One of the main priorities in endo research is the development of new diagnostic tests. Despite improved awareness over the last few years there still remains an unacceptable delay between the onset of symptoms and actually being diagnosed. One of the factors that contributes to this delay is the fact that, currently, endometriosis can only be diagnosed with invasive surgery, which carries the inherent delays and risks associated with such procedures. A non-invasive diagnostic test wouldn’t necessarily replace surgical diagnosis, but it would at least identify women who are more likely to have endo and enable them to be fast tracked to surgery without the needless trial and error of alternative diagnoses.
Therefore it was interesting to see that there’s been a bit of buzz in the media and online recently about a potential new non-invasive diagnostic test for endo (an example of which you can read here). The news makes some interesting claims, for example “The test will be available to buy within nine to 10 months and will cost an estimated £250”. Bold claims indeed, but is any of it true? Lets go through the original research this story is based on and find out.
The research paper (which you can find here) was published in January of this year, and you may think that the news picked up on it because research into new diagnostic methods for endo doesn’t come around very often, but that’s not the case. In fact, searching a science literature database for the terms ‘endometriosis’ and ‘biomarker’ returns nearly 2000 results (a biomarker is any biological factor that when altered in some way by disease can be used as an identifier for that disease) – the latest one just three weeks ago from me writing this. The diagram below summarises most of the research into non-invasive diagnostics and endo as it stands currently.
There’s a more detailed diagram of urine and blood markers that can be found via this link.
So the questions we need to ask is – what makes the paper from January different and, if there is so much research going on, why don’t we have a non-invasive test for endo yet?
The answer to the first question is that this new research looks at something that hasn’t been investigated before. If you look at my diagram above you’ll see there’s a lot of attention paid to proteins and genetic markers in biological fluids and tissues. This new research is still classified as looking at genetic markers (that is, alterations in your DNA), but it is looking at mitochondrial DNA.
Mitochondria are, as the numerous memes insist, the powerhouse of the cell. Mitochondria are tiny structures within your cells that carry out reactions to generate chemical energy to keep your cells alive and doing what they need to do. The vast majority of a cell’s DNA is kept inside another structure, the nucleus, where it is used like a huge instruction manual to produce all the things a cell needs to function.
Mitochondria though, have their own DNA, and this can be useful for a number of reasons; firstly there’s a lot of mitochondrial DNA in each of your cells because there are a lot of mitochondria, so there’s a lot of material to work with, secondly, unlike the DNA in the nucleus, mitochondrial DNA isn’t very good at repairing itself if it gets damaged or mutated – this isn’t a good thing for their function, but it means that any mutations are likely to be retained and could be used as markers for disease (indeed, this has been the case for several types of cancer).
In the case of this new research the authors were looking at a type of mutation that involved the certain small pieces of the mitochondrial DNA being removed (they call them ‘deletions’) and checking to see if any of those deletions were associated with endo. They used blood samples from three groups of women: those with no symptoms and no endo (13 women), those with symptoms but no endo (19 women), and those with symptoms and endo (150 women). It was then a case of using blood samples from these patients to analyse their mitochondrial DNA to see which alterations were most common in women with endo and whether those alterations are good enough to use as a diagnostic test.
The researchers identified two mitochondrial DNA deletions, called ‘1.2kb’ and ‘3.7kb’ that may be useful (the names just refer to how big the deletions were), but in order to talk about how good these would be at identifying women with endo, we need to discuss two terms, sensitivity and specificity.
Sensitivity is how good something is at correctly identifying people with the disease (for example if the sensitivity was 90%, it would mean it could correctly identify 9 out of 10 people who did have the disease, but 1 out of 10 would be shown to not have the disease when they actually did).
Specificity is how good something is at correctly identifying people without the disease (for example if the specificity was 50%, it would mean it could correctly say 5 out of 10 people did not have the disease, but the other 5 would be told they did have the disease when they actually did not).
Let’s take a look at some of the results of the research on the 1.2kb and 3.7kb markers in terms of their sensitivity and specificity when comparing women with symptoms but no endo, to women with symptoms and endo (for the exact details check Table 2 in the research article).
We can see that the tests works well in terms of identifying women with endo (the sensitivity) even for all endo types. However, the specificity is quite low for all disease and deep endo. If we used the 3.7kb marker alone for deep endo it would mean nearly half of the women would test positive for endo, when they did not actually have it. However, the researchers did state that combining the results from 1.2kb and 3.7kb did greatly increase the accuracy of the test.
So the results are very encouraging, does this mean we can use this to diagnose women with endo? The news article I linked to at the beginning stated “The test will be available to buy within nine to 10 [sic] months and will cost and estimated £250”. This sounds promising, but is it true? No.
I’ve no idea where they pulled those timescales and costs from – they certainly aren’t in the original research paper - but there is no way a diagnostic test could be brought to clinical use in that timescale from the current research. Although it’s really good to see such research being done and it definitely paves the way toward new diagnostics in the future, we must be cautious when we hear about it. Why? Well, do you remember I said that there are hundreds and hundreds of research articles already published on non-invasive diagnostics for endo, but no actual diagnostic test yet, there are several reasons for that.
Often a test will work well when undergoing its initial development, but fail later on. There are several reasons for this too. One of the major stumbling blocks is not enough patients were included in the initial research. For example, this new research only had samples from 32 women without endo; do you think this number is high enough to represent the majority of women without endo? Definitely not. This is why these tests have to be repeated with much larger numbers of patients involved, so we can know whether the test works in the general population and not just a select group/s of people.
Other reasons include unexpected factors that may influence the accuracy of the test when it is used in a larger population, like: age, BMI, smoking, diet, ethnicity, other medical conditions, medications, stage of menstrual cycle, stage of endometriosis, and so on. We must give fair credit to the authors of this new research though as they did take into account a lot of these factors when analysing their results, which makes them more reliable.
Nevertheless, we are most likely not ten months away from an accurate, non-invasive test for endometriosis. The fact that so much research is being done is a very positive sign though and with further work hopefully future generations of girls and women will never have to spend years languishing in uncertainty, waiting for a diagnosis.