Although the prevalence of ovarian cancer is fairly low, it is often asymptomatic until after metastasis, resulting in it being the fourth leading cause of cancer death in females in the USA. The development of biomarker screening tests for ovarian cancer has been challenging and the situation is still not satisfactory. Additionally, the tests that have been developed do not perform equally in all sectors of the population. CLI caught up with Dr Twiggs and Dr Fritsche from Aspira Women’s Health® (formerly known as Vermillion, Inc.) to find out more about the tests available for ovarian cancer and how to improve equity of diagnosis in all sectors of the female population.

What is the incidence and prevalence of ovarian cancer?

A woman’s lifetime risk of developing ovarian cancer has been estimated at 1.2%. Ovarian cancer represented only 1.1% of new cancer diagnoses in 2021. However, it’s lethality is noteworthy as it is the fourth leading cause of cancer death in females in the USA. The 5-year relative survival for ovarian cancer is only 49.1%, as the initial diagnosis is usually made when the disease has metastasized. Only 16.3% of ovarian cancer cases are diagnosed when the cancer is limited to the ovary (early stage). The earlier the cancer is diagnosed, the higher the chance of survival. When ovarian cancer is diagnosed at the localized stage, the 5-year relative survival is 92.6% [1].

Micrograph of a serous papillary carcinoma (adenocarcinoma) of ovary, with intricately branching papillae (Shutterstock.com)

How is ovarian cancer normally diagnosed?

As ovarian cancer is usually diagnosed in late stages, it is not surprising that many patients present with symptoms. These symptoms may be vague and include abdominal bloating, increased girth, fatigue, gastrointestinal disturbances, urinary symptoms, abdominal/pelvic pain and menstrual irregularities [2,3]. The clinical challenge is to identify patients who present with adnexal masses that are malignant. The challenge is formidable, as in the USA approximately 1.2–1.5 million patients present with adnexal masses but only 20 000 patients are diagnosed with ovarian cancer. It has been estimated that from 200 000 to 400 000 surgeries are performed annually for adnexal masses [4–7]. Adnexal masses represent an important opportunity for early ovarian cancer detection. These masses may be discovered incidentally or upon evaluation for patient complaints such as pelvic pain or frequent urination. Identification of a malignant adnexal mass is clinically challenging. Ultrasound imaging of the mass and tumour marker testing are routinely used to identify a mass at high risk for cancer. Referral of a patient who is at high risk for cancer to a gynecologic oncologist for surgery is the recommended medical management. Data have shown that surgery performed by a gynecologic oncologist results in higher rates of complete tumour removal, and better overall survival [2–3].

Unfortunately, there is no screening test for ovarian cancer, as there is for cervical cancer. Efforts to develop a simple screening test have not been successful. Therefore, early detection efforts have led to assessing cancer risk on the basis of family history or genetic alterations. Evaluating patients for the risk of ovarian cancer when the patient has symptoms, family history of cancer or an adnexal mass relies on intense clinical acumen using radiologic and ultrasound imaging combined with serum tumour marker testing.

Ovarian cancer illustration (Shutterstock.com)

Moreover, recent studies have shown that ethnic disparity exists in clinical performance between MIA and ROMA (CA125 and HE4) in detection of ovarian malignancy risk. This is partially due to the fact that certain non-white populations, such as the African American population, are known to have lower circulating levels of CA125 [9]. This, in turn, makes the assessment less effective in this population.

The MIA, Ova1, was shown to be superior to ROMA in the detection of ovarian cancer in African American women [10]. It has been shown that the implementation of MIA in the evaluation of adnexal masses will increase the sensitivity of the detection of malignancy compared with ROMA and CA125 alone, with the most marked results in African American women [10,11]. Likewise, the MIA, Overa® (Aspira Women’s Health), was  shown to outperform CA125 in Filipino women [12].

What future developments do you envisage or would like to see for ovarian cancer diagnosis?

Real success in the field of detection of ovarian cancer will rely on screening tests, coupled with ultrasound and clinical assessment. Those screening tests will help to identify patients with early stage ovarian cancer, when survival outcome is best achieved.

This goal of early detection is limited by the difficulty of defining ovarian cancer in its preclinical phase. There must also be continual efforts made to ensure that innovations in early cancer detection serve all patient populations equitably and effectively. Hope emanates from the development of new serum protein and genetic biomarkers for improved risk assessment and for the application of early detection biomarkers in these high-risk groups. If such markers are identified and become part of the standard of care, diagnostic intervention could initiate early treatment or preventive methods leading to improved survival and cure rate for this lethal disease.

References

1. Cancer stat facts: ovarian cancer. In: Surveillance, Epidemiology, and End Results Program [website]. National Cancer Institute 2023 (https://seer.cancer.gov/statfacts/html/ovary.html).
2. Evaluation and management of adnexal masses. Practice bulletin number 174. American College of Obstetricians and Gynecologists 2016 (https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2016/11/evaluation-and-management-of-adnexal-masses).
3. Multiplex serum testing for women with pelvic mass. Position statements, ovarian cancer. Society of Gynecologic Oncology issued 2011, updated 2013 (https://www.sgo.org/resources/multiplex-serum-testing-for-women-with-pelvic-mass/).
4. Torre LA, Trabert B, DeSantis CE et al. Ovarian cancer statistics, 2018. CA Cancer J Clin 2019;68(4):284–296. doi: 10.3322/caac.21456 (https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21456).
5. Glanc P, Benacerraf B, Bourne T et al. First international consensus report on adnexal masses: management recommendations. J Ultrasound Med 2017;36(5):849–863. doi: 10.1002/jum.14197 (https://onlinelibrary.wiley.com/doi/10.1002/jum.14197).
6. Giede KC, Kieser K, Dodge J, Rosen B. Who should operate on patients with ovarian cancer? An evidence-based review. Gynecol Oncol. 2005;99(2):447–461. doi: 10.1016/j.ygyno.2005.07.008 (https://www.gynecologiconcology-online.net/article/S0090-8258(05)00597-4/fulltext).
7. Mobeen S, Apostol R. Ovarian cyst. StatPearls Publishing 2022 (https://www.ncbi.nlm.nih.gov/books/NBK560541/).
8. Dunton CJ, Hutchcraft ML, Bullock RG et al. Salvaging detection of early-stage ovarian malignancies when ca125 is not informative. Diagnostics 2021;11(8):1440. doi: 10.3390/diagnostics11081440  (https://www.mdpi.com/2075-4418/11/8/1440).
9. Sasamoto N, Vitonis AF, Fichorova RN et al. Racial/ethnic differences in average CA125 and CA15.3 values and its correlates among postmenopausal women in the USA. Cancer Causes Control
2021;32:299–309. doi: 10.1007/s10552-020-01384-z (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887701/).
10. Dunton C, Bullock RG, Fritsche H. Multivariate index assay is superior to CA125 and HE4 testing in detection of ovarian malignancy in African-American women. Biomark Cancer 2019;11:1179299X19853785. doi: 10.1177/1179299X19853785 (https://journals.sagepub.com/doi/10.1177/1179299X19853785).
11. Dunton C, Bullock RG, Fritsche H. Ethnic disparity in clinical performance between multivariate index assay and CA125 in detection of ovarian malignancy. Future Oncol 2019;15(26):3047–3051. doi: 10.2217/fon-2019-0310 (https://www.futuremedicine.com/doi/10.2217/fon-2019-0310).
12. Velayo CL, Reforma KN, Sicam RVG et al. Improving diagnostic strategies for ovarian cancer in Filipino women using ultrasound imaging and a multivariate index assay. Cancer Epidemiol 2022;81:102253. doi: 10.1016/j.canep.2022.102253 (https://www.sciencedirect.com/science/article/pii/S1877782122001588?via%3Dihub).

The interviewees

Dr Leo B. Twiggs MD
Director of Medical Affairs, Aspira Women’s Health, Austin, TX 78738, USA
Professor Emeritus Miller School of Medicine University of Miami,
Miami, FL, USA

Email: ltwiggs@aspirawh.com

Dr Herbert Fritsche PhD
Laboratory Director, Aspira Women’s Health, Austin, TX 78738, USA
Email contact via Victoria Haverbusch: vhaverbusch@aspirawh.com
For further information visit Aspira Women’s Health: https://aspirawh.com/