Ovarian cancer has a 5-year survival rate of only 50.9%. That's a toss of a coin.
One of the most critical factors behind this statistic is the stage at diagnosis. The earlier a person is diagnosed, the higher the 5-year survival rate becomes. Unfortunately, for ovarian cancer, this diagnosis often occurs too late for effective intervention. But could that be about to change?
Recent studies by Salem et al. and Winn-Deen et al. (2024) explore a novel diagnostic approach: using extracellular vesicles (EVs) as ovarian cancer biomarkers.1,2 Could EVs offer a non-invasive, highly sensitive and specific method for detecting ovarian cancer markers – outperforming traditional diagnostics such as CA125?
Ovarian cancer: low incidence, high stakes
Why does early diagnosis matter so much for ovarian cancer? The answer lies in the diagnostic gap between high- and low-incidence cancers.
For all cancers, diagnostic tests must balance specificity and sensitivity. High specificity minimises false positives, reducing unnecessary anxiety and unwarranted treatments, while high sensitivity ensures no cases are overlooked. This balance is especially challenging – and critical – for low-incidence cancers like ovarian cancer, where the rarity of the disease increases the risks of both missed diagnoses and misdiagnoses.
Consider the contrast between breast cancer and ovarian cancer. Breast cancer, a high-incidence cancer, benefits from established routine screening programs. In 2022, 2.3 million women were diagnosed with breast cancer, which has a 5-year survival rate of 90%.3 In contrast, ovarian cancer saw 324,603 new cases, with a significantly lower 5-year survival rate of just 50.9%.4 The key difference? Breast cancer has effective early-detection tools, while ovarian cancer lags behind.
When caught at a localised stage, the 5-year survival rate for ovarian cancer jumps to 91.9%. This makes the potential impact of early diagnosis clear and pressing. Early diagnosis expands treatment options, highlighting the urgent need for improved diagnostic strategies.5 So why aren’t we screening for ovarian cancer the way we are for breast cancer?
The limitations of current ovarian cancer screening methods
Sensitive and specific screening tests are urgently needed to improve outcomes for ovarian cancer patients. Current screening methods, such as transvaginal ultrasound imaging and the CA125 blood test, struggle to meet the necessary sensitivity and specificity thresholds. By the time ovarian cancer is diagnosed using these methods, it is often too advanced to benefit from conventional surgery and chemotherapy.6
To be a successful tumour biomarker, the protein or RNA needs to be detectable at low concentrations and resilient enough to withstand processing without degrading. However, traditional tests like CA125 have limitations. The CA125 blood test, which measures a protein that ovarian cancer cells can produce, can yield false positives in non-cancerous conditions and benign masses, leading to unnecessary surgeries and patient anxiety.
While the CA125 test can be useful in monitoring ovarian cancer, it lacks sensitivity in the early stages, as the protein levels may not be high enough to detect. Additionally, elevated CA125 levels can occur in other conditions, reducing its specificity. Large randomised control trials (RCTs) have explored combining CA125 testing with transvaginal ultrasound, with limited 8 to no 7 success. Even when some improvement in diagnosis was seen, it was not enough to significantly reduce ovarian cancer deaths, with the authors stating that general population screening cannot be recommended with this approach.8 However, hope is not lost. A new EV-based test may be on the horizon.
Extracellular vesicles: towards a novel ovarian cancer test
Two recent studies by Salem et al., 2024, and Winn-Deen et al., 2024, aim to tackle these diagnostic challenges by using EVs as biomarkers. EVs are small particles released by cells that carry proteins and genetic material that are reflective of their cell of origin. Since they are stable and abundant in blood and can carry tumour-specific markers, EVs are a promising tool for early cancer detection.
To pave the way for more accurate, early-stage diagnosis, Salem et al. (2024) developed an EV-based liquid biopsy test targeting three ovarian cancer biomarkers which were identified using a computational biomarker discovery approach. These three winning proteins were BST2, FOLR1, and MUC1. To isolate these biomarkers, the researchers collected EVs from several sources. These were human cancer cell lines, as well as more physiologically relevant plasma samples from healthy donors, women with benign ovarian masses, and patients with early- and late-stage high-grade serous ovarian cancer (HGSOC). EVs were purified from concentrated conditioned media or human plasma using qEVoriginal 70 nm Legacy columns. (FYI, we have a new resin now and it’s even better than its Legacy predecessor).
Once isolated, the EVs were captured using magnetic bead-antibody conjugates targeting the identified surface biomarkers. The clever part is that these antibodies were conjugated to DNA oligos which are complimentary to each other, meaning that presence and colocalisation of these biomarkers can be confirmed using qPCR amplification. For a visualisation of how this technology works, take a look at Figure 2.
This OC test was then verified by Winn-Deen et al. (2024). By analysing these three surface biomarkers, the researchers sought to distinguish between healthy individuals, those with ovarian cancer, and those with confounding conditions such as benign adnexal masses. They also compared these results with the conventional CA125 test.
It should be noted that the verification study used qEV original 70 nm Gen 2 columns (those new and improved ones we mentioned earlier), with Gen 2 columns being found equivalent for diagnostic value.
This verification study found that the correlation between OC test scores and 10-year survival outcomes was also assessed across different ovarian cancer stages and types. Overall, survival was higher for those diagnosed at earlier stages and with lower OC test scores, although the OC test score itself could not predict survival outcomes. A trend toward higher test scores in patients with poorer outcomes suggests that the assay may help gauge cancer severity at diagnosis, which could guide treatment strategies.
In addition to providing important clinical information in ovarian cancer cases, the OC test also reduced the likelihood of false positives seen with conventional tests like CA125.
With the OC test, doctors could, therefore, have a more precise and specific readout of ovarian cancer-associated biomarkers, reducing the likelihood of false positives commonly seen with conventional tests like CA125.
A promising step forward for diagnosing ovarian cancer
These studies present a significant methodological advancement over current ovarian cancer early-screening protocols. By leveraging EVs as biomarkers and the novel biomarker combination design, the test achieves higher specificity and sensitivity than CA125 testing. This is especially hard to do in low-incidence cancers, making this an important development. If implemented in the clinic, the tests improved accuracy should reduce unnecessary procedures for benign conditions and inflammatory diseases, lowering healthcare costs and patient anxiety.
By combining high specificity with minimal invasiveness, this OC test could transform early-stage ovarian cancer detection and potentially reduce mortality by enabling timely intervention. As research advances, this approach may extend to other cancers, offering hope for a more precise and accessible means of early detection.
Are you working on an EV biomarker study? If so, we can help you scale from bench to bedside with qEV PurePath for Diagnostics.
