Clinical trial NCT00479375: Randomized Controlled Trial of Human Papillomavirus Testing in Primary Cervical Cancer Screening
Official title: Randomized Controlled Trial of Human Papillomavirus Testing in Primary Cervical Screening
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Cancer
Cervical Intraepithelial Neoplasia
Keywords: screening
human papillomavirus
Lead sponsor: Skane University Hospital
Sponsor class: OTHER
Collaborators: name: Swedish Cancer Society
name: Europe Against Cancer (European Union Directorate General XII- Public Health)
First posted: 2007-05-28
Enrollment: 12527
Sex: FEMALE
Minimum age (years): 32
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief summary: Human papillomavirus (HPV)-based cervical screening is known to increase sensitivity for detection of high-grade cervical intraepithelial neoplasia (CIN). Randomized trials of longitudinal efficacy are required to assess whether these gains represent overdiagnosis or a protective effect.

Methods: A total of 12527 women, aged 32-38, attending population-based invitational screening in Sweden were randomized 1:1 to HPV test and cytology (intervention arm) or cytology only (control arm). HPV-positive women were invited for a second HPV test at least one year later and women with type-specific persistent infections were then invited to colposcopy. A similar number of random double-blinded procedures are performed in the control arm. Women are followed with comprehensive registry-based follow-up. Primary outcome is the relative rates of CIN grade 2 or worse (CIN2/CIN3+) found in subsequent screening. Secondary outcomes are the relative rates of CIN2/CIN3+ found in the aseline screening and outcomes stratified by grade of CIN (CIN 2 or CIN3+).


Eligibility criteria: Inclusion Criteria:

* Women aged 32-38 years old
* Attending the Swedish population-based organised cervical screening program

Exclusion Criteria:

* Not providing informed consent

Primary outcomes:
measure: Incidence of CIN2/CIN3+ lesions (which includes invasive cancers and in situ adenocarcinomas) found by subsequent screening (i.e. after the enrollment screening round and its associated follow-up).
timeFrame: On average 4 years post baseline
Secondary outcomes:
measure: Secondary outcomes were the incidence of CIN2/CIN3+ lesions at enrollment screening (including associated follow-up) and outcomes stratified by CIN2 and CIN3+ lesions as endpoints.
timeFrame: On average 4 years post baseline
measure: Re-analysis of primary and secondary outcomes also after subsequent 3-yearly screening rounds
timeFrame: On average 7, 10, 13 (et cetera) years post base-line
Other outcomes:
Locations:
city: Malmo
country: Sweden
facility: Malmo University Hospital
Study officials:
affiliation: Malmo University Hospital, Lund University
name: Joakim Dillner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Forslund O, Antonsson A, Edlund K, van den Brule AJ, Hansson BG, Meijer CJ, Ryd W, Rylander E, Strand A, Wadell G, Dillner J, Johansson B. Population-based type-specific prevalence of high-risk human papillomavirus infection in middle-aged Swedish women. J Med Virol. 2002 Apr;66(4):535-41. doi: 10.1002/jmv.2178.
citation: Elfgren K, Rylander E, Radberg T, Strander B, Strand A, Paajanen K, Sjoberg I, Ryd W, Silins I, Dillner J; Swedescreen Study Group. Colposcopic and histopathologic evaluation of women participating in population-based screening for human papillomavirus deoxyribonucleic acid persistence. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 1):650-7. doi: 10.1016/j.ajog.2005.01.056.
citation: Elfstrom KM, Smelov V, Johansson AL, Eklund C, Naucler P, Arnheim-Dahlstrom L, Dillner J. Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial. BMJ. 2014 Jan 16;348:g130. doi: 10.1136/bmj.g130.
citation: Naucler P, Ryd W, Tornberg S, Strand A, Wadell G, Elfgren K, Radberg T, Strander B, Johansson B, Forslund O, Hansson BG, Rylander E, Dillner J. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med. 2007 Oct 18;357(16):1589-97. doi: 10.1056/NEJMoa073204.