Serum HE4 and diagnosis of ovarian cancer in postmenopausal women with adnexal masses

Research output: Contribution to journalArticle


  • Aleksandra Gentry-Maharaj
  • Matthew Burnell
  • James Dilley
  • Andy Ryan
  • Chloe Karpinsky
  • Richard Gunu
  • Stuart Campbell
  • Ian Jacobs
  • Usha Menon


Transvaginal ultrasound and serum CA125 are routinely used for differential diagnosis of pelvic adnexal mass. Use of Human Epididymis 4 (HE4) was approved in the United States in 2011. However, there is scarcity of studies evaluating the additional value of HE4.

To evaluate the performance characteristics of transvaginal ultrasound, CA125 and HE4 for differential diagnosis of ovarian cancer in postmenopausal women with adnexal masses.

Study design
Cohort study nested within the screen arms of the multicentre randomised controlled trial United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), based in England, Wales and Northern Ireland. In UKCTOCS, 48,230 women randomised to transvaginal ultrasound screening and 50,078 to multimodal screening (serum CA125 interpreted by Risk of Ovarian Cancer Algorithm with second line transvaginal ultrasound) underwent the first (prevalence) screen. Women with adnexal lesions and/or persistently elevated risk were clinically assessed and underwent surgery or follow-up for a median of 10.9 years. Banked samples taken within 6 months of transvaginal ultrasound from all clinically assessed women were assayed for HE4 and CA125. Area under the curve and sensitivity for diagnosing ovarian cancer of multiple penalized logistic regression models incorporating logCA125, logHE4, age and simple ultrasound features of the adnexal mass were compared.

Of 1,590 (158 multimodal, 1432 ultrasound) women with adnexal masses, 78 were diagnosed with ovarian cancer (48 invasive epithelial ovarian - 14 Type I, 34 Type II; 24 borderline epithelial; 6 non-epithelial) within one-year of scan. The area under the curve (0.893 vs 0.896;p=0.453) and sensitivity (74.4%vs75.6%;p=0.564) at fixed specificity of 90% of the model incorporating age, ultrasound and CA125 was similar to that also including HE4. Both models had high sensitivity for invasive epithelial ovarian (89.6%) and Type II (>91%) cancers.

Our population cohort study suggests that HE4 adds little value to concurrent use of CA125 and transvaginal ultrasound in the differential diagnosis of adnexal masses in postmenopausal women.


Original languageEnglish
Pages (from-to)56.e1-56.e17
JournalAmerican journal of obstetrics and gynecology
Issue number1
Publication statusPublished - Jan 2020


  • ovarian cancer, ovarian neoplasm, CA125, HE4, TVS, ultrasound, risk of malignancy, diagnosis, adnexal mass, UKCTOCS, human epididymis 4, United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), transvaginal ultrasound

ASJC Scopus subject areas