Conquering the Challenges of Colposcopy
A device that uses electrical impedance spectra to characterize abnormal cervical tissue may improve on the subjective nature of colposcopy and reduce the rate of cervical biopsy
Ursula Winters |
One in every 135 women will be diagnosed with cervical cancer during her lifetime – and in recent years, incidence of the disease has increased in younger women (1). Early diagnosis is key, with 96 percent of patients diagnosed at Stage I surviving beyond five years, compared with only 5 percent of those diagnosed at Stage IV (2). This striking difference in survival rates makes it clear that early, accurate diagnosis and long-term survival are two sides of the same coin – and yet our testing methods are flawed, subject to false positives, false negatives, and differences of opinion between differently trained practitioners. But when discussing cervical smear tests and colposcopy, we frequently encounter two arguments: that they save lives, which is certainly true, and that we have no better way of screening. It’s that second argument that my colleagues and I decided to address with a new device that uses electrical impedance to detect and measure cervical tissue changes in women presenting with abnormal smears.
At a Glance
- Both cervical smears and colposcopy are subject to interpretation – and confirmation of abnormality often means one or more cervical biopsies
- The ZedScan device uses electrical impedance spectroscopy (resistance to flow of alternating current) to examine irregularities in cervical cell and tissue structure
- The more abnormal the tissue, the more its structure breaks down and therefore the less resistance it offers to the flow of an electrical current
- The device can also pinpoint the location of abnormal tissue, leading to more accurate sampling with fewer overall biopsies required
Colposcopy – the traditional next step after an abnormal smear test – relies on the presence of visible indicators to detect atypical cells on the cervix. Unfortunately, these indicators are not specific to cervical intra-epithelial neoplasia (CIN), especially low-grade CIN, which means that interpretation is subjective. That’s why we take biopsies to confirm the presence of disease before offering treatment. But biopsies are invasive – and as it can be difficult to judge the best location, we sometimes need to take more than one tissue sample, which can add to patient discomfort. Even after the biopsy is complete, it can take up to two weeks to receive the histology results, making waiting patients understandably anxious. In the majority of cases, the abnormal tissue will regress naturally, so to avoid unnecessary and potentially harmful treatment, we tend to recall these patients for repeat colposcopy at six- to 12-month intervals – only increasing the time and effort, in addition to uncertainty for the patient.
An alternative solution
It’s for these reasons that I am particularly interested in exploring alternative diagnostic methods – and we may have found something that can help… ZedScan allows us to assess the structure of the cervical epithelium based on its electrical impedance spectrum. Normal epithelial tissue has a very regular and structured architecture with tightly packed cells, so it exhibits a high impedance (resistance) to the flow of an electric current. The more abnormal the tissue becomes, the more this architecture starts to break down. That makes it easier for an electric current to pass through the tissue, so the impedance drops. The ZedScan device applies a small current across the cervix and measures the impedance at 14 different frequencies to generate a spectrum.
During a colposcopy procedure, we take 10–12 readings from around the transformation zone, which takes about three minutes in total. Each measurement is compared to a standard, allowing the device to characterize the tissue and identify areas of high-grade dysplasia. Once the examination is complete, results