80 Chapter 3 Revision diagnosis* No dysplasia CIN1 CIN2 CIN3 Cervical cancer Total Original diagnosis No dysplasia 55 23 1 1 0 80 CIN1 33 59 17 2 0 111 CIN2 16 17 14 11 0 58 CIN3 4 0 23 56 0 83 Cervical cancer 0 0 0 0 3 3 Total 108 99 55 70 3 335 *revision diagnosis based on morphologic features combined with the interpretation of the p16INK4A and Ki-67 immunostainings, except for n = 57 based on morphologic features only. Abbreviations: CIN1-3, cervical intraepithelial neoplasia grade 1-3 Supplementary Table 3.1 Original diagnosis versus revision diagnosis. SUPPLEMENTARY INFORMATION Sensitivity Specificity PPV NPV A Cytology n/N % 95% CI n/N % 95% CI % 95% CI % 95% CI CIN3+ 65/73 89.0% (81.9-96.2%) 382/609 62.7% (58.9-66.6%) 22.3% (17.5-27.0%) 97.9% (96.5-99.4%) CIN2+ 111/128 86.7% (80.0-92.6%) 373/554 67.3% (63.4-71.2%) 38.0% (32.4-43.6%) 95.6% (93.6-97.7%) B HPV16/18 genotyping CIN3+ 46/64 71.9% (60.9-82.9%) 369/555 66.5% (62.6-70.4%) 19.8% (14.7-25.0%) 95.3% (93.3-97.4%) CIN2+ 75/116 64.7% (56.0-73.4%) 346/503 68.8% (64.7-72.8%) 32.3% (26.3-38.3%) 89.4% (86.3-92.5%) C ASCL1/LHX8 methylation* CIN3+ 57/73 78.1% (68.6-87.6%) 455/609 74.7% (71.3-78.2%) 27.0% (21.0-33.0%) 96.6% (95.0-98.2%) CIN2+ 86/128 67.2% (59.1-75.3%) 429/554 77.4% (74.0-80.9%) 40.8% (34.1-47.4%) 91.1% (88.5-93.7%) D Cytology + HPV16/18 genotyping CIN3+ 61/64 95.3% (90.1-100.5%) 240/555 43.2% (39.1-47.4%) 16.2% (12.5-19.9%) 98.8% (97.4-100.2%) CIN2+ 109/116 94.0% (89.6-98.3%) 236/503 46.9% (42.6-51.3%) 29.0% (24.4-33.6%) 97.1% (95.0-99.2%) E ASCL1/LHX8 methylation* + HPV16/18 genotyping CIN3+ 57/64 89.1% (81.4-96.7%) 282/555 50.8% (46.7-55.0%) 17.3% (13.2-21.4%) 97.6% (95.8-99.4%) CIN2+ 96/116 82.8% (75.9-89.6%) 269/503 53.5% (49.1-57.8%) 29.1% (24.2-34.0%) 93.1% (90.2-96.0%) *using a predefined theshold (70% specificity) Abbreviations: CI, confidence interval; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; n, number of; N, group size; NPV, negative predicted value; PPV, positive predicted value Supplementary Table 3.2 Sensitivity and specificity of baseline cytology, genotyping and ASCL1/LHX8 methylation for detection of CIN3+ and CIN2+ – subgroup with revision diagnosis.
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