HPV Testing for Cervical Cancer Screening Study
Condition: Cervical Cancer Screening
MeSH terms: Uterine Cervical Neoplasms
Study type: Interventional

Summary: 
      This is a randomised controlled trial of HPV testing with cytology triage for HPV positive
      women compared to liquid-based cervical cytology (LBC). Although LBC is not widely used for
      cervical cancer screening in Canada at present, the Pan-Canadian Cervical Cancer Forum has
      recommended its use and as it is likely to be the standard of care by the time these data are
      published, the trial has been designed to account for this. Further, LBC will improve the
      cost-effectiveness of HPV testing because the LBC medium is suitable for both HPV testing as
      well as cytology and thereby allows the triage testing to be undertaken from the same sample
      without having to recall the women.
    

Detailed description: 
      There is now an overwhelming body of data to show that HPV testing has the potential to
      improve the effectiveness of cervical cancer screening programs and thereby reduce rates of
      cervical cancer. As a result, there is a growing ethical dilemma in that we potentially have
      the means to prevent disease and death among Canadian women, and yet the studies that have
      been undertaken do not offer the standard of evidence that is required to change large-scale
      public health programs such as cervical cancer screening. In recognition of this, the
      Pan-Canadian Cervical Cancer Forum (PCCCF) has called for the evaluation of HPV testing
      within the context of a Canadian organised cervical cancer screening program. Given the
      potential health benefits that could be achieved, and that a pan-Canadian expert group has
      issued a consensus statement calling for the evaluation of HPV testing for primary screening,
      it is now an imperative that a properly designed and powered study be conducted to
      definitively establish whether it will provide the hypothesised health benefits within
      Canada.

      The results of this trial will demonstrate whether or not the use of HPV testing as a single
      primary screening test within an organised Canadian cervical cancer screening program will be
      able to 1) provide further reductions in cervical cancer incidence, 2) allow the screening
      interval to be extended and 3) improve the cost-effectiveness of cervical cancer screening.
      If this trial demonstrates that HPV testing will provide these benefits, the BCCA will
      implement HPV testing as a single primary screening test within the provincial cervical
      cancer screening program and the trial will directly influence the provision of this service
      in BC. In addition, many other Canadian provinces and territories are either implementing or
      have plans to implement screening programs similar to the one in BC and by the time this
      trial is completed, many will have these programs operating. Therefore, the results of this
      trial will be directly applicable to these programs and constitute a demonstration project
      for the rest of Canada.

      A list of women who are due for cervical screening will be sent to study collaborating Family
      Physicians (FPs) each month from the study centre in the provincial screening program. An
      invitation letter will be sent by the FP to potentially eligible women due for cervical
      cancer screening. If women are interested in participating, they will contact the study
      centre for more information. Study staff discuss the details of the trial with them, confirm
      eligibility and administer a short survey. Women who consent to the trial will visit the FP
      for their screening test and samples will be obtained and sent to the BC Central Laboratory
      Service (BC-CLS) where it will be randomized into one of the study arms:

      Note: Recruitment to the safety arm was complete December 31, 2010 and from that point
      forward, women randomized 1:1 into the control or intervention arms only. A total of ~25,000
      women (~9140 each in the Control and Intervention arms respectively, and ~6,000 in the Safety
      arm) will be enrolled in the FOCAL trial.

      Control arm:

      Sample tested with LBC.

        -  Those with negative results will be recalled for next screen at 2 years and if negative
           again, for the exit screen at 4 years. Those with positive cytology results have reflex
           HPV testing, or referral to colposcopy based on results.

        -  Exit screen testing is both HPV and cytology testing

           2-year safety-check arm: Sample tested for HPV.

        -  HPV negatives recalled at 2-years for the exit screen with cytology

        -  Women who are HPV positive will have their residual LBC specimen processed for cytology
           and be managed according to the same protocol as HPV-positive women in the 4-year
           intervention arm.

           4-year intervention arm: Sample tested for HPV.

        -  HPV negatives will be recalled at 4 years for their exit screen with HPV and cytology
           testing

        -  Women who are HPV positive will undergo reflex cytology testing and those cytology
           negative will be recalled at 12 months for HPV testing and cytology. At 12 mos,
           participants will be referred to colposcopy if > or =ASC-US or HPV positive. If HPV and
           cytology negative at 12 months returned to the routine screening pool for this arm and
           recalled for the exit screen at 4-years.

        -  Women who are HPV positive and > or = ASC-US will be referred to colposcopy and managed
           according to colposcopy results.
    

Intervention name(s): Cervical cancer screening undertaken by HPV testing as a single primary screening test with cytology triage of women who are HPV positive; Cervical cancer screening undertaken by HPV testing as a single primary screening test with cytology triage of women who are HPV positive
Intervention type(s): Procedure; Procedure
Intervention description(s): See Detailed Description.; See detailed description.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: HPV Screening/Testing for cervical cancer screening