Discovery of biomarkers for cervical neoplasia by genome-wide gene-expression profiling

Cervical cancer ranks fourth among cancers in women worldwide and is also the
fourth leading cause of cancer death in women worldwide. Invasive cervical
cancer is preceded by a state of cervical intraepithelial neoplasia (CIN). The
introduction of population-based cervical cancer screening is known to decrease
cancer incidence and mortality by early detection, followed by treatment of CIN
lesions.

Screening and triage-options are a Papanicolaou (Pap) smear, based on cytologic
sampling of the cervix, and high-risk human papillomavirus (HPV) testing. To
further reduce morbidity and mortality associated with cervical neoplasia,
novel strategies are needed to both identify and effectively treat CIN lesions
before they progress to cancer.

The tumorigenesis of cervical cancer is thought to be a complex process and
involves multiple genetic alterations(3). Only little is known about the
genomic differences between a normal cervix, intraepithelial disease and
invasive carcinoma. Gene expression profiling is a powerful tool to identify
and target markers associated with disease or therapy(4). RNA-based global
analyses of gene expression on have led to the identification of large numbers
of dysregulated genes in many different types of human cancers. However, there
have been relatively few reports in cervical cancers(3).

Previous research shows that the stability of the RNA for gene expression
profiles is achievable by using cervical material that is *snap frozen* in
liquid nitrogen straight after removal. Therefore we would like to start this
pilot-study with collecting *snap-frozen* tissue samples to compare the
genome-wide expression-profiles of small groups of different CIN samples,
cervical cancer and normal cervical tissue. When this pilot-study shows that
certain genes show potential as biomarkers for CIN or cervical cancer, a future
validation study with larger numbers of samples would be interesting.

To identify molecular alterations associated with cervical tumorigenesis, that
could be used as biomarker for improving detection and differentiation between
cervical cancer, cervical intraepithelial neoplasia and normal cervical tissue.

The study will be a prospective single-centre study. Patients will be included
from 01-01-2014 on until the required numbers for the pilot-study are reached.
This is expected to be in april 2017 .

Although study subjects will not benefit personally from participating, the
results of this study could prove valuable for all future patients with
suspected cervical neoplasia and cervical cancer. As stated earlier, the
pathologist specialised in gynaecology has stated that collection of the stated
tissue does not interfere with the pathologic evaluation. In group 1, the
biopsy will be taken after the planned removal of the cervix. Therefore there
is no additional risk for the women. In group 2 the biopsy will also be taken
after the LEEP tissue is removed. Therefore there is no additional risk for the
women. In group 3 an additional biopsy will be taken after the diagnostic
biopsies. The extra risk of bleeding or infection because of one additional
biopsy is very low.