The primary objective of this study is to validate prospectively that testing for the DNA methylation status of some tumor suppressor genes predicts (non-)regression of a CIN2/3 lesion, and therefore can lead to prevention of overtreatment.
ID
Source
Brief title
Condition
- Other condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Health condition
cervicale intraepitheliale neoplasie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study endpoint is (non-)regression at the end of the study based on
histology of the cervical exit biopsy. Regression is defined as *CIN1 on the
exit biopsy based on morphology. Non-regression is defined as CIN2 or worse
(CIN2+) on the exit biopsy based on morphology.
Secondary outcome
The secondary study endpoint is defined as HPV clearance (double negative hrHPV
test at two consecutive time points).
Background summary
Current cytology-based cervical screening programs serve to detect and treat
high-grade precursor lesions (CIN2/3) to prevent cervical cancer. However, the
diagnostic*treatment trajectory is associated with considerable overtreatment
since CIN2/3 lesions have a high spontaneous regression rate. Pathologists are
unable to differentiate between CIN2/3 lesions with a low short-term
progression risk to cervical cancer (productive lesions), not in need of
immediate treatment, and those with a high short-term progression risk
(transforming lesions) that need immediate treatment. Recently, it has been
shown that DNA methylation markers can differentiate between productive and
transforming CIN2/3.
Study objective
The primary objective of this study is to validate prospectively that testing
for the DNA methylation status of some tumor suppressor genes predicts
(non-)regression of a CIN2/3 lesion, and therefore can lead to prevention of
overtreatment.
Study design
This study is designed as an observational longitudinal study with a follow-up
of 24 months.
Intervention
Standard therapy for CIN2/3 lesions consists of excision of the lesion by
either LLETZ or cold knife conisation. In this study, treatment consists of a
watchful waiting policy. Participants will be monitored by an intense follow-up
schedule consisting of 6-monthly visits to the colposcopy clinic for 2 years.
During these visits, cervical cytology, hrHPV testing, methylation marker
analysis and colposcopic evaluation of the cervix will be performed.
Study burden and risks
The main risk associated with participation in this study is the risk for
lesion progression. We consider the risk of cancer within the two year period
of close surveillance negligibly low since the median time from onset of CIN2/3
lesions to onset of cervical cancer is 23.5 years (95% CI: 20.8-26.6), and
estimated progression rates to cancer are 1.6% within 10 years, and 12% within
20 years following onset of CIN2/3. Moreover, the treatment indication for
lesions showing clinical progression (to >50% of the cervix in this study) is
more stringent than was used in an earlier prospective non-intervention study
(with threshold >75% of the cervix) that has been safely conducted by our group
in the past (Nobbenhuis et al., Lancet 1999). Close surveillance by regular
colposcopic evaluation of the lesion by a gynaecologist and, cytological and
molecular evaluation of cervical cells will minimize this risk and the risk of
missing a severe lesion. In case a lesion progresses into cervical cancer
during the study period, this will most likely be an early stage lesion that
can be treated by conisation with a very high success rate.The risk of
malignant transformation of CIN2/3 lesions is 1.6% within 10 years.
De Boelelaan 1117
Amsterdam 1081 HZ
NL
De Boelelaan 1117
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in the investigational treatment group of this study, a subject must meet all of the following criteria:
- CIN2 or CIN3 on a cervical punch biopsy
- CIN covering * 50% of the visible cervix
- Non-pregnant female aged 18-55 years
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- History of cervical pathology
- Transformation zone is not visible at colposcopy
- Prenatal diethylstilboestrol exposure
- Concomitant cancer
- Insufficient Dutch or English language skills;In case a subject falls pregnant during the study period she will not be excluded from participation. Her follow-up will not include self-sampling with the Evalyn Brush. Otherwise, follow-up will not be adjusted.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL56187.029.16 |
| OMON | NL-OMON29301 |