Low-Cost Molecular Cervical Cancer Screening Study
Condition: DNA Probes; E6 Protein; Uterine Cervical Neoplasms; HPV
MeSH terms: Uterine Cervical Neoplasms
Study type: Observational

Summary: 
      Background:

      - Low-cost molecular human papillomavirus (HPV) testing may offer a more robust alternative
      to Pap smears and visual inspection for cervical cancer screening of underserved women. Two
      low-cost molecular tests for human HPV, the HPV E6 Test and the careHPV test, have been
      developed to detect cervical cancer by testing for HPV DNA. These tests take between 2 and 3
      hours to run and may provide point-of-care (diagnostic testing at or near the site of patient
      care) testing for HPV. Researchers are interested in evaluating both tests to determine the
      best strategy for HPV testing of women who live in rural or underserved areas that have a
      high prevalence of cervical cancer diagnoses.

      Objectives:

        -  To evaluate the clinical performance of the HPV E6 Test and careHPV in detecting
           cervical cancer and precancerous lesions.

        -  To evaluate the best low-cost test or combination of tests for women who have been
           referred for cervical cancer screening or treatment.

        -  To compare the clinical performance of self-collected specimens versus
           clinician-collected specimens in detecting cervical cancer and precancerous lesions.

      Eligibility:

      - Women between 25 and 65 years of age who live in rural China.

      Design:

        -  This study involves an initial testing visit and a 1-year followup visit for a high-risk
           subgroup.

        -  Participants will have the HPV E6 test, careHPV, and a visual inspection test for
           cervical cancer. For comparison, participants will also have the standard HPV test
           approved by the U.S. Food and Drug Administration.

        -  Participants who test positive for HPV on any of the above tests will also have
           colposcopy to collect samples of cervical tissue for further study.

        -  A random sample of women who test negative for HPV will also have colposcopy.
           Participants may also have biopsies if there is visual evidence of cervical
           abnormalities.

        -  At the 1-year followup visit, participants in the high-risk subgroup will have the same
           tests as in the previous visit..
    

Detailed description: 
      Low-cost, molecular human papillomavirus (HPV) testing may offer a more robust alternative to
      Pap smears and visual inspection with acetic acid (VIA) for cervical cancer screening of
      underserved women. Two low-cost molecular tests for human papillomavirus (HPV) have been
      developed: 1) AVantage HPV E6 Test (Arbor Vita Corporation, Sunnyvale, CA, USA) ( HPV E6 Test
      ) detects E6 oncoproteins from HPV16, 18, and 45 and 2) careHPV (Qiagen, Gaithersburg, MD,
      USA) detects the DNA for a pool of 14 carcinogenic HPV genotypes. The HPV E6 Test will be
      ready for the first clinical evaluations in 2010. The HPV E6 Test works like an ELISA in
      strip format such that it takes less than two hours to run and may provide point-of-care
      (diagnostic testing at or near the site of patient care) testing. careHPV, a batch HPV DNA
      test that takes 2.5 hours to perform, has already been developed and is currently being used
      in demonstration projects. The results to date for careHPV are promising. As our primary
      objective, we wish to evaluate both tests, and to evaluate the best low-cost triage
      strategies for careHPV-positive results in areas of high prevalence of carcinogenic HPV DNA.
      A study of 7,500 women, ages 25-65 years, identified from an age- and region-stratified
      sample of women living in rural China will be conducted. All women will be screened at
      enrollment, and a high-risk subgroup at the one-year follow-up, by the following tests: HPV
      E6 Test, careHPV, and visual inspection with acetic acid (VIA). Women will also be screened
      at enrollment, and a high-risk subgroup at the one-year follow-up, using the digene HC2 HPV
      DNA Test TM ( HC2 ) (formerly known as Hybrid Capture 2)(Qiagen), the first U.S. Food and
      Drug Administration-approved HPV test and the gold standard for clinical HPV testing. At both
      time points, all screen-positive women will be evaluated by colposcopy using a rigorous
      diagnostic protocol. A random sample of screen negatives will undergo colposcopy but will
      only undergo biopsies if there is visual evidence of cervical epithelial abnormalities.
      careHPV-positive specimens will be tested for most carcinogenic HPV genotypes, HPV16, HPV18,
      and HPV45 using careHPV16/18/45. This triage test utilizes the same test platform as careHPV
      but screens only for those 3 carcinogenic HPV genotypes. The primary goals are 1) to evaluate
      the clinical performance of careHPV, the HPV E6 Test, and VIA for detection of cervical
      precancer and cancer and 2) to determine the positive predictive values of VIA, the HPV E6
      Test, and HPV16/18/45 detection by careHPV16/18/45 for cervical precancer and cancer among
      careHPV-positive women.
    

Time perspective: Prospective
Keywords: Cervical Cancer; Human Papilloma Virus (HPV); Cervical Intraepithelial Neoplasia (CIN)