title: Human papillomavirus testing versus cytology in primary cervical cancer screening: End-of-study and extended follow-up results from the Canadian cervical cancer screening trial.
abstract: The Canadian Cervical Cancer Screening Trial was a randomized controlled trial comparing the performance of human papillomavirus (HPV) testing and Papanicolaou cytology to detect cervical intraepithelial neoplasia of grades 2 or worse (CIN2+) among women aged 30-69 years attending routine cervical cancer screening in Montreal and St. John's, Canada (n = 10,154). We examined screening and prognostic values of enrollment cytologic and HPV testing results. Extended follow-up data were available for St. John's participants (n = 5,754; 501,682.6 person-months). HPV testing detected more CIN2+ than cytology during protocol-defined (82.9 vs. 44.4%) and extended (54.2 vs. 19.3%) follow-up periods, respectively. Three-year risks ranged from 0.87% (95% CI: 0.37-2.05) for HPV-/Pap- women to 35.77% (95% CI: 25.88-48.04) for HPV+/Pap+ women. Genotype-specific risks ranged from 0.90% (95% CI: 0.40-2.01) to 43.84% (95% CI: 32.42-57.24) among HPV- and HPV16+ women, respectively, exceeding those associated with Pap+ or HPV+ results taken individually or jointly. Ten-year risks ranged from 1.15% (95% CI: 0.60-2.19) for HPV-/Pap- women to 26.05% (95% CI: 15.34-42.13) for HPV+/Pap+ women and genotype-specific risks ranged from 1.13% (95% CI: 0.59-2.14) to 32.78% (95% CI: 21.15-48.51) among women testing HPV- and HPV16+, respectively. Abnormal cytology stratified risks most meaningfully for HPV+ women. Primary HPV testing every 3 years provided a similar or greater level of reassurance against disease risks as currently recommended screening strategies. HPV-based cervical screening may allow for greater disease detection than cytology-based screening and permit safe extensions of screening intervals; genotype-specific testing could provide further improvement in the positive predictive value of such screening.
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, QC, Canada.
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Isidean
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, QC, Canada.|Départements d'Obstétrique-Gynécologie et de Médecine Sociale et Préventive, Université de Montréal et CRCHUM, Montréal, QC, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Mayrand
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, QC, Canada.
authors.forename: Agnihotram V
authors.initials: AV
authors.lastname: Ramanakumar
authors.affiliation: Newfoundland and Labrador Public Health Laboratory, St. John's, NL, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Gilbert
authors.affiliation: Newfoundland and Labrador Public Health Laboratory, St. John's, NL, Canada.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Reid
authors.affiliation: Département de Médecine Familiale, Université de Montréal, Montréal, QC, Canada.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodrigues
authors.affiliation: Department of Pathology, McGill University and Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.affiliation: Division of Community Health and Humanities, Memorial University, St. John's, NL, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Ratnam
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, QC, Canada.|Département de Microbiologie-Infectiologie, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Coutlée
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, QC, Canada. eduardo.franco@mcgill.ca.
authors.forename: Eduardo L
authors.identifier: http://orcid.org/0000-0002-4409-8084
authors.initials: EL
authors.lastname: Franco
mesh_terms: D000328:Adult; D000368:Aged; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D065006:Papanicolaou Test / Q000379:methods; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology / Q000821:virology
keywords: cervical cancer; cytology; genotyping; human papillomavirus; screening