Abstract

<div>Abstract<p><b>Background:</b> 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<sup>+</sup>). 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<sup>+</sup> women to colposcopy is, thus, warranted for appropriate management and treatment.</p><p><b>Methods:</b> Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2<sup>+</sup> among HR-HPV<sup>+</sup> women (age, 30–69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18<sup>+</sup> triage were also evaluated.</p><p><b>Results:</b> A strategy referring all women HPV16/18<sup>+</sup> and HPV16/18<sup>−</sup>, but with atypical squamous cells of undetermined significance or worse cytology (ASC-US<sup>+</sup>) had the highest sensitivity [82.5%; 95% confidence interval (CI), 70.9%–91.0%] but yielded the highest colposcopy referral rate. HPV16/18<sup>+</sup> triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%–75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL<sup>+</sup>) 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<sup>+</sup> triage provided the highest sensitivities.</p><p><b>Conclusion:</b> Concerns surrounding HPV-based screening can be effectively mitigated via triage.</p><p><b>Impact:</b> Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV<sup>+</sup> women may decide the success of its widening utilization. <i>Cancer Epidemiol Biomarkers Prev; 26(6); 923–9. ©2017 AACR</i>.</p></div>

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