Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature
Abstract
:1. Introduction
2. Methodology
3. Results
3.1. Tumour Marker CA125
3.2. Tumour Marker HE4
3.3. HE4 + CA125 Association
3.4. Multimodality Screening
3.5. Trial Description
3.6. Early Detection in the High-Risk Population
3.7. Tests Based on Prognostic and Predictive Biomarkers in Patients with Symptoms
3.8. New Screening Tools
3.9. Risk of Malignancy Index (RMI)
3.10. ROMA Algorithm
3.11. OVA 1 Test
3.12. Improving the Performance of Additional Biomarkers
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Reference. Author and Year | The Systemic Revision or Metanalysis | CA125 | HE4 | CA125 + HE4 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Se (%) (95% IC) | Sp (%) (95% IC) | PPV (%) | NPV (%) | AUC (95% IC) | Se (%) (95% IC) | Sp (%) (95% IC) | PPV (%) | NPV (%) | AUC (95% IC) | Se (%) (95% IC) | Sp (%) (95% IC) | PPV (%) | NPV (%) | AUC (95% IC) | ||
[19] Ferraro S. et al., 2013 | X | 79 (77–82) | 78 (76–80) | 79 (76–81) | 93 (92–94) | 82 (78–86) | 76 (72–80) | |||||||||
[20] Wang J et al. 2014 | X | 79 (74–84) | 82 (77–87) | 0.87 (0.84–0.90) | 76 (72–80) | 94 (90–96) | 0.89 (0.86–0.92) | |||||||||
[21] Zhen et al. 2014 | X | 74 (72–76) | 83 (81–84) | 0.85 | 74 (72–76) | 90 (89–91) | 0.89 | |||||||||
[27] Meys et al. 2016 | X | |||||||||||||||
[28] Li et al. 2012 | X | 77 (58–89) | 84 (76–90) | 0.88 (0.85–0.91) | 79 (74–84) | 93 (87–96) | 0.82 (0.78–0.85) | |||||||||
RMI | ROMA | |||||||||||||||
[20] Wang J et al. 2014 | X | 85 (81–89) | 82 (77–87) | 0.91 (0.88–0.93) | ||||||||||||
[27] Meys et al. 2016 | X | 75 (72–79) | 92 (88–94) | |||||||||||||
Al Musalhi et al. [29] 2016 | X | 77 | 82 | 56 | 93 | 0.85 | 75 | 88 | 65 | 92 | 0.84 | |||||
[28] Li et al. 2012 | X | 89 (84–93) | 83 (77–88) | 0.93 (0.90–0.95) |
Name of the Study | Study Design | Screening Cohort Size | Screening Strategy | Interpretation CA125 | Sensitivity (%) | Mortality/Subrogated Results | Author, Year. (Reference) |
---|---|---|---|---|---|---|---|
PLCO | RCT, on general population | 30,630 | CA125 + TVU | Fixed cut, 35 U/mL | IOC/FT: 69.5 IOC/FT: 68.2 | No mortality benefit | Buys et al. 2011 [31] |
UKCTO | RCT, on | 101,247 | 1. | ROCA | OC/FT: | Relative | Jacobs |
CS | general population, | CA125 following | longitudinal sampling | MMS (89.4)/ | mortality reduction of | et al. 2015 [32] | |
two arms | for MMS | TVU (84.9) | MMS (14%) | ||||
IOC/FT: | and groups of | ||||||
MMS | USS (11%) | ||||||
2. Only | (84.9)/ | about no | |||||
TVU | TVU (75.0) | action, but | |||||
IOC/FT: | the reductions | ||||||
MMS | were not | ||||||
(88.6)/ | significant in | ||||||
TVU (65.8) | the primary | ||||||
analysis | |||||||
Japanes e cohort Shizuoka | RCT, low risk post-menop ausal | 41,688 | Physical examinat ion, CA125 and TVU | Fixed cut, 35 U/mL | OC/FT: 77.1 | Change of stage; Stage I OC in screening (63%) versus | Kobayashi et al. 2008 [35] |
Control (38%) |
Evaluated Marker or Combination of Markers | ROC-AUC (95% CI) | p Value vs. ROMA |
---|---|---|
CA125 | 86.6% (80.6–92.6%) | 0.039 |
HE4 | 90.8% (85.7–95.8%) | 0.671 |
ROMA (CA-125 + HE4 + menopausal) | 91.2% (86.0–96.4%) | ––– |
CA125 + Transthyretin + ApoA1 + Beta2 Microglobulin + Transferrin + menopausal | 89.7% (84.4–95.0%) | 0.502 |
CA125 + HE4 + ApoA1 + Transferrin + menopausal | 93.2% (88.7–97.6%) | 0.153 |
CA125 + HE4 + YKL-40 + Transthyretin + ApoA1 + Beta2 Microglobulin + Transferrin + LPA + menopausal | 94.6% (90.1–99.2%) | 0.078 |
Analysed Value | ROMA (95% CI) | 8 Markers Trial (95% CI) |
---|---|---|
Sensitivity | 90.0% (79.5–96.2%) | 94.0% (83.5–98.7%) |
Specificity | 76.7% (67.3–84.5%) | 76.3% (66.4–84.5%) |
PPV | 69.2% (57.8–79.2%) | 68.1% (55.8–78.8%) |
NPV | 92.9% (85.3–97.4%) | 95.9% (88.6–99.2%) |
Accuracy | 81.6% (74.8–87.2%) | 82.5% (75.3–88.4%) |
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Elorriaga, M.Á.; Neyro, J.L.; Mieza, J.; Cristóbal, I.; Llueca, A. Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature. J. Pers. Med. 2021, 11, 1115. https://doi.org/10.3390/jpm11111115
Elorriaga MÁ, Neyro JL, Mieza J, Cristóbal I, Llueca A. Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature. Journal of Personalized Medicine. 2021; 11(11):1115. https://doi.org/10.3390/jpm11111115
Chicago/Turabian StyleElorriaga, Miguel Ángel, José Luis Neyro, Jon Mieza, Ignacio Cristóbal, and Antoni Llueca. 2021. "Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature" Journal of Personalized Medicine 11, no. 11: 1115. https://doi.org/10.3390/jpm11111115
APA StyleElorriaga, M. Á., Neyro, J. L., Mieza, J., Cristóbal, I., & Llueca, A. (2021). Biomarkers in Ovarian Pathology: From Screening to Diagnosis. Review of the Literature. Journal of Personalized Medicine, 11(11), 1115. https://doi.org/10.3390/jpm11111115