TABLE 2.
Univariate diagnostic accuracy for triage using cytology, HPV genotyping or S5 methylation for CIN3+, CIN2+ and CIN2 endpoints, among hrHPV positive women with abnormal cytology re‐weighted to represent all hrHPV positive biopsied women (n = 3797)
| Triage marker | Cytology | Genotyping | Methylation | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HSIL+ | AGC | ASC‐H | LSIL | ASC‐US | HPV16 positive | HPV18 positive | HPV16/18 positive | HPV31/33 positive | hrHPV other positive | S5 positive (≥0.8 cut‐off) | S5 positive (≥1.4 cut‐off) | |
| n positive | 287 | 117 | 379 | 1217 | 1797 | 913 | 159 | 1072 | 484 | 2241 | 1831 | 1393 |
| CIN3+ (n = 459) | ||||||||||||
| n | 157 | 17 | 113 | 45 | 127 | 247 | 25 | 272 | 72 | 115 | 382 | 357 |
| PPV (95% CI) | 54.94 (49.18, 60.70) | 14.34 (7.98, 20.70) | 29.79(25.18, 34.39) | 3.68(2.62, 4.73) | 7.05(5.87, 8.23) | 27.01(24.13, 29.89) | 15.87(10.18, 21.55) | 25.36(22.76, 27.97) | 14.91 (11.74, 18.08) | 5.11(4.20, 6.02) | 20.87(19.01, 22.73) | 25.63(23.33, 27.92) |
| NPV (95% CI) | 91.42 (90.49, 92.35) | 87.99(86.94, 89.04) | 89.89(88.88, 90.90) | 83.96(82.54, 85.37) | 83.40(81.77, 85.03) | 92.65(91.70, 93.60) | 88.09(87.03, 89.14) | 93.15(92.20, 94.09) | 88.34(87.24, 89.43) | 77.89(75.83, 79.95) | 96.11(95.26, 96.97) | 95.77(94.96, 96.57) |
| Sensitivity(95% CI) | 34.34(28.84, 39.83) | 3.65(0.25, 7.05) | 24.63(20.30, 28.97) | 9.76(8.09, 11.43) | 27.62(25.55, 29.69) | 53.78(50.55, 57.02) | 5.49(1.95, 9.04) | 59.28(56.33, 62.22) | 15.74(12.50, 18.99) | 24.98(23.19, 26.78) | 83.33(81.63, 85.04) | 77.82(75.63, 80.00) |
| Specificity(95% CI) | 96.13(93.90, 98.36) | 97.01(93.91, 100.00) | 92.02(89.30, 94.75) | 64.88(62.20, 67.56) | 49.96(47.65, 52.27) | 80.04(77.44, 82.63) | 96.00(92.95, 99.05) | 76.04(73.48, 78.59) | 87.66(84.73, 90.59) | 36.30(34.31, 38.30) | 56.59(54.32, 58.86) | 68.97(66.54, 71.40) |
| CIN2+ (n = 987) | ||||||||||||
| n | 256 | 24 | 209 | 186 | 312 | 410 | 58 | 468 | 167 | 352 | 709 | 618 |
| PPV (95% CI) | 89.14(85.53, 92.74) | 20.57(13.23, 27.90) | 55.16(50.15, 60.16) | 15.31(13.29, 17.33) | 17.35(15.60, 19.10) | 44.91(41.68, 48.13) | 36.45(28.96, 43.93) | 43.65(40.68, 46.62) | 34.41(30.18, 38.64) | 15.72(14.22, 17.23) | 38.71(36.48, 40.94) | 44.40(41.79, 47.01) |
| NPV (95% CI) | 79.16(77.82, 80.51) | 73.84(72.42, 75.26) | 77.25(75.84, 78.65) | 68.97(67.18, 70.75) | 66.24(64.17, 68.32) | 80.00(78.54, 81.46) | 74.46(73.05, 75.88) | 80.96(79.48, 82.43) | 75.24(73.77, 76.71) | 59.22(56.78, 61.66) | 85.86(84.32, 87.40) | 84.67(83.23, 86.11) |
