A Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)
18 Years
N/A
Female
Cervical Cancer
Trial Information
A Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)
For the past twenty years, large epidemiologic natural history studies have played a crucial
role in achieving our current understanding of cervical neoplasia. We now know that human
papillomavirus (HPV) infection is necessary but not sufficient cause of cervical cancer.
Cervical pathogenesis evolves as follows: normal 'yields' oncogenic HPV infection 'yields'
precancer 'yields' invasive cancer. The majority of women with oncogenic HPV infections will
not develop cancer, and most HPV infections, even those with associated cellular changes,
regress in 1-2 years, probably eradicated or controlled by cellular immune response.
Morevoer, while invasive cancer and precancer are histologically well-defined, the
histological classification of low-grade lesions, now better defined as HPV infection, is
very heterogeneous and poorly reproducible. Identifying women at highest risk for cancer
prior to neoplastic progression is therefore a challenge. At present, we are unable to
predict with any accuracy which HPV infections will progress and which are among the
majority that regress. Currently, cytologic, histologic, and to some extent, HPV DNA assays
are the basis for triage, treatment, and follow-up. While this approach has permitted
successful cervical cancer prevention efforts, millions of women are diagnosed each year
with HPV infections, and because of the inability to distinguish those who will progress
from those who will regress, many women are over-treated as a result. It is therefore of
etiologic interest and of public health benefit to develop a method for identifying the
HPV-infected women at risk for progressing to precancer and invasion. To develop an accurate
and reproducible division of precursor lesions (HPV infection and precancer) will require
gaining knowledge about the molecular distinctions at each progressive disease state. Our
goal is to therefore comprehensively assess biomarkers of risk for progressive cervical
neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest
risk of cervical cancer from those with benign infection. Specifically, we will initially
implement a cross-sectional study to develop a comprehensive list of potential risk
biomarkers by examining cervical tissues of women with normal, HPV infection, precancer, and
cancer. They will measure gene expression profiles to gain an accurate and comprehensive in
vivo picture of cervical neoplasia carcinogenesis. We propose to then validate the most
promising identified candidate biomarkers in a prospective design by assessing their
predictive values for key outcomes related to progression (HPV persistence, diagnosis of
precancer) or non-progression (HPV clearance).
Inclusion Criteria
- INCLUSION CRITERIA:
All women who are referred for cervical colposcopy to the University of Oklahoma will be
considered eligible for the study. These women will be categorized into four groups: (i)
cancer, (ii) precancer, (iii) HPV-infected, and (iv) normal. Cancers will be limited to
women diagnosed with early cancer (Stage 1-2) to minimize potential disease effects.
Precancers will be defined as women diagnosed histologically with cervical intraepithelial
neoplasia 3 (CIN3). This is a highly specific and well-reproduced diagnosis which
effectively represents carcinoma in situ. All women testing DNA positive for any of the 13
known oncogenic HPV types (HPV-infected), but not diagnosed with CIN3 or cancer (all
stages) will be placed in the HPV-positive group. This group will therefore encompass all
HPV-infected women diagnosed with either cervical intraepithelial neoplasia 1 (CIN1),
CIN2, low grade squamous intraepithelial lesion (LSIL), atypical squamous cells of
undetermined significance (ASCUS), atypical glandular cells of underdetermined
significance (AGUS), or found cytologically normal. Women referred to the colposcopy
clinic but found to be negative for oncogenic HPV and normal upon histological diagnoses
will be eligible as normal controls; this approach will be an ethical method for
collecting biopsies from essentially "normal" women as there are many benign "look alike"
conditions that are ruled out in colposcopy clinics. While this group may not be a random
sample of the general population, the use of specimens from these women as controls will
ensure a group of women who are truly confirmed as having no neoplasia.
EXCLUSION CRITERIA:
Women attending the clinic solely for vaginal colposcopies will be excluded from the
study. Women who are under 18 years of age or pregnant at the visit will also be excluded
from the study. In addition, women who have had prior treatment (women coming to the
clinic for a follow-up visit subsequent to treatment (women coming to the clinic for a
follow-up visit subsequent to treatment or women coming for their initial clinic visit
following pretreatment with chemotherapy or radiation) will be excluded. All women with
known HIV or AIDS will be excluded from the study. This information will not be readily
available unless the woman has previously been seen at the University of Oklahoma clinic.
This event is considered rare; recent studies of HIV and AIDS by the University of
Oklahoma from the same population have been terminated due to the lack of HIV/AIDS
detected in the population.
Type of Study:
Observational
Study Design:
N/A
Principal Investigator
Nicolas Wentzensen, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
999903302
NCT ID:
NCT00339989
Start Date:
September 2003
Completion Date:
Related Keywords:
- Cervical Cancer
- Molecular Markers
- Human Papillomavirus
- Cervix
- Cancer
- Microarray
- Uterine Cervical Neoplasms
Name | Location |
|---|---|
| University of Oklahoma | Oklahoma City, Oklahoma 73190 |
