Randomized controlled trial of human papillomavirus testing versus Pap cytology in the primary screening for cervical cancer precursors: design, methods and preliminary accrual results of the Canadian cervical cancer screening trial (CCCaST).
Since infection with oncogenic human papillomavirus (HPV) has been considered a necessary cause of cervical cancer, tests for oncogenic HPV types have been proposed as adjuncts or replacements to Pap cytology. We designed the Canadian Cervical Cancer Screening Trial (CCCaST) to compare the relative efficacy of HPV DNA testing and Pap cytology in primary screening for cervical cancer and its high-grade precursors. CCCaST randomized women aged 30-69 years in Montreal (Quebec) and in St. John's (Newfoundland) to 1 of 2 screening groups: focus on Pap (conventional) or focus on HPV testing (Hybrid Capture 2). Women in both arms received both tests, but were randomized as to their order, the first test being the index test. Women with an abnormal Pap test or a positive HPV test underwent colposcopy and biopsy, as did a random sample of women with a negative index test. CCCaST enrolled 9,667 women between October 2002 and October 2004. At enrolment, 2.8% had an abnormal Pap test, 6.1% had a positive HPV test and 1.1% were abnormal in both tests. ASC-US was the most frequent cytological abnormality, representing 64% of abnormal Pap results. The frequency of abnormal Pap and HPV results decreased with increasing age and the proportion of HPV-positive results increased with the severity of Pap abnormality. Efficacy analysis will determine if the extra referrals with HPV DNA testing will translate into a relevant increase in high-grade cervical cancer precursor detection. Because of its design, CCCaST will provide sound evidence for formulating cervical cancer screening strategies.
Division of Cancer Epidemiology, Department of Oncology, McGill University, and Département de Microbiologie-Infectiologie, Hôpital Notre-Dame du Centre Hospitalier Universitaire de l'Université de Montréal, QC, Canada.
Marie-Hélène
MH
Mayrand
Eliane
E
Duarte-Franco
François
F
Coutlée
Isabel
I
Rodrigues
Stephen D
SD
Walter
Sam
S
Ratnam
Eduardo L
EL
Franco
D000328:Adult; D000368:Aged; D002170:Canada; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000821:virology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000821:virology; D015203:Reproducibility of Results; D012107:Research Design; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000821:virology; D014626:Vaginal Smears