Cervical NeoplasiaNCT00435214
Human Papillomavirus (HPV) and Risk of Cervical Precancer and Cancer
An observational study of Cervical Neoplasia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 100 years, women only
- Conditions the study is for
- Cervical Neoplasia
- How many people
- 131,110 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jan 2007to 30 Apr 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: We are teaming with Kaiser Permanente Northern California (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-or-cytologypositives 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.
Who may be able to join
- 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.
Who cannot join
- Male.
- Children under 18.
Trial locations and contacts
1 site in 1 country.
United States1 site
Kaiser Permanente Northern California
Oakland, California, 94612
About this study
Official title: The HPV Persistence and Progression (PaP) Cohort at Kaiser Permanente Northern California
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.
Read more
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.
Read the 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.
- Conditions
- Cervical Neoplasia
- Keywords
- Cytology, papilloma virus, CIN, Screening, Cervix, Cervical Cancer
- Medical subject headings
- Uterine Cervical Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
CIN2+/CIN3+/Cancer
Cervical histopathology; The detection of CIN2+,CIN3+, or cancer in histology results from tissue collected during cervical biopsies, excisional treatment or surgery.
Measured: Ongoing
Secondary outcomes (1)
HPV Clearance
HPV DNA testing:A negative HPV test result or normal cytology during follow-up visits.
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2007 (estimated)
- Study start29 Jan 2007
- Primary completion1 Apr 2020
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cervical NeoplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 131,110 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark H Schiffman, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00435214
- Sponsor's protocol ID
- 999907079
- Other IDs
- 07-C-N079
- Status last verified
- Apr 2020
- First submitted
- 13 Feb 2007
- Last updated
- 1 May 2020
- Results posted
- No
Publications
Gage JC, Sadorra M, Lamere BJ, Kail R, Aldrich C, Kinney W, Fetterman B, Lorey T, Schiffman M, Castle PE; PaP Cohort Study Group. Comparison of the cobas Human Papillomavirus (HPV) test with the hybrid capture 2 and linear array HPV DNA tests. J Clin Microbiol. 2012 Jan;50(1):61-5. doi: 10.1128/JCM.05989-11. Epub 2011 Nov 9.
PubMed 22075592Wentzensen N, Sun C, Ghosh A, Kinney W, Mirabello L, Wacholder S, Shaber R, LaMere B, Clarke M, Lorincz AT, Castle PE, Schiffman M, Burk RD. Methylation of HPV18, HPV31, and HPV45 genomes and cervical intraepithelial neoplasia grade 3. J Natl Cancer Inst. 2012 Nov 21;104(22):1738-49. doi: 10.1093/jnci/djs425. Epub 2012 Oct 23.
PubMed 23093560Lamere BJ, Castle PE, Fetterman B, Poitras N, Stanley M, Shieh J, Lorey T, Kinney W, Schiffman M. A study of borderline positive Hybrid Capture 2 tests in the Kaiser Permanente Northern California cervical screening program: evidence against retesting. J Virol Methods. 2013 Apr;189(1):77-9. doi: 10.1016/j.jviromet.2013.01.011. Epub 2013 Feb 4. No abstract available.
PubMed 23384678
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The HPV Persistence and Progression (PaP) Cohort at Kaiser Permanente Northern California
- ClinicalTrials.gov ID
- NCT00435214
- Acronym / sponsor ID
- 999907079
- Conditions
- Cervical Neoplasia
- Keywords
- Cytology, papilloma virus, CIN, Screening, Cervix, Cervical Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 131,110 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 29 Jan 2007 (actual)
- Primary completion
- 1 Apr 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 14 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Ages
- 21 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We are teaming with Kaiser Permanente Northern California (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-or-cytologypositives 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (2 listed)
- Male.
- Children under 18.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
CIN2+/CIN3+/Cancer
Time frame: Ongoing
Cervical histopathology; The detection of CIN2+,CIN3+, or cancer in histology results from tissue collected during cervical biopsies, excisional treatment or surgery.
1 secondary outcome
HPV Clearance
Time frame: Ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2020.
- Background: PubMed 22075592Gage JC, Sadorra M, Lamere BJ, Kail R, Aldrich C, Kinney W, Fetterman B, Lorey T, Schiffman M, Castle PE; PaP Cohort Study Group. Comparison of the cobas Human Papillomavirus (HPV) test with the hybrid capture 2 and linear array HPV DNA tests. J Clin Microbiol. 2012 Jan;50(1):61-5. doi: 10.1128/JCM.05989-11. Epub 2011 Nov 9.
- Background: PubMed 23093560Wentzensen N, Sun C, Ghosh A, Kinney W, Mirabello L, Wacholder S, Shaber R, LaMere B, Clarke M, Lorincz AT, Castle PE, Schiffman M, Burk RD. Methylation of HPV18, HPV31, and HPV45 genomes and cervical intraepithelial neoplasia grade 3. J Natl Cancer Inst. 2012 Nov 21;104(22):1738-49. doi: 10.1093/jnci/djs425. Epub 2012 Oct 23.
- Background: PubMed 23384678Lamere BJ, Castle PE, Fetterman B, Poitras N, Stanley M, Shieh J, Lorey T, Kinney W, Schiffman M. A study of borderline positive Hybrid Capture 2 tests in the Kaiser Permanente Northern California cervical screening program: evidence against retesting. J Virol Methods. 2013 Apr;189(1):77-9. doi: 10.1016/j.jviromet.2013.01.011. Epub 2013 Feb 4. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark H Schiffman, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cervical Neoplasia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CIN2+/CIN3+/Cancer (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00435214, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2020.