TABLE 2.
Sensitivity and specificity of ASCL1/LHX8 methylation and HPV16/18 genotyping for detection of CIN3+ and CIN2+, stratified by cytology class
| Sensitivity | Specificity | PPV | NPV | Relative risk | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n/N | % | 95% CI | n/N | % | 95% CI | % | 95% CI | % | 95% CI | 95% CI | |||
| (A) ASCL1/LHX8 methylation a | |||||||||||||
| CIN3+ | NILM | 5/10 | 50.0% | (19.0‐81.0%) | 298/389 | 76.6% | (72.4‐80.8%) | 5.2% | (0.8‐9.7%) | 98.3% | (96.9‐99.8%) | 3.15 | (0.93‐10.67%) |
| Low‐grade cytology | 14/22 | 63.6% | (43.5‐83.7%) | 145/193 | 75.1% | (69.0‐81.2%) | 22.6% | (12.2‐33.0%) | 94.8% | (91.2‐98.3%) | 4.32 | (1.91‐9.78%) | |
| High‐grade cytology | 51/59 | 86.4% | (77.7‐95.2%) | 22/42 | 52.5% | (37.3‐67.5%) | 71.8% | (61.4‐82.3%) | 73.3% | (57.5‐89.2%) | 2.69 | (1.46‐4.96%) | |
| CIN2+ | NILM | 9/25 | 36.0% | (17.2‐54.8%) | 287/374 | 76.7% | (72.5‐81.0%) | 9.4% | (3.5‐15.2%) | 94.7% | (92.2‐97.2%) | 1.78 | (0.81‐3.87%) |
| Low‐grade cytology | 25/55 | 45.5% | (32.3‐58.6%) | 123/160 | 76.9% | (70.3‐83.4%) | 40.3% | (28.1‐52.5%) | 80.4% | (74.1‐86.7% | 2.06 | (1.32‐3.20%) | |
| High‐grade cytology | 63/83 | 75.9% | (66.7‐85.1%) | 10/18 | 55.6% | (32.6‐78.5%) | 88.7% | (81.4‐96.1%) | 33.3% | (16.5‐50.2%) | 1.33 | (1.01‐1.74%) | |
| (B) HPV16/18 genotyping | |||||||||||||
| CIN3+ | NILM | 8/10 | 80.0% | (55.2‐104.8%) | 247/354 | 69.8% | (65.0‐74.6%) | 7.0% | (2.3‐11.6%) | 99.2% | (98.1‐100.3%) | 8.66 | (1.87‐40.14%) |
| Low‐grade cytology | 13/22 | 59.1% | (38.5‐79.6%) | 117/176 | 66.5% | (59.5‐73.5%) | 18.1% | (9.2‐26.9%) | 92.9% | (88.4‐97.4%) | 2.53 | (1.14‐5.62%) | |
| High‐grade cytology | 40/51 | 78.4% | (67.1‐89.7%) | 19/37 | 51.4% | (35.2‐67.5%) | 69.0% | (57.1‐80.9%) | 63.3% | (46.1‐80.6%) | 1.88 | (1.14‐3.10%) | |
| CIN2+ | NILM | 10/23 | 43.5% | (23.2‐63.7%) | 236/341 | 69.2% | (64.3‐74.1%) | 8.7% | (3.5‐13.8%) | 94.8% | (92.0‐97.5%) | 1.67 | (0.75‐3.68%) |
| Low‐grade cytology | 26/52 | 50.0% | (36.4‐63.6%) | 100/146 | 68.5% | (61.0‐76.0%) | 36.1% | (25.0‐47.2%) | 79.4% | (72.3‐86.4%) | 1.75 | (1.10‐2.77%) | |
| High‐grade cytology | 51/71 | 71.8% | (61.4‐82.3%) | 10/17 | 58.8% | (35.4‐82.2%) | 87.9% | (79.5‐96.3%) | 33.3% | (16.5‐50.2%) | 1.32 | (1.01‐1.73%) | |
| (C) ASCL1/LHX8 methylation a + HPV16/18 genotyping | |||||||||||||
| CIN3+ | NILM | 8/10 | 80.0% | (55.2‐104.8%) | 200/354 | 56.5% | (51.3‐61.7%) | 4.9% | (1.6‐8.3%) | 99.0% | (97.6‐100.4%) | 4.42 | (0.95‐20.51%) |
| Low‐grade cytology | 17/22 | 77.3% | (59.8‐94.8%) | 92/176 | 52.3% | (44.9‐59.7%) | 16.8% | (9.5‐24.1%) | 94.8% | (90.4‐99.2%) | 5.61 | (1.71‐18.35%) | |
| High‐grade cytology | 47/51 | 92.2% | (84.8‐99.5%) | 10/37 | 27.0% | (12.7‐41.3%) | 63.5% | (52.5‐74.5%) | 71.4% | (47.8‐95.1%) | 2.22 | (0.95‐5.18%) | |
| CIN2+ | NILM | 13/23 | 56.5% | (36.3‐76.8%) | 192/341 | 56.3% | (51.0‐61.6%) | 8.0% | (3.8‐12.2%) | 95.0% | (92.1‐98.0%) | 1.43 | (0.65‐3.19%) |
| Low‐grade cytology | 36/52 | 69.2% | (56.7‐81.8%) | 81/146 | 55.5% | (47.4‐63.5%) | 35.6% | (26.3‐45.0%) | 83.5% | (76.1‐90.9%) | 2.66 | (1.51‐4.66%) | |
| High‐grade cytology | 63/71 | 88.7% | (81.4‐96.1%) | 6/17 | 35.3% | (12.6‐58.0%) | 85.1% | (77.0‐93.2%) | 42.9% | (16.9‐68.8%) | 1.49 | (0.94‐2.37%) | |
Note: Low‐grade cytology: BMD equalling ASC‐US/ASC‐H/LSIL. High‐grade cytology: >BMD equalling HSIL.
Abbreviations: ASC‐H, atypical squamous cells that cannot exclude high‐grade squamous intraepithelial lesions; ASCUS, atypical squamous cells of undetermined significance; CI, confidence interval; CIN, cervical intraepthelial neoplasia; HPV, human papillomavirus; HSIL, high‐grade squamous intraepithelial lesions; LSIL, low‐grade squamous intraepithelial lesions; N, group size; n, number of; NILM, negative for intraepthelial lesion or malignancy; NPV, negative predicted value; PPV, positive predicted value.
Using a predefined threshold (70% specificity).