The continuous variables ROMA and CPH-I in this study have several nonstandard distributions. Therefore, the statistics of ROMA and CPH-I will be presented as median values (Q25% – Q75%).
The median values of CPH-I and ROMA in the OC group, as shown in Table 3, were higher than those of the benign tumor group and borderline tumor group. Specifically, for the study population (n = 475), the median value of CPH-I in the malignant group was 24.81% (3.49 – 81.21%), whereas in the benign tumor group, it was 0.42% (0.29 – 24.39%), and those in the borderline tumor group were 0.42% (0.29 – 24.39%). The median values of ROMA in the cancer group, borderline group, and benign group were 49.93% (12.78 – 81.22%), 5.48% (3.28 – 16.38%), and 5.03% (3.46 – 8.71%), respectively (p < 0.05). Compared to previous studies, the median values of CPH-I and ROMA from our research are lower than those of some other studies in the world. According to Adriana Yoshida (2016), the median values of CPH-I for benign tumors and ovarian carcinomas were 1.4% and 83.4%, respectively (12). Meanwhile, in Lubos Minar’s study, the median values of CPH-I in the benign and malignant groups were 2.2% and 75.4%, respectively (14) (Table 5). More detailed analysis in the premenopausal and postmenopausal groups, which examined the differences between CPH-I and ROMA, showed that the median values of CPH-I and ROMA were higher in the postmenopausal group than in the premenopausal group (Table 3). The median values of CPH-I and ROMA in the postmenopausal group were higher than those in the premenopausal group. The sensitivity/specificity (Se/Sp) of CPH-I in the absence of marginal ovarian tumors, nonepithelial OC, and OC metastasis was 89.7%/85.3%, but if the above objects were included, the corresponding Se/Sp became lower at 73.1%/84.4% (12).
The Se/Sp of ROMA and CPH-I in the diagnosis of OC were 76.1%/87.0% and 83.6%/78.7%, respectively. The optimal cut-off point of the CPH-I was 1.89%, and the AUCs of ROMA and CPH-I were 0.860 (95% CI: 0.825 – 0.890) and 0.868 (95% CI: 0.833 – 0.896), respectively. Research by T. Nikola (2017) differential diagnosis between ovarian endometriosis and ovarian carcinoma showed that the accuracy of the Copenhagen Index was higher than that of ROMA, 93.75% and 85.42%, respectively (15).
Zhiheng Wang et al. (2019) argued that the HE4 level and ROMA and CPH-I values of epithelial ovarian cancer (EOC) stages I and II (I + II) were all higher than those of borderline ovarian tumor (BOT) stages I + II and benign groups in all premenopausal and postmenopausal groups (p < 0.01). When distinguishing BOT I+II from EOC I+II, the AUC-ROCs of CPH-I and HE4 were larger than that of CA-125 (p < 0.001). CPH-I is more valuable than CA-125 when distinguishing marginal ovarian tumors from stage I – II ovarian carcinoma, while HE4 may be better than CA-125 in the postmenopausal group; HE4 and CPH-I have been more advantageous than CA-125 when differentiating a borderline ovarian tumor from an early-stage ovarian carcinoma (I + II) in the absence of histology or type of serum fluid. The AUCs of CPH-I and ROMA in the premenopausal group were 0.779 and 0.760, respectively, and those in the postmenopausal group were 0.802 and 0.774, respectively. In the premenopausal group, the Se/Sp of ROMA and CPH-I were 78.69%/64.75% and 70.49%/78.69%, respectively. In the postmenopausal group, the Se/Sp of ROMA and CPH–I were 82.98%/68.18% and 85.11%/68.18%, respectively (16).
According to Estrid Høgdall, ROMA and CPH–I can be used for the differential diagnosis between benign and malignant ovarian tumors [13]. Since family doctors might be unable to perform an ultrasound test, both ROMA and CPH-I could provide the initial reliable information, which helps the patient obtain early diagnosis and proper treatment from specialized centers. In general, CPH-I and ROMA have similar sensitivity and accuracy. CPH-I is not identical to ROMA and RMI because it is not independent of ultrasound test and menopausal status. Menopausal status can be determined based on age, hormone concentration or amenorrhea per year, so the diagnosis of menopausal status has not been standardized. Therefore, CHP-I could be a simpler method to optimize management when assessing women with suspected OC, including age instead of menopausal status (11,17).
The Copenhagen Index is a new indicator that has been introduced in several studies around the world. The ROMA algorithm is an index that the US Food and Drug Administration has introduced in clinical practice to distinguish benign and malignant ovarian tumors based on three variables: CA-125, serum HE4, and menopausal status (19). These two indexes have quite similar values since both are partially based on CA-125 and HE4. Since serum CA-125 and HE4 concentrations are affected by many factors, including age, smoking, uterine fibroids, pregnancy, endometriosis, pelvic inflammatory disease, and gallbladder stones, this will affect the values of the Copenhagen index and ROMA (20,21). In the future, more research on these two indicators on different target groups will be conducted to clarify these differences, aiming to overcome the limitations of these indicators and improve clinical practice.
To the best of our knowledge, this is the first cohort study from Vietnam with a large number of ovarian tumor subjects included, examining the validity of CPH-I and comparing it with those from ROMA in risk stratification for ovarian tumor malignancy. Although rigorously designed and implemented, the OC cases were still limited, and the laboratory equipment was different at the two facilities where the work was done, which could partially affect the homogeneity of the data analysis.