Efficacy of addition of high-risk human papillomavirus (hrHPV) testing by Hybrid Capture II to conventional cytological screening for cervical cancer

ISRCTN	ISRCTN64621295
DOI	https://doi.org/10.1186/ISRCTN64621295
Secondary identifying numbers	NTR215; 2002/02WBO

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 19/12/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr M. Herreilers
Scientific

SALTRO
Mississippidreef 83
P.O. Box 9300
Utrecht
3565 CE
Netherlands

Phone	+31 (0)30 236 1136
Email	m.herreilers@saltro.nl

Study information

Study design	Randomised triple-blinded active controlled parallel group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title
Study acronym	VUSABOB
Study objectives	1. In this study, we expect to decrease the number of referrals and repeat smears by immediately referring those women who are positive for high-risk human papillomavirus (hrHPV) with mildly abnormal smears for colposcopically-directed biopsies. Thus, for the remaining women with BMD who have tested hrHPV negative, repeat smears will not be necessary. 2. Secondly, we expect to be able to narrowly define a risk group of women within the group with normal cytology, that has an increased risk for the development of high-grade lesions based on the presence of hrHPV in the smear. The hrHPV negative women with normal smears will be at a decreased risk for the development of high-grade lesions, and for them, the interval between screening smears could be increased (from an interval of 5 years, to an interval of 8 - 10 years).
Ethics approval(s)	Received from local medical ethics committee
Health condition(s) or problem(s) studied	Cervical intraepithelial neoplasia
Intervention	In the VUSABOB, the addition of a high-risk human papillomavirus (hrHPV) test, using the commercially available and FDA approved Hybrid Capture II test, to the regular cervical screening programme in order to improve detection of precursor lesions of cervical cancer is evaluated using a cohort study of women whose smears were consecutively screened at a single laboratory in The Netherlands. Within this cohort study, we nested an unblinded trial of women with mildly abnormal screening smears and repeat and referral recommendations were based on the presence or absence of high-risk human papillomavirus. Secondly, we nested a randomised trial of women with normal cytology whose hrHPV test results were triple blinded to participants, treating clinicians and study personnel, and advised all women with blinded test results to repeat cervical screening at earlier intervals than current screening guidelines in the Netherlands recommend in order to evaluate screening strategies for women with normal cytology and a positive hrHPV test.
Intervention type	Other
Primary outcome measure	The primary outcome measure of VUSABOB is the occurrence of histologically confirmed cervical intra-epithelial neoplasia grade 3 (CIN3) lesions or (micro-) invasive carcinoma of the cervix found during the follow-up of currently diagnosed abnormalties, i.e., within 2 years. For women whose cytology results either regress to normal (in the unblinded trial of women with mild cytological abnormalities) or who clear an infection with hrHPV without cytological abnormalities (in the blinded trial of women with normal cytology diagnoses), we assume that no precursor lesions of cervical cancer are present. They will not be referred for colposcopically-directed biopsies and therefore will not have a histological endpoint. This policy complies with regular cervical screening in The Netherlands.
Secondary outcome measures	As a secondary outcome measure, histologically confirmed cervical intra-epithelial neoplasia grade 2 will also be investigated, since current guidelines recommend ablative treatment for these lesions as well. Other secondary parameters obtained include progression and regression of cytology diagnoses, clearance and acquisition of hrHPV infections and the number of referrals for colposcopically-directed biopsies.
Overall study start date	01/10/2003
Completion date	01/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	25000
Key inclusion criteria	1. Women invited for the cervical cancer screening program (aged 30 - 60 years) 2. General practitioner affiliated with SALTRO laboratory
Key exclusion criteria	1. Not called for screening, i.e., ages under 30 years, or over 60 years 2. Follow-up of previous non-normal cytology within the current screening round of the program, i.e., abnormal cytology or lesion greater than or equal to CIN3 less than 2 years before inclusion 3. Current pregnancy 4.Status after extirpation of the uterus or amputation of the portio
Date of first enrolment	01/10/2003
Date of final enrolment	01/12/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

SALTRO

Utrecht
3565 CE
Netherlands

Sponsor information

SALTRO - Doctor Laboratory & Thrombosis Service (The Netherlands)
Hospital/treatment centre

P.O. Box 9300
Utrecht
3506 GH
Netherlands

Email	saltro@saltro.nl
Website	http://www.saltro.nl/default.aspx
"ROR"	https://ror.org/00q6h8f30

Funders

Funder type

Hospital/treatment centre

Vrije University Medical Centre (VUMC) (The Netherlands) - Department of Pathology

No information available

SALTRO - Doctor Laboratory & Thrombosis Service (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan