20. Histopathologic Review and HPV Typing
Cases selected for enhanced monitoring
Histology specimens sent to CDC
Histopathology review by pathology panel
Standardize definition
HPV DNA typing
High-risk types

21. HVIMP Challenges Case ascertainment Vaccine history
Inconsistent nomenclature
Standardize algorithm
Vaccine history
Vaccine registries
Medical chart review
Patient interview
Electronic laboratory reporting
Adolescent vaccines are not covered in most areas
Providers may not routinely collect information
Time and resource intensive
Require information on pathology requisitions

22. HVIMP Timeline Phase 1 – planning Phase 2 - data collection
Phase 3 - specimen collection
2007
2008

23. HVIMP Next Steps Operationalize system in selected sites
Collect baseline data
Evaluate strengths and limitations
Add new sites
Evaluate HPV vaccine impact beyond 2 years
5 years
10 years

24. Acknowledgements California EIP Connecticut EIP New York EIP
Heidi Bauer
Ina Park
Erin Whitney
Connecticut EIP
Jim Hadler
Jim Meek
Linda Niccolai
Lyn Sosa
New York EIP
Nana Bennett
Ghinwa Dumyati
Christine Long
Tennessee EIP
Karen Bloch
Allen Craig
Bill Schaffner
CDC
Lauri Markowitz
Beth Unger
Bob Pinner
Suzanne Powell
Jim Braxton
Mona Saraiya
Eileen Dunne