In an effort to increase the accuracy of cervical cancer diagnoses, a team of researchers is developing a urine test that looks for methylation (a mechanism used by cells to control gene expression) in four genes and, at this early stage, shows evidence of both dramatically improving detection of cancer and enhancing physicians’ ability to determine that a woman does not have cancer. Their work was recently published in the Cancer Prevention Research journal. This news release on the test is something of an explanatory tour de force that explores the path taken to develop the test, but it may require a great deal of effort to follow that path. The release doesn’t give enough attention to the potential downside of the test — a real risk of under-diagnosis — and fails to clearly signal that this diagnostic effort is still at an early stage, making the validity and eventual availability of the test uncertain.
Most cases of cervical cancer occur in developing countries, where Pap tests may be less available for cultural or cost reasons. A urine test that costs less than current diagnostic procedures and that provides increased diagnostic accuracy would offer significant public health advantages in these countries.
This study seeks to address whether a simpler tests could be used to screen initially positive Pap/HPV results in a way that eliminates the falsely positive ones while keeping all of the ones that really need definitive treatment. The investigators used several DNA tests that show promise, but still aren’t perfect. Here the key parameter of interest is sensitivity. You want this to be as close to 100% as possible. Every miss could mean serious consequences for the affected woman. Specificity is less important — it means that the test wasn’t any better than the initial Pap/HPV, and a woman (living in the developed world) might be referred on to a colposcopy test. Whether further studies will show the advantage of this new test or a similar one remains to be seen. But what is really needed is a simple urine screening test that could replace the internal exam that is needed for the current Pap/HPV. Such a test would be useful in both the developed and developing world. That would be a game-changer.
The release suggests that a urine test would be less costly than a Pap test, but it makes no effort to indicate what the cost is of either the proposed test or a Pap test.
We rate this a borderline satisfactory. On the one hand, the release offers numerical summaries of the test’s abilities to both correctly detect cancer (sensitivity) and correctly identify someone who does not have the disease (specificity). But the text does a relatively dense job of explaining how the investigators reached the urine-test stage, creating a narrative that will require a determined reader and could thwart someone giving the text a more cursory view.
The release does make it clear that this small urine test study correctly identified those without cancer 83% of the time, a considerable improvement over the false positive rate of the more traditional Pap test.
But the real risk of this new test is that it may indicate a false negative — suggesting all is well — when it isn’t. Under the best of scenarios, the new test gets it wrong 10 in 100 times. When applied to a more usual practice setting, it gets it wrong 15 to 25 in 100 times. Here getting it wrong may mean missing an advanced pre-cancerous lesion or even a cancerous one. One can argue that even 1 in a 100 times is too much, but in developing countries this may be better than current practice. However, we don’t believe the risk of false negatives has been clearly or addressed.
The release offers a good bit of detail about the researchers’ path to the urine test, a process that involved isolating relevant genes and testing blood samples before turning to urine sample tests. This description gets specific about the size of the various samples used and, if read carefully, yields a reasonable understanding of the studies conducted. Left unsaid is that a “proof-of-concept” study is an early stage in the process of developing a diagnostic test.
Disease-mongering is not a feature of this release. The focus of the release is on a new, presumably cheaper test for cervical cancer, a major killer in less developed countries. The release also puts the problem of cervical cancer screening in global context.
Although the release offers no information about possible conflicts of interest (the article on which the release was based indicates the absence of such conflicts), it does provide information about funding. And it does disclose the start of a collaboration between the team and a company that intends to design and market a urine test product.
The text does a good job of comparing this potential urine test to the traditional Pap smear and to two relatively new commercial tests based on a search for methylation in DNA.
From the data provided, this new test offers no advantages in developed countries where Pap/HPV rates are high and follow-up with colposcopy is available. The issues in developing countries are two-fold. One is whether a urine test could be used as an alternative to the Pap smear/HPV test as the first screen. A urine test would be a much easier screening test. But what they’re examining is when the Pap/HPV is abnormal, can you can eliminate the need for some colposcopies.
All depends on a reader’s understanding of the nature of a proof-of-concept study. This urine test is not yet available, but that will be murky to non-specialists unless the term is defined. Reading between the lines it is evident that further testing is needed before it can be used as part of routine care.
The writer does a good job of making the case for novelty here.
The text is explanatory and not dominated by florid language or predictions. However, if the trial’s results came from better tissue samples than would routinely be available (sophisticated lab sampling versus testing performed in a clinic) the release may paint a rosier picture of the test than is warranted.
Systematic, Criteria-Driven
The @nytimeswell effort is shown to be unwell once again.
There's pervasive media bias toward hyping treatment benefits while neglecting negative results & harms.
Big part of this is reliance on experts with financial &/or intellectual conflicts of interest.
Att'n journalists: Use this list 100 independent experts to correct imbalance https://t.co/Twzc1Sp8Vw
Comments
Please note, comments are no longer published through this website. All previously made comments are still archived and available for viewing through select posts.
Our Comments Policy
But before leaving a comment, please review these notes about our policy.
You are responsible for any comments you leave on this site.
This site is primarily a forum for discussion about the quality (or lack thereof) in journalism or other media messages (advertising, marketing, public relations, medical journals, etc.) It is not intended to be a forum for definitive discussions about medicine or science.
We will delete comments that include personal attacks, unfounded allegations, unverified claims, product pitches, profanity or any from anyone who does not list a full name and a functioning email address. We will also end any thread of repetitive comments. We don”t give medical advice so we won”t respond to questions asking for it.
We don”t have sufficient staffing to contact each commenter who left such a message. If you have a question about why your comment was edited or removed, you can email us at feedback@healthnewsreview.org.
There has been a recent burst of attention to troubles with many comments left on science and science news/communication websites. Read “Online science comments: trolls, trash and treasure.”
The authors of the Retraction Watch comments policy urge commenters:
We”re also concerned about anonymous comments. We ask that all commenters leave their full name and provide an actual email address in case we feel we need to contact them. We may delete any comment left by someone who does not leave their name and a legitimate email address.
And, as noted, product pitches of any sort – pushing treatments, tests, products, procedures, physicians, medical centers, books, websites – are likely to be deleted. We don”t accept advertising on this site and are not going to give it away free.
The ability to leave comments expires after a certain period of time. So you may find that you’re unable to leave a comment on an article that is more than a few months old.
You might also like