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

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.