Diagnostic Accuracy Of Urine HE4 In Patients With Ovarian Cancer: A Meta-analysis

Objective: Ovarian cancer,the most lethal tumor type among gynecologic cancers,is the fifth most common cause of cancer death in women.Each year,220 000 women develop epithelial ovarian cancer worldwide.Since its lethality may be due to the lack of specific symptoms,effective screening strategies and early diagnostic methods,over 75% of the patients are diagnosed at an advanced stage(stage III or IV),and the 5 year survival rate is only 20%~25%.Nevertheless,the 5-year survival rate for stage I ovarian cancer is up to 83.4%~89.6%.Therefore,the early diagnosis of malignant ovarian tumors is a key factor for improving the survival rate of patients.Urine HE4 has been reported as the potential novel diagnostic biomarker for ovarian cancer in several studies,but their results were inconsistent.Therefore,we conducted a systematic analysis to evaluate the diagnostic value of urine HE4 in detecting ovarian cancer.Methods: A search of diagnostic test studies was performed in 4 English databases(PubMed,Cochrane Library,Web of Science,and Embase)and 3 Chinese databases [China National Knowledge Infrastructure(CNKI),WANFANG and CBM]from their inception dates to May 2016.Two investigators independently conducted the literature search,study selection,data extraction,and quality evaluation.The quality of the studies included in the systematic review was assessed using the Quality Assessment of Diagnostic Accuracy Studies(QUADAS-2)tool.The first to test for heterogeneity,if no statistical heterogeneity between studies,using fixed effect model of Meta-analysis;if the study was statistically significant among the heterogeneity,with the exclusion of obvious clinical heterogeneity,the random effects model analysis and Meta-analysis.Sources of heterogeneity were analysed using subgroup analysis and sensitivity analysis.All analyses were conducted using STATA 12.0 and MetaDisc 1.4 software.Results: A total of seven publications were included in this study,and these studies included 413 ovarian cancer patients and 573 controls.The summary estimates were: sensitivity 0.76(95% confidence interval [CI]: 0.72 ~ 0.80),specificity 0.92(95% CI: 0.89~0.94),positive likelihood ratio 8.39(95%CI: 4.81~14.63),negative likelihood ratio 0.23(95% CI: 0.13 ~ 0.39),diagnostic odds ratio 37.90(95% CI:18.69~76.83),and area under the curve 0.93.Conclusions: The current evidence suggests that urine HE4 can be used for screening and diagnosis of ovarian cancer,and diagnosis using this non-invasive method could be highly efficient.However,due to the quality of the included studies and the fact that patients suspected of having ovarian cancer were not included,and included in the report is a single center study,a limited number of samples,further research studies with more well-designed and large sample sizes are needed in the future.