Identifying Genes That Predict Risk of Developing Cervical Intraepithelial Neoplasia or Invasive Cervical Cancer

Sponsor

University of Washington (Other)

Overall Status

Completed

CT.gov ID

NCT00458562

Collaborator

National Cancer Institute (NCI) (NIH)

1,680

Enrollment

Locations

Duration (Months)

840

Patients Per Site

10.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Finding certain changes in genes may help doctors predict which patients are at risk of developing cervical intraepithelial neoplasia or invasive cervical cancer and may help the study of cancer in the future.

PURPOSE: This clinical trial is studying genes that may predict which patients are at risk of developing cervical intraepithelial neoplasia or invasive cervical cancer.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer Precancerous Condition

Detailed Description

OBJECTIVES:

Utilize molecular assays to identify a panel of hypermethylated genes that are predictive of cervical intraepithelial neoplasia (CIN) grade 3 or invasive cervical cancer (ICC) among patients with or without HIV infection.
Perform a nested case-control study assessing the risk of developing CIN3 in relationship to human papillomavirus (HPV) persistence, HIV, and the presence or acquisition of candidate hypermethylated genes in these patients.
Identify HIV-related factors (e.g., CD4 counts, viral load, and highly active antiretroviral therapy [HAART]) that might be associated with the presence or acquisition of specific hypermethylated genes in these patients.

OUTLINE: This is a longitudinal, multicenter study.

Patients undergo biopsy for removal of cervical tissue. Patients also undergo blood and urine sample collection. Samples are analyzed for the presence of cancer or changes that indicate that cancer might develop. Patients also undergo colposcopy at baseline and at 3 years.

After completion of study procedures, patients are followed every 4 months for up to 3 years.

PROJECTED ACCRUAL: A total of 1,150 patients will be accrued for this study.

Study Design

Study Type:

Observational

Actual Enrollment :

1680 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

HIV-Associated DNA Hypermethylation in Cervical Cancer

Study Start Date :

Jan 1, 2006

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
HIV+, <CIN2 HIV positive women without CIN2-3 or worse
HIV-, no >=CIN3 biopsy, HR HPV+ HIV negative women without biopsy-proven CIN3 or worse, and with high risk HPV infection
HIV-, <=CIN1, HPV- at screening HIV negative women who are <= CIN1 and HPV negative at screening

Outcome Measures

Primary Outcome Measures

Identification of hypermethylated genes that are predictive of cervical intraepithelial neoplasia (CIN) grade 3 or invasive cervical cancer [3 years]
Use molecular assays to identify a panel of hypermethylated genes that are predictive of CIN-3/ICC among women with and without HIV infection. We will rank genes by their ability to discriminate normal cervical tissue from CIN-3/ICC after stratifying by HIV infection.
Assessment of the risk of developing CIN3 in relationship to human papillomavirus (HPV) persistence, HIV, and the presence or acquisition of candidate hypermethylated genes [3 years]
Perform a nested case control study assessing the risk of developing CIN-3 in relationship to HPV persistence, HIV, and the presence or acquisition of the candidate hypermethylated genes.
Identification of HIV-related factors associated with the presence or acquisition of specific hypermethylated genes [3 years]
Identify HIV-related factors (CD4 counts, viral load, HAART) which might be associated with the presence or acquisition of specific hypermethylated genes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

Underwent Pap smear, human papillomavirus (HPV) testing, and HIV testing AND meets any of the following criteria:
Biopsy and colposcopy confirmed cervical intraepithelial neoplasia (CIN) or invasive cervical cancer (ICC), meeting any of the following criteria:
CIN grade 2-3 or higher
Repeated CIN1 (times 6)
Abnormal Pap smear (atypical squamous cells of undetermined significance [ASCUS] or worse)
HIV seropositive
Negative cytology but positive for high-risk human papillomavirus (HPV)
Negative cytology and negative HPV
HIV negative (without biopsy-proven CIN 3 or worse) and high-risk HPV infection (types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 55, 56, 58, 59, 68, 82, 83, 73)
= 18 years of age
Intact cervix
Not pregnant
Able to provide informed consent