| Sensitivity(95% CI) | 25.89(20.82, 30.96) | 2.43(0.00, 5.23) | 21.20(17.08, 25.31) | 18.88(16.68, 21.08) | 31.60(29.45, 33.75) | 41.55(38.35, 44.75) | 5.86(2.21, 9.52) | 47.41(44.42, 50.40) | 16.88(13.54, 20.22) | 35.71(33.72, 37.69) | 71.84(69.78, 73.90) | 62.65(60.11, 65.19) |
| Specificity(95% CI) | 98.89(97.68, 100.00) | 96.70(93.46, 99.94) | 93.95(91.55, 96.35) | 63.32(60.61, 66.02) | 47.14(44.83, 49.45) | 82.10(79.61, 84.58) | 96.41(93.51, 99.30) | 78.51(76.05, 80.97) | 88.70(85.88, 91.52) | 32.79(30.85, 34.74) | 60.06(57.82, 62.31) | 72.44(70.10, 74.79) |
| CIN2 a (n = 528) | ||||||||||||
| n | 98 | 7 | 96 | 142 | 185 | 163 | 33 | 196 | 94 | 238 | 327 | 261 |
| PPV (95% CI) | 75.89(68.51, 83.27) | 7.27(2.18, 12.36) | 36.13(30.36, 41.90) | 12.08(10.21, 13.94) | 11.08(9.58, 12.59) | 24.52(21.25, 27.78) | 24.46(17.17, 31.75) | 24.51(21.53, 27.49) | 22.91(18.86, 26.97) | 11.18(9.84, 12.52) | 22.55(20.40, 24.70) | 25.24(22.59, 27.88) |
| NPV (95% CI) | 86.59(85.41, 87.77) | 83.91(82.65, 85.18) | 85.94(84.71, 87.17) | 82.15(80.53, 83.76) | 79.43(77.49, 81.37) | 86.34(85.04, 87.65) | 84.54(83.28, 85.79) | 86.91(85.60, 88.22) | 85.17(83.89, 86.46) | 76.03(73.63, 78.44) | 89.33 87.94, 90.73) | 88.41(87.10, 89.72) |
| Sensitivity(95% CI) | 18.56(11.85, 25.26) | 1.37(0.00, 3.66) | 18.21(13.58, 22.85) | 26.80(24.27, 29.34) | 35.05(32.76, 37.34) | 30.93(27.42, 34.44) | 6.19(2.10, 10.27) | 37.11(33.77, 40.46) | 17.87(14.17, 21.57) | 45.02(42.90, 47.13) | 61.86(59.35, 64.36) | 49.48(46.44, 52.53) |
| Specificity(95% CI) | 98.89(97.09, 100.00) | 96.70(93.20, 100.00) | 93.95(91.08, 96.81) | 63.32(60.56, 66.08) | 47.14(44.75, 49.54) | 82.10(79.19, 85.01) | 96.41(93.25, 99.56) | 78.51(75.66, 81.35) | 88.70(85.64, 91.76) | 32.79(30.80, 34.79) | 60.06(57.54, 62.58) | 72.44(69.72, 75.16) |
Note: Data reweighted to biopsied population. Note that CIN2 is treated as a false positive for the CIN3+ analysis.
Abbreviations: ASC‐H, atypical squamous cells—cannot rule out HSIL; ASC‐US, atypical squamous cells of undetermined significance; CI, confidence interval; CIN2, cervical intraepithelial neoplasia grade 2 [CIN2] or greater [CIN2+]; CIN3, cervical intraepithelial neoplasia grade 3 [CIN3] or greater [CIN3+]; hrHPV, high‐risk human papillomavirus; HSIL, high‐grade squamous intraepithelial lesion or greater [HSIL+]; LSIL, low‐grade squamous intraepithelial lesion; NPV, negative predictive value; PPV, positive predictive value.
Denominator excludes CIN3+ women (n = 459).