A randomized controlled trial of Human Papillomavirus (HPV) testing for cervicalcancer screening: trial design and preliminary results (HPV FOCAL Trial)

Abstract

BackgroundIn the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC) triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome.Methods/DesignHPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive casesDiscussionTo date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5%) were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%). In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%). Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program.Trial RegistrationInternational Standard Randomised Controlled Trial Number Register, ISRCTN79347302

Long‐term HPV type‐specific risks of high‐grade cervical intraepithelial lesions: A 14‐year follow‐up of a randomized primary HPV screening trial

“…Several studies have investigated the clinical relevance of testing for HPV in cervical screening programs, in Europe [29][30][31][32][33][34] and North America. 35,36 These studies as well as our study have shown strikingly concordant results regarding the extremely high predictive values of HPV testing. Only some of these studies have performed HPV genotyping, however.…”

Epidemiological study of high‑risk human papillomavirus infection in subjects with abnormal cytological findings in cervical cancer screening

“…Therefore, follow-up visits are important for women in the peri-menopausal period. A previous study demonstrated that with the polarization of cervical pre-cancerous lesions regarding the incidence age of cervical cancer, attention should be paid to women around the age of 30 years and those after the age of 50 years (35). Follow-up visits should be increased for HPV-positive patients.…”

The Road Ahead for Cervical Cancer Prevention and Control

“…That approach would also provide cytotechnicians with a smaller case load having a higher lesion prevalence (that is, a higher signal-to-noise ratio) and an overall more rewarding reviewing experience 17,18,26 . To evaluate that approach, a randomized controlled trial (the hpv focal trial) currently underway in British Columbia is comparing triage using hpv testing followed by lbc (Pap) with triage using lbc followed by hpv dna testing 27 . Results from focal, other similar comparative trials 28 , and demonstration projects (implementing hpv testing alone as the primary screening test) will be useful when the time comes once again to update screening guidelines.…”