The main objective is to determine whether testing for TSLC1 methylation in hrHPV positive women with abnormal cytology better predicts underlying high-grade cervical lesions necessitating ablative treatment.
ID
Source
Brief title
Condition
- Reproductive and genitourinary neoplasms gender unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the frequency of CIN3 in two study populations,
i.e. women who test positive for hrHPV and TSLC1 compared with women who test
negative for either or both hrHPV and TSLC1.
Secondary outcome
As one of the secondary parameters it will be assessed whether the CIN3 lesions
are advanced lesions. This will be evaluated by measuring the size of the
lesions using colposcopic imaging and the status of molecular markers for
advanced CIN3 (a.o. elevated hTERT mRNA expression levels) in the lesions.
Background summary
Infection with high-risk human papillomavirus (hr-HPV) is necessary for the
development of cervical cancer, but additional (epi)genetic processes drive
the progression of a hr-HPV-induced premalignant cervical intraepithelial
neoplasia (CIN, graded 1 to 3) to invasive cancer
Despite the population based cervical screening program still 750 women are
diagnosed with cervical cancer patients in The Netherlands each year. This can
in part be explained by a considerable degree of false-negativity of the
cytology, which is used for cervical screening.
In our previous studies we have shown that additional testing for hrHPV results
in a major improvement of the screening program, particularly due to a
reduction in false negative scrapes. Recently, we also showed that the
specificity of the detection of women at higest risk of invasive cancer can be
improved by testing for silencing of the TSLC1 gene, a gene which was also
shown to be functionally involved in cervical carcinogenesis(Steenbergen et
al., J.Nat.Cancer Inst. 2004).
We hypothesize that testing of cervical scrapes or other cervical specimens for
hrHPV and TSLC1 silencing improves the detection of women that are at highest
risk to develop invasive cervical cancers. This will lead to an improved
clinical management of women who are referred to the outpatient clinic for
abnormal cytology and reduce the overtreatment of women who are not at
immediate risk to develop invasive cervical cancer.
Study objective
The main objective is to determine whether testing for TSLC1 methylation in
hrHPV positive women with abnormal cytology better predicts underlying
high-grade cervical lesions necessitating ablative treatment.
Study design
open, prospective, intervention study
Intervention
Participating women will receive a user-friendly self-sampling package by
regular mail in order to collect a cervico-vaginal specimen. These specimens
will be send to the Vumc and tested for the presence of hr-HPV DNA and TSLC1
methylation.
When visiting the gynaecologist women will be examined by colposcopy as part of
the routine procedures.
Women who test positive for both hr-HPV and TSLC1 methylation will be directly
treated by large loop excision of the transformation zone (LLETZ) following
colposcopic examination, as is the regular procedure.
Women who test negative for either or both hrHPV and TSLC1 methylation will not
be treated directly but colposcopy-directed biopsies will be taken first for
histomorphological analysis. In this group of women the treatment/follow-up
strategy will be based on the colposcopic and histological outcome; i.e. women
with high gradeCIN lesions will be treated and those with less severe lesions
will undergo follow-up cytology and colposcopy at 6 months.
All procedures at the gynaecologist will be in accordance with current
treatment guidelines in the Netherlands.
Study burden and risks
The burden for participants is nearly equal to the burden of the regular visit
to the gynaecologist. The extra risks are negligible. The only extra burden
involves the self-sampling of cervical-vaginal cells using a user-friendly
self-sampling device.
No blood samples will be taken and no questionnaires or diaries have to be
filled in.
De Boelelaan 1117
1081 HV Amsterdam
Nederland
De Boelelaan 1117
1081 HV Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
-Female
-Age 20-70
-Previous two Pap smears read as bordeline/mild dyskaryosis (Pap2/3a1) or previous single Pap smear read as moderate dyskaryosis or worse (*Pap3a2)
-Intact cervix (no history of treatment involving damage to the transformation zone of the cervix)
- Sufficient knowledge of the Dutch language.
- Able to understand the content of the study (according to the gynecologist).
- Signed informed consent form.
Exclusion criteria
-Pap smear read as Pap 5 (suspect for invasive cancer)
-Cancer at other sites
-Withdrawal of permission by the patient
-History of surgery on the cervix
-Pregnancy or pregnant in the last 3 months.
-Breast-feeding, or breast-feeding in the last 3 months.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL13108.029.06 |