Triage strategies and colposcopy referrals in HPV-positive women with low-grade cytology 133 6 105 (54.1%) women tested positive for HPV16/18/31/33/45. Table 6.1 presents the positive predictive value (PPV) and negative predictive value (NPV) for all single and combined triage strategies for detecting CIN3+ and CIN2+. Triage strategies are highlighted in bold if there is no other strategy with equal or higher values for both PPV and NPV. The strategies presented exhibit strong heterogeneity in terms of the colposcopy referral rate. Starting with the most conservative strategy, HPV16/18 genotyping AND FAM19A4/miR124-2 methylation (strategy V) demonstrates a PPV for CIN3+ of 50.0% (95% CI 19.0-81.0%) and an NPV of 90.8% (95% CI 86.6-94.9%), with the lowest colposcopy referral rate of 5.2% (95% CI 2.0-8.3%). Similarly, another conservative strategy, HPV16/18/31/33/45 genotyping AND FAM19A4/miR124-2 methylation (strategy IX), achieves a PPV for CIN3+ of 46.2% (95% CI 19.1-73.3%) and NPV of 91.2% (95% CI PPV NPV Colposcopy referrals Triage strategy % 95% CI % 95% CI % 95% CI I FAM19A4/miR124-2 methylation 32.1% (14.8-49.4%) 92.2% (88.1-96.3%) 14.4% (9.5-19.4%) II ASCL1/LHX8 methylation 24.6% (13.4-35.7%) 94.2% (90.2-98.1%) 29.4% (23.0-35.8%) III HPV16/18 genotyping 18.3% (9.3-27.3%) 92.7% (88.1-97.3%) 36.6% (29.8-43.8%) IV HPV16/18/31/33/45 genotyping 14.3% (7.6-21.0%) 92.1% (86.5-97.7%) 54.1% (47.1-61.1%) V HPV16/18 genotyping AND FAM19A4/miR124-2 methylation 50.0% (19.0-81.0%) 90.8% (86.6-94.9%) 5.2% (2.0-8.3%) VI HPV16/18 genotyping OR FAM19A4/miR124-2 methylation 19.1% (10.9-27.3%) 95.2% (91.2-99.3%) 45.9% (38.9-52.9%) VII HPV16/18 genotyping AND ASCL1/LHX8 methylation 33.3% (14.5-52.2%) 91.8% (87.6-95.9%) 12.4% (7.7-17.0%) VIII HPV16/18 genotyping OR ASCL1/LHX8 methylation 18.3% (10.8-25.7%) 96.7% (93.0-100.4%) 53.6% (46.6-60.6%) IX HPV16/18/31/33/45 genotyping AND FAM19A4/ miR124-2 methylation 46.2% (19.1-73.3%) 91.2% (87.0-95.3%) 6.7% (3.2-10.2%) X HPV16/18/31/33/45 genotyping OR FAM19A4/ miR124-2 methylation 14.9% (8.5-21.2%) 94.5% (89.3-99.7%) 62.4% (55.6-69.2%) XI HPV16/18/31/33/45 genotyping AND ASCL1/ LHX8 methylation 27.0% (12.7-41.3%) 92.4% (88.2-96.5%) 19.1% (13.5-24.6%) XII HPV16/18/31/33/45 genotyping OR ASCL1/LHX8 methylation 15.2% (8.9-21.5%) 95.7% (90.8-100.5%) 64.4% (57.7-71.2%) Table 6.1A Positive predictive value (PPV), negative predictive value (NPV) and direct colposcopy referral rates for CIN3+ 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; CIN3+, cervical intraepithelial neoplasia grade 3 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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