134 Chapter 6 87.0-95.3%), with a colposcopy referral rate of 6.7% (95% CI 3.2-10.2%). Strategy VII, encompassing HPV16/18 genotyping AND ASCL1/LHX8 methylation, presents a slightly reduced PPV for CIN3+ of 33.3% (95% CI 14.5-52.2%), while maintaining a comparable NPV of 91.8% (95% CI 87.6-95.9%), along with a relatively low colposcopy referral rate of 12.4% (95% CI 7.7-17.0%). Similarly, FAM19A4/miR124-2 methylation (strategy I) exhibits a PPV of 32.1% (95% CI 14.8-49.4%) and an NPV of 92.2% (95% CI 88.1-96.3%), with a corresponding colposcopy referral rate of 14.4% (95% CI 9.5-19.4%). For strategy XI, involving HPV16/18/31/33/45 extended genotyping AND ASCL1/LHX8 methylation, the PPV diminishes further to 27.0% (95% CI 12.7-41.3%), while the NPV slightly increases to 92.4% (95% CI 88.2-96.5%), necessitating 19.1% (95% CI 13.5-24.6%) of colposcopy referrals. ASCL1/LHX8 methylation (strategy II) shows a PPV for CIN3+ of 24.6% (95% CI 13.4-35.7%) and an NPV of 94.2% (95% CI 90.2-98.1%), accompanied by a colposcopy PPV NPV Colposcopy referrals Triage strategy % 95% CI % 95% CI % 95% CI I FAM19A4/miR124-2 methylation 48.1% (29.3-67.0%) 76.6% (70.2-83.1%) 13.9% (9.0-18.8%) II ASCL1/LHX8 methylation 42.1% (29.3-54.9%) 79.6% (72.8-86.3%) 29.4% (23.0-35.8%) III HPV16/18 genotyping 36.6% (25.4-47.8%) 78.9% (71.6-86.1%) 36.6% (29.8-43.4%) IV HPV16/18/31/33/45 genotyping 30.5% (21.7-39.3%) 77.5% (68.9-86.2%) 54.1% (47.1-61.1%) V HPV16/18 genotyping AND FAM19A4/miR124-2 methylation 60.0% (29.6-90.4%) 75.0% (68.7-81.3%) 5.2% (2.0-8.3%) VI HPV16/18 genotyping OR FAM19A4/miR124-2 methylation 38.2% (28.1-48.3%) 82.9% (75.6-90.1%) 45.9% (38.9-52.9%) VII HPV16/18 genotyping AND ASCL1/LHX8 methylation 45.8% (25.9-65.8%) 75.9% (69.5-82.3%) 12.4% (7.7-17.0%) VIII HPV16/18 genotyping OR ASCL1/LHX8 methylation 37.5% (28.2-46.8%) 85.6% (78.3-92.8%) 53.6% (46.6-60.6%) IX HPV16/18/31/33/45 genotyping AND FAM19A4/ miR124-2 methylation 53.8% (26.7-80.9%) 75.1% (68.8-81.4%) 6.7% (3.2-10.2%) X HPV16/18/31/33/45 genotyping OR FAM19A4/ miR124-2 methylation 32.5% (24.1-40.9%) 82.4% (73.8-91.1%) 61.9% (55.0-68.7%) XI HPV16/18/31/33/45 genotyping AND ASCL1/LHX8 methylation 37.8% (22.2-53.5%) 75.8% (69.1-82.5%) 19.1% (13.5-24.6%) XII HPV16/18/31/33/45 genotyping OR ASCL1/LHX8 methylation 33.6% (25.3-41.9%) 85.5% (77.2-93.8%) 64.4% (57.7-71.2%) Table 6.1B Positive predictive value (PPV), negative predictive value (NPV) and direct colposcopy referral rates for CIN2+ of single and combined triage strategies in hrHPV-positive women with ASCUS/LSIL cytology. Non-dominant strategies are depicted in bold. Abbreviations: PPV, positive predictive value; NPV, negative predictive value; CIN2+, cervical intraepithelial neoplasia grade 2 or worse; CI, confidence interval; hr, high-risk; HPV, human papillomavirus; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade intraepithelial lesion
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