Condition category
Cancer
Date applied
20/04/2007
Date assigned
20/04/2007
Last edited
01/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.bccancer.bc.ca/hpvfocal/

Contact information

Type

Scientific

Primary contact

Dr Andrew J Coldman

ORCID ID

Contact details

BC Cancer Agency
8th floor
686 W Broadway
Vancouver
V5Z 1G1
Canada
+1 (0)604 877 6143
acoldman@bccancer.bc.ca

Type

Public

Additional contact

Dr Laurie Smith

ORCID ID

Contact details

BC Cancer Agency
711-750 West Broadway
Vancouver
V5Z 1H6
Canada
+1 (0)604 877 6098 ext. 4829
lsmith3@bccancer.bc.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MCT-82072

Study information

Scientific title

A multicentre randomised controlled parallel group evaluation of Human PapillomaVirus testing for cervical cancer screening

Acronym

HPV FOCAL

Study hypothesis

1. Establish efficacy of human papillomavirus (HPV) testing as stand alone screening test with cytology triage of HPV positive women
2. Establish an appropriate screening interval for HPV negative women
3. Determine cost-effectiveness of HPV testing as a primary screening test

Ethics approval

Research Ethics Board of the University of British Columbia-British Columbia Cancer Agency, 03/04/2007, ref: H06-04032

Study design

Multicentre three-arm randomised parallel-trial on diagnostic strategy with data analyst blinding

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Can be found at http://www.bccancer.bc.ca/hpvfocal

Condition

Human papillomavirus (HPV), cervical cancer

Intervention

1. HPV testing two-year safety check arm - liquid based cytology (LBC) sample tested only for HPV:
Those who are HPV negative will be screened again in two years for their exit screen, only with cytology so the results correlate with women in the control arm. Those who are HPV positive on the initial screening test will be managed the same way as HPV positive women in the four-year intervention arm.

2. HPV testing four-year intervention arm - 24. a.2.d. experimental intervention dose, duration, etc - LBC sample will only be tested for HPV:
HPV negatives will have their exit screen at four years (or earlier if deemed by Data Safety and Monitoring Committee) when they will be screened with HPV and cytology testing and those positive on either test referred for Colposcopy. HPV positive on their initial screen will have the residual of that specimen analysed with cytology.
a. If cytology negative they will be recalled at six month intervals for HPV/cytology testing and referred for colposcopy if greater than or equal to abnormal squamous cells of undertermined significance (ASCUS-US) at any recall or persistently HPV positive after three recalls
b. If cytology is greater than or equal to ASCUS-US they will be immediately referred for colposcopy and managed according to those results.

Amended as of 19/03/2009:
3. Control Arm - Conventional cytology with liquid based cytology -
On the basis of this result women will be managed as follows:
Within normal limits (negative results): Recalled for their next routine screen at 2 years, where the sample will undergo cytology testing. If negative again at the 2 year screen, recalled, for the exit screen at 4 years. At the 4 year exit screen, the sample obtained will undergo both HPV and cytology testing with those positive on either test being referred for colposcopy and then treated based on the colposcopy results.
ASC-H or greater than LSIL: (at recruitment visit or at the 2 year screen) will receive immediate colposcopy and treated based on the colposcopy results.
ASC-US: (at recruitment visit or at the 2 year screen) the residual of the specimen collected will undergo HPV testing. Follow-up based on the result of the HPV test:
a. HPV-positive: referred for immediate colposcopy and treated based on the colposcopy results
b. HPV-negative: recalled for repeat cytology testing in 12 months. If greater than or equal to ASC-US, referred for colposcopy and treated based on the colposcopy results. If cytology negative they will be returned to the routine screening pool for this arm.

Initial information at time of registration:
3. Control Arm - Conventional cytology with liquid based cytology - 24. b.1.cd. control intervention dose, duration, etc:
Liquid based cytology sample processed for cytology and followed according to existing provincial guidelines. Recalled again at two years for their second routine screen and at four years for their exit screen where they will be screened with cytology and HPV testing.

Added 10/01/2011:
Recruitment to the safety arm will terminate December 31, 2010 and from that point forward, women will be randomized 1:1 into the cytology or intervention arms only. A total of ~28,000 women (11,000 each in the Control and Intervention arms respectively, and ~6,000 in the Safety arm) will be enrolled in the FOCAL trial.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

1. Histologically confirmed cervical intraepithelial neoplasia (CIN) greater than or equal to grade two detected at two years in both the control and safety-check arms
2. CIN grade three (CIN3) or greater detected over the four years post recruitment in the control and intervention arms evaluated and compared as a surrogate marker for estimating reductions in incidence of cervical cancer, measured at four years
3. Detection of histologically confirmed greater than or equal to CIN3 in the participants allocated to six month re-testing, measured at two years
4. Total estimated cost per woman screened and total estimated cost per quality-adjusted life-year gained for each technology, measured at four years

Secondary outcome measures

Clearance of HPV infection in women who are HPV positive at recruitment, measured at two and four years.

Overall trial start date

01/08/2007

Overall trial end date

31/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Current information as of 04/11/2008:
1. Women aged 25 to 65 years
2. Registered with MSP
3. Attending a collaborating BC healthcare provider for regular cervical cancer screening (pap tests)

Initial information at time of registration:
1. Women aged 25 to 65 years
2. British Columbia residents
3. Eligible for routine cervical screening

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

~28,000

Participant exclusion criteria

Current information as of 01/12/2009 (effective 25/11/2009):
1. Pap smear less than one year ago
2. Pregnant (at time of initial sample)
3. History of moderate to severe cervical intraepithelial neoplasia (greater than CIN2) requiring treatment less than 5 years ago
4. History of invasive cervical cancer at any time
5. Complete hysterectomy with cervix removal
6. Human immunodeficiency virus (HIV) positive or receiving immunosuppressive treatments
7. Unable or unwilling to sign the Information and Consent form

Information as of 04/11/2008:
1. Pap smear less than one year ago
2. Pregnant
3. History of moderate to severe cervical intraepithelial neoplasia (greater than CIN2) requiring treatment less than 5 years ago
4. History of cervical cancer at any time
5. Complete hysterectomy with cervix removal
6. Human immunodeficiency virus (HIV) positive or receiving immunosuppressive treatments
7. Received HPV vaccination
8. Unable or unwilling to sign the Information and Consent form

Initial information at time of registration:
1. Pregnant
2. History of cervical cancer
3. Hysterectomy
4. Human immunodeficiency virus (HIV) positive
5. Unable to give informed consent

Recruitment start date

01/08/2007

Recruitment end date

31/12/2014

Locations

Countries of recruitment

Canada

Trial participating centre

BC Cancer Agency
Vancouver
V5Z 1G1
Canada

Sponsor information

Organisation

Provincial Health Services Authority (Canada)

Sponsor details

Finance Department
Suite 260
1770 West 7th Avenue
Vancouver
British Columbia
V6J 4Y6
Canada

Sponsor type

Government

Website

http://www.phsa.ca/default.htm

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (ref: MCT-82072)

Alternative name(s)

Instituts de Recherche en Santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Canada

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 preliminary results in http://www.ncbi.nlm.nih.gov/pubmed/20334685
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26674353

Publication citations

  1. Preliminary results

    Ogilvie GS, van Niekerk DJ, Krajden M, Martin RE, Ehlen TG, Ceballos K, Peacock SJ, Smith LW, Kan L, Cook DA, Mei W, Stuart GC, Franco EL, Coldman AJ, A randomized controlled trial of Human Papillomavirus (HPV) testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial)., BMC Cancer, 2010, 10, 111, doi: 10.1186/1471-2407-10-111.

  2. Results

    Cook DA, Mei W, Smith LW, van Niekerk DJ, Ceballos K, Franco EL, Coldman AJ, Ogilvie GS, Krajden M, Comparison of the Roche cobas® 4800 and Digene Hybrid Capture® 2 HPV tests for primary cervical cancer screening in the HPV FOCAL trial, BMC Cancer, 2015 , 15, 968, doi: 10.1186/s12885-015-1959-5.

Additional files

Editorial Notes

01/09/2016: Publication reference added. 10/01/2011: the target number of participants was changed from 33,000 to ~28,000.