Preliminary results from the Canadian Cervical Cancer Screening Trial (CCCaST Study)

E Duarte-Franco MD MPH^a,b, MH Mayrand MD MSc^c,d, F Coutl, Ã

^aDepartment of Oncology, ^bDepartment of Family Medicine, ^cDepartment of Epidemiology and Biostatistics; McGill University, Montreal, Montreal, ^dDepartment of Obstetrics and Gynecology, CHUM, Montreal, ^eDepartment of Microbiology and Immunology, Université de Montreal, St. John’s, Newfoundland, Canada, ^fNewfoundland Public Health Laboratory, St. John’s, Newfoundland, Canada, ^gDepartment of Family Medicine, Université de Montreal, Hamilton, Ontario, Canada, ^hDepartment of Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada, ⁱDepartment of Pathology, McGill University, Montreal, Quebec, Canada

AIM: To compare the efficacy of HPV testing and Pap cytology in a primary screening setting for cervical cancer and its high-grade precursors. METHODS: This randomized controlled trial is enrolling women 30-69 years of age in Montreal and St. John's, Canada, to undergo a screening protocol comparing HPV DNA testing via the Hybrid Capture 2 assay with the conventional Pap cytology. All participants receive both tests, but are randomized as to the order in which those tests are done. All women with an abnormality on the Pap smear at an 'atypical squamous cells of undetermined significance' (ASC-US) threshold or a positive HPV test undergo colposcopy and biopsy. A random 10% sample of participants with negative results by the index test in each arm also undergoes disease verification via the latter diagnostic methods. This strategy will enable us to derive estimates of sensitivity, specificity and positive and negative predictive values for each test with correction for verification bias. The statistical analysis will focus on the management results based on the index test in each arm. RESULTS: Nearly half of the target 12,000 study participants have been enrolled by mid-November 2003. All baseline demographic and medical characteristics are similarly distributed between the 2 study groups. 6% of women in each arm had a positive HPV test and 3% an abnormal Pap test. We will present preliminary estimates of the tests’ performance, using histologically confirmed high-grade intra-epithelial lesions and cancers as the gold-standard. CONCLUSIONS: The CCCaST study is one of the few randomized controlled trials of HPV testing in primary screening worldwide. It avoids most methodological limitations that have affected the interpretation of previous studies based on split-sample designs. This trial will provide much needed information on the relative efficacy and cost-effectiveness of HPV testing as the central component of a cervical cancer screening intervention.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 992 (Screening & detection).