Clinical trial NCT00458562: Identifying Genes That Predict Risk of Developing Cervical Intraepithelial Neoplasia or Invasive Cervical Cancer
Official title: HIV-Associated DNA Hypermethylation in Cervical Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cervical Cancer
Precancerous Condition
Keywords: cervical cancer
atypical squamous cells of undetermined significance
stage 0 cervical cancer
cervical intraepithelial neoplasia grade 1
cervical intraepithelial neoplasia grade 2
cervical intraepithelial neoplasia grade 3
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-11
Enrollment: 1680
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Identification of hypermethylated genes that are predictive of cervical intraepithelial neoplasia (CIN) grade 3 or invasive cervical cancer
timeFrame: 3 years
measure: Assessment of the risk of developing CIN3 in relationship to human papillomavirus (HPV) persistence, HIV, and the presence or acquisition of candidate hypermethylated genes
timeFrame: 3 years
measure: Identification of HIV-related factors associated with the presence or acquisition of specific hypermethylated genes
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Dakar
country: Senegal
facility: Centre Hospitalier Universite De Fann
city: Dakar
country: Senegal
facility: Hopital Aristide Le Dantec
Study officials:
affiliation: Harborview Injury Prevention and Research Center
name: Nancy B. Kiviat, MD
role: PRINCIPAL_INVESTIGATOR
References: