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 over-screening and over-treatment of women with transient or non-progressing 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 HPV16/18+ and HPV16/18- but ASC-US+ women had the highest sensitivity (82.5%; 95% 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). LSIL+ cytology 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.
- Received September 8, 2016.
- Revision received December 14, 2016.
- Accepted January 7, 2017.
- Copyright ©2017, American Association for Cancer Research.