Comparison of Triage Strategies for HPV-Positive Women: Canadian Cervical Cancer Screening Trial Results

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 26; no. 6; pp. 923 - 929
• Main Authors: Isidean, Sandra D, Mayrand, Marie-Hélène, Ramanakumar, Agnihotram V, Rodrigues, Isabel, Ferenczy, Alex, Ratnam, Sam, Coutlée, François, Franco, Eduardo L
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 01-06-2017
• Subjects: Adult; Aged; Canada; Cancer screening; Cellular biology; Cervical cancer; Cervix; Colposcopy; Cytology; Female; Genotypes; Health risks; Human papillomavirus; Humans; Load distribution; Mass Screening - methods; Medical screening; Middle Aged; Papillomaviridae; Papillomaviridae - metabolism; Sensitivity; Squamous cells; Strategy; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - pathology; Widening
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.epi-16-0705

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.
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.
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.
Concerns surrounding HPV-based screening can be effectively mitigated via triage.
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.
.