Low-Cost Molecular Cervical Cancer Screening Study
Low-Cost Molecular Cervical Cancer Screening Study
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..
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.
-  INCLUSION CRITERIA:

 1. have not been previously diagnosed with cervical cancer

 2. have a cervix

 3. are not pregnant

 4. are physically able to undergo routine cervical cancer screening 5) are able to
 provide informed consent

 -  We will not exclude women if they have had previous cervical cancer screening because
 we assume that even if a few women have been screened for cervical cancer, the quality
 of cytology screening was very poor.

 EXCLUSION CRITERIA:

 1) are not married AND report never having had sexual intercourse 2) have had a total
 hysterectomy

 3) have a history of cervical cancer

 4) are physically or mentally unable to undergo routine cervical cancer screening or unable
 to provide informed consent.

 5) are pregnant or have been pregnant in the last month

 -Women who are currently menstruating at the time of enrollment will be deferred from
 participating, and will become eligible to participate 7-14 days after menstruation has
 ended. The menstruating women will be advised to return for the screening 7 to 14 days
 after their menstrual period has concluded.