Brief Title
Human Papillomavirus (HPV) and Risk of Cervical Precancer and Cancer
Official Title
The HPV Persistence and Progression (PaP) Cohort at Kaiser Permanente Northern California
Brief Summary
Background:
- In most women, HPV infection does not cause symptoms and the infection goes away on its
own. In a small percentage of women, the HPV infection does not go away and sometimes
can result in cervical precancer or cancer.
- There are several different types of HPV. A better understanding of which types are
related to cervical precancer and cancer may help guide doctors in clinical management
of women who test positive for HPV and better understand why some women develop disease
while others do not.
Objectives:
- To determine whether certain types of HPV are more risky than others and if so, whether
they warrant separate detection in screening for cervical precancer and cancer.
- To determine if lasting infection by different HPV types carry different risk of
cervical precancer and cancer.
- To determine what viral and genetic factors influence the development of cervical
precancer and cancer.
- To evaluate new HPV tests and new biomarkers of cervical cancer risk.
Eligibility:
-Women 30 years of age and older who are in the cervical cancer screening program at the
Kaiser Permanente health plan in Northern California. Women who tested positive for HPV and a
random sample of women who tested negative for the virus are included.
Design:
-Data about participants genetic background and the type of carcinogenic HPV with which they
are infected are analyzed.
Detailed Description
The carcinogenicity of the 15 HPV types with carcinogenic potential varies greatly. We wish
to clarify clinical utility of carcinogenic HPV DNA testing in women 21 and older by
understanding the unique properties of individual HPV genotypes for viral persistence and
progression. Specifically, we seek to understand the timing and determinants of viral
clearance versus persistence and, given persistence, the risk of progression to CIN3/cancer
(greater than or equal to CIN3) among women infected with each type of carcinogenic HPV
genotype at the ages when cancer occurs. The relevant natural history data are lacking. There
are no NCI or other cohorts in which these and other questions are being adequately
addressed.
Kaiser Permanente Northern California (KPNC) routinely uses a FDA-approved pooled-HPV
genotype DNA test for carcinogenic HPV (Hybrid Capture 2 [HC2], Qiagen Corporation,
Gaithersburg, MD) as an adjunct to cytology for cervical cancer screening in women 30 and
older and as a triage for immediate colposcopy for women with equivocal Pap results at all
ages. We are teaming with KPNC to create a carcinogenic HPV-positive cohort (HPV Persistence
and Progression Cohort or PaP Cohort) for investigating the natural history of HPV genotypes.
Specifically, we will store approximately 60,000 baseline specimens from the following
sub-populations: 1) approximately 40,000 HPV positives and a random population sample of
4,000 baseline specimens from women aged 30 years and older; 2) approximately 5,000
HPV-orcytology-positives and random population sample of 2,000 baseline specimens from women
aged 25-29 years of age; and 3) approximately 5,000 HPV-or cytology-positives and random
population sample of 2,000 baseline specimens from women aged 21-24 years of age. We will use
efficient sampling designs to achieve high power with minimal laboratory analyses, with
specimens selected for testing based on clinical outcomes ascertained by linkage to the
Kaiser cytology and histology databases and KPNC s active yearly follow-up of all
HC2-positive women. We plan to "follow" women for three years after their enrollment in
2007-8 by banking their residual specimens collected at their return visits; longer follow-up
would likely be biased by extensive censoring due to treatment.
Extremely low-cost specimen accrual, computerized follow-up using the KPNC databases, and
leveraged funding will make this cohort highly cost-effective, with a proposed budget of
$1,030,954 over 5 years. The de novo cost of screening this population to identify
approximately 50,000 HPV-positive women 21 and older, which is performed by KPNC as part of
routine screening and at no cost to us, is approximately $50 million. The clinical follow-up,
cytology, and histologic diagnoses cost millions more. We can obtain genotyping and variant
testing without cost to the Division of Cancer Epidemiology and Genetics (DCEG), via
collaborations and the aforementioned Cooperative Agreement. The major costs are for
personnel to save and handle the specimens, extraction of clinical and questionnaire data,
and to offer women whose specimens have been banked an opt-out for use of the specimens.
Study Type
Observational
Primary Outcome
CIN2+/CIN3+/Cancer
Secondary Outcome
HPV Clearance
Condition
Cervical Neoplasia
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
131110
Start Date
January 29, 2007
Completion Date
April 30, 2020
Primary Completion Date
April 1, 2020
Eligibility Criteria
- INCLUSION CRITERIA:
Women in KPNC aged 25 years or older who tested positive for HPV.
Will also include a random sample of women who tested negative for HPV.
EXCLUSION CRITERIA:
Male.
Children under 18.
Gender
Female
Ages
21 Years - 100 Years
Accepts Healthy Volunteers
No
Contacts
Mark H Schiffman, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00435214
Organization ID
999907079
Secondary IDs
07-C-N079
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Mark H Schiffman, M.D., Principal Investigator, National Cancer Institute (NCI)
Verification Date
April 2020