Human Papillomavirus (HPV) and Risk of Cervical Precancer and Cancer
Condition: Cervical Neoplasia
MeSH terms: Neoplasms
Study type: Observational

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.
    

Observational model: Cohort
Time perspective: Other
Sampling method: Probability Sample
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.
      
Biospecimen description: 
      Discarded cervical Pap test specimens
    
Keywords: Cytology; papilloma virus; CIN; Screening; Cervix; Cervical Cancer