HPV Testing for Cervical Cancer Screening Study
HPV Testing for Cervical Cancer Screening Study
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.
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.
Inclusion Criteria:

 Women from 25 to 65 years of age, registered with the Medical Services Plain in BC
 attending a collaborating healthcare provider for routine cervical screening in Metro
 Vancouver or Greater Victoria.

 Exclusion Criteria:

 1. pregnant

 2. history of invasive cervical cancer

 3. no cervix

 4. HIV positive or on immunosuppressive treatments

 5. unable or unwilling to give informed consent

 6. Treatment of moderate or greater dysplasia within last 5 years