title: Comparison of Triage Strategies for HPV-Positive Women: Canadian Cervical Cancer Screening Trial Results.
abstract: Background:High-risk human papillomavirus (HR-HPV) testing has become a preferred cervical cancer screening strategy in some countries due to its superior sensitivity over cytology-based methods for identifying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). Improved sensitivity has been accompanied by reductions in specificity and concerns regarding overscreening and overtreatment of women with transient or nonprogressing HR-HPV infections. Triage of HR-HPV+women to colposcopy is, thus, warranted for appropriate management and treatment.Methods:Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2+among HR-HPV+women (age, 30-69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18+triage were also evaluated.Results:A strategy referring all women HPV16/18+and HPV16/18-, but with atypical squamous cells of undetermined significance or worse cytology (ASC-US+) had the highest sensitivity [82.5%; 95% confidence interval (CI), 70.9%-91.0%] but yielded the highest colposcopy referral rate. HPV16/18+triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%-75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL+) triage yielded a low sensitivity (32.8%; 95% CI, 21.9%-45.4%) but had the most favorable specificity (93.6%; 95% CI, 91.0%-95.6%), positive predictive value (41.5%; 95% CI, 28.1%-55.9%), and colposcopy referral rate of strategies examined. HPV viral load triage strategies did not perform optimally overall. Inclusion of HR-HPV genotypes 31 and 52 to HPV16/18+triage provided the highest sensitivities.Conclusion:Concerns surrounding HPV-based screening can be effectively mitigated via triage.Impact:Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV+women may decide the success of its widening utilization.Cancer Epidemiol Biomarkers Prev; 26(6); 923-9. ©2017 AACR.
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Isidean
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada.|Départements d'Obstétrique-Gynécologie et de Médecine Sociale et Préventive, Université de Montréal et CRCHUM, Montréal, Québec, Canada.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Mayrand
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Agnihotram V
authors.initials: AV
authors.lastname: Ramanakumar
authors.affiliation: Département de Médecine Familiale, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Isabel
authors.initials: I
authors.lastname: Rodrigues
authors.affiliation: Department of Pathology, McGill University and Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.affiliation: Division of Community Health and Humanities, Memorial University, St. John's, Newfoundland and Labrador, Canada.
authors.forename: Sam
authors.initials: S
authors.lastname: Ratnam
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada.|Département de Microbiologie-Infectiologie, Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Coutlée
authors.affiliation: Division of Cancer Epidemiology, McGill University, Montreal, Quebec, Canada. eduardo.franco@mcgill.ca.
authors.forename: Eduardo L
authors.initials: EL
authors.lastname: Franco
mesh_terms: D000328:Adult; D000368:Aged; D002170:Canada; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D027383:Papillomaviridae / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology