TABLE 3.
Level of evidence for the association of risk factors for cervical cancer (Liaoning, China. 2021).
| Risk factor | Features used for classification of level of evidence | Evidence class e | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Significance threshold reached a | I2 (95% CI) | 95% prediction interval | Egge’s p value | Excess significance b | Largest study significant | Small-study effect/excess significant bias | |||
| O/E c | p value d | ||||||||
| Life style | |||||||||
| Past smokers | >0.05 | 0 (0–90) | (0.10–7.68) | 0.733 | 0/0.3406 | 0.5354 | No | No/No | NS |
| Current smokers | >0.05 | 37 (0–80) | (0.01–68.02) | 0.657 | 0/0.5316 | 0.4215 | No | No/No | NS |
| Past smokers | >0.05 | 68.4 (0–91) | (0.00–615.58) | 0.251 | 0/1.1615 | 0.1686 | No | No/No | NS |
| Current smokers | <0.05 but >0.001 | 42.7 (0–83) | (0.05–53.22) | 0.343 | 1/0.7286 | 0.7148 | No | No/No | Ⅳ |
| Past smokers | >0.05 | 0 (0–62) | (0.72–1.18) | 0.479 | 0/1.8199 | 0.1358 | No | No/No | NS |
| Current smokers | >0.05 | 20 (0–61) | (0.58–1.39) | 0.599 | 0/1.9952 | 0.1144 | No | No/No | NS |
| Overweight | >0.05 | 19.9 (0–61) | (0.85–1.42) | 0.939 | 2/1.6457 | 0.7600 | Yes | No/No | NS |
| Obesity | <0.05 but >0.001 | 57.2 (10–80) | (0.78–2.72) | 0.170 | 3/2.2797 | 0.5809 | Yes | No/No | Ⅳ |
| Smoking | <10−6 | 64 (5–86) | (0.89–4.96) | 0.434 | 4/2.1087 | 0.0868 | Yes | No/Yes | Ⅱ |
| Virus, microorganism, and parasite | |||||||||
| HPV and HPV16 | <10−6 | 0 (0–90) | (0.18–1547.16) | 0.121 | 3/0.1514 | 0.0000 | Yes | No/Yes | Ⅳ |
| <0.001 but >10−6 | 43.8 (0–81) | (0.42–32.51) | 0.088 | 4/0.8277 | 0.0001 | Yes | Yes/Yes | Ⅳ | |
| Herpes simplex type 2 | <0.05 but >0.001 | 0 (0–48) | (1.03–1.43) | 0.428 | 1/2.9113 | 0.2155 | No | No/No | Ⅳ |
| HPV16 A4/Asian variants | <0.05 but >0.001 | 62.1 (18–32) | (0.42–18.99) | 0.896 | 3/2.2465 | 0.5418 | Yes | No/No | Ⅳ |
| Chlamydia trachomatis infection | <10−6 | 45.6 (0–84) | (0.09–53.34) | 0.960 | 2/0.5946 | 0.0418 | Yes | No/Yes | Ⅳ |
| <10−6 | 47.4 (9–70) | (1.18, 4.06) | 0.337 | 9/5.0139 | 0.0317 | Yes | No/Yes | Ⅱ | |
| Coinfection of HPV and Chlamydia trachomatis | <10−6 | 44.0 (0–78) | (1.31–14.66) | 0.352 | 4/1.2393 | 0.0054 | Yes | No/Yes | Ⅱ |
| Chlamydia trachomatis infection | <10−6 | 31.9 (0–67) | (1.48–2.95) | 0.274 | 5/3.0626 | 0.1838 | Yes | No/No | Ⅰ |
| <0.05 but >0.001 | 0 (0–85) | (0.84–3.04) | 0.122 | 2/0.5205 | 0.0279 | No | No/Yes | Ⅳ | |
| Chlamydia trachomatis infection (serum) | <10−6 | 39.6 (0–66) | (1.42–3.26) | 0.481 | 9/4.5148 | 0.0116 | Yes | No/Yes | Ⅱ |
| Epstein-Barr virus | <0.001 but >10−6 | 76.3 (60–86) | (0.25–63.55) | 0.075 | 7/11.9431 | N/A | Yes | Yes/No | Ⅳ |
| Cervicovaginal lactobacilli | <0.05 but >0.001 | 0 (0–90) | (0.00–343.66) | 0.242 | 2/0.2197 | 0.0001 | Yes | No/Yes | Ⅳ |
| Reproductive factors | |||||||||
| In vitro fertilization | >0.05 | 69 (10–89) | (0.03–34.71) | 0.291 | 1/1.1316 | 0.8839 | Yes | No/No | NS |
| Intrauterine device use | <0.001 but >10−6 | 42.5 (0–68) | (0.38–1.07) | 0.029 | 5/4.9806 | 0.9902 | No | Yes/No | Ⅲ |
| Oral contraceptives use | <0.05 but >0.001 | 67.7 (6–89) | (0.38–7.58) | 0.232 | 3/1.1125 | 0.0352 | Yes | No/Yes | Ⅳ |
| <0.001 but >10−6 | 0 (0–85) | (1.06–2.96) | 0.264 | 3/0.491 | 0.0001 | Yes | No/Yes | Ⅳ | |
| <10−6 | 0 (0–79) | (1.12–1.50) | 0.181 | 1/0.434 | 0.3686 | Yes | No/No | Ⅰ | |
| Oral contraceptive >10 years | <0.001 but >10−6 | 0 (0–90) | (0.13–38.57) | 0.832 | 2/0.5229 | 0.0246 | Yes | No/Yes | Ⅲ |
| Diseases | |||||||||
| Endometriosis | <0.001 but >10−6 | 0 (0–90) | (0.16–2.84) | 0.713 | 2/0.2627 | 0.0004 | Yes | No/Yes | Ⅲ |
| Gestational diabetes mellitus | >0.05 | 0 (0–90) | (0.23–4.49) | 0.037 | 0/0.4407 | 0.4723 | No | Yes/No | NS |
| Nutrients and their levels | |||||||||
| Total vitamin A intake | <10−6 | 77.9 (67–85) | (0.25–1.39) | 0.380 | 9/11.0299 | N/A | No | No/No | Ⅲ |
| Blood vitamin A levels (retinol) | >0.05 | 0.0 (0–90) | (0.15–8.93) | 0.901 | 0/0.1579 | 0.6831 | No | No/No | NS |
| Blood vitamin A levels (carotene) | <0.05 but >0.001 | 69.8 (23–88) | (0.10–2.29) | 0.202 | 3/2.0479 | 0.3409 | No | No/No | Ⅳ |
| Retinol intake | <0.05 but >0.001 | 41.3 (0–74) | (0.46–1.39) | 0.054 | 2/1.8919 | 0.9283 | No | Yes/No | Ⅳ |
| Carotene intake | <0.001 but >10−6 | 82.6 (67–91) | (0.15–1.75) | 0.620 | 5/2.9124 | 0.1094 | Yes | No/No | Ⅲ |
| Carotenoid intake | <0.05 but >0.001 | 52.5 (0–86) | (0.02–19.91) | 0.931 | 2/0.6592 | 0.0615 | Yes | No/Yes | Ⅳ |
| Retinol intake | >0.05 | 0 (0–90) | (0.13–5.32) | 0.553 | 0/0.1833 | 0.6586 | No | No/No | NS |
| Carotene intake | <0.05 but >0.001 | 78.8 (32–93) | (0.00–1239.10) | 0.140 | 2/1.5758 | 0.6238 | Yes | No/No | Ⅳ |
| Serum Selenium levels | <0.001 but >10−6 | 0 (0–79) | (0.35–0.86) | 0.211 | 3/0.5576 | 0.0005 | Yes | No/Yes | Ⅳ |
| Vitamin E | <0.001 but >10−6 | 77.6 (58–88) | (0.19–1.50) | 0.767 | 5/3.8431 | 0.4130 | Yes | No/No | Ⅲ |
Abbreviation: CI, confidence interval; HPV, human papillomavirus.
a
p value under the random-effects model.
b
Expected number of statistically significant studies using the point estimate of the largest study (smallest standard error) as the plausible effect size.
c
Observed/Expected number of statistically significant studies.
d
p value of the excess statistical significance test.
e
Criteria for classification of the credibility of the evidence. Ⅰ, Strong; Ⅱ, Highly-suggestive evidence; Ⅲ, Suggestive evidence; Ⅳ, Weak evidence; NS, Non-significant associations.
All statistical tests two sided.