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

November 15, 2013 updated by: University of Washington

HIV-Associated DNA Hypermethylation in Cervical Cancer

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

1680

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Senegal
- - Dakar, Senegal, BP 5035
    - Centre Hospitalier Universite De Fann
  - Dakar, Senegal, BP 5126
    - Hôpital Aristide Le Dantec

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

All study participants will be African women presenting to the clinical sites in Dakar, Senegal. Subjects will be representative of ethnic and racial groups living in Senegal.

Description

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

EXCLUSION CRITERIA:

< 18 years of age
Pregnant at screening
Cervix not intact
not able to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of hypermethylated genes that are predictive of cervical intraepithelial neoplasia (CIN) grade 3 or invasive cervical cancer Time Frame: 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.	3 years
Assessment of the risk of developing CIN3 in relationship to human papillomavirus (HPV) persistence, HIV, and the presence or acquisition of candidate hypermethylated genes Time Frame: 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.	3 years
Identification of HIV-related factors associated with the presence or acquisition of specific hypermethylated genes Time Frame: 3 years	Identify HIV-related factors (CD4 counts, viral load, HAART) which might be associated with the presence or acquisition of specific hypermethylated genes.	3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator: Nancy B. Kiviat, MD, Harborview Injury Prevention and Research Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

November 1, 2012

Study Registration Dates

First Submitted

April 9, 2007

First Submitted That Met QC Criteria