CPH-I and HE4 Are More Favorable Than CA125 in Differentiating Borderline Ovarian Tumors from Epithelial Ovarian Cancer at Early Stages

AIM: To evaluate the diagnosis value of serum human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the Risk of Ovarian Malignancy Algorithm (ROMA), and Copenhagen Index (CPH-I) at early stages for differentiating borderline ovarian tumors from epithelial ovarian cancer. METHODS: We recruited 144 borderline ovarian tumors in FIGO stages I and II (BOT I+II), 108 epithelial ovarian cancers in FIGO stages I and II (EOC I+II), and 238 benign ovarian tumor patients with surgical treatment in the retrospective study. The concentration of HE4 and CA125 and the values of CPH-I and ROMA were assessed separately. RESULTS: The HE4 level and ROMA and CPH-I values of EOC I+II were all higher than that of BOT I+II and benign groups whether in all, pre-, or postmenopausal groups (P < 0.01). When distinguishing BOT I+II from EOC I+II, the AUC-ROC of CPH-I and HE4 were bigger than CA125 (P < 0.001), while the CPH-I has the highest sensitivities in all and postmenopausal groups (78.7%, 85.1%), and HE4 has the highest specificity and PPV (90.91%, 88.64%) in postmenopausal groups. Under pathological stratification, HE4, ROMA, and CPH-I of the serous EOC I+II were higher than that of BOT I+II (P < 0.001) and the AUC of the three indices were significantly bigger than CA125 (P < 0.001). However, the concentration of HE4 and CA125 and the values of CPH-I and ROMA have no significant difference between the two endometrioid subgroups. The index with the highest sensitivity and NPV among the four indices of different pathological subtype groups was CPH-I, and the index with the highest specificities and PPV was HE4. CONCLUSION: CPH-I was more valuable than CA125 for differentiating BOT I+II from EOC I+II regardless of menopausal status, while HE4 might be better than CA125 for postmenopausal subgroups. HE4 and CPH-I were more favorable than CA125 for differentiating BOT I+II from EOC I+II in the case of unknown pathology or in serous type.