Ovarian cancer recurrence and early detection: may HE4 play a key role in this open challenge? A systematic review of literature

Despite the improvement in overall survival for ovarian cancer (OC) patients, a fraction of patients with advanced-stage disease fails to respond to primary therapy and relapses in 70% of cases. For this reason, new predictive and monitoring tools are needed to identify OC recurrence and new biomarkers were studied, among which human epididymis 4 (HE4), primarily expressed in the reproductive and respiratory tracts, is one of the most promising, reporting a good sensitivity and specificity in detecting OC, overcoming the traditional role of carbohydrate antigen 125 (CA-125). In this review, we aim to discuss the latest evidence reported in the literature about the use of HE4 to monitor ovarian cancer treatment and to detect OC recurrence. We searched MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, IBECS, BIOSIS, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) from January 1952 to June 2017. The search identified seven papers in line with eligibility criteria for this systematic review; all of them demonstrated a good performance of HE4 in OC recurrence. The challenge to anticipate the diagnosis of OC recurrence and to translate this early diagnosis of relapse in a survival and quality of life improvement is still open, and as reported in this review, HE4 may play a key role in this scenario. More studies are needed to validate and reinforce the role of HE4 in ovarian cancer recurrence and in its early detection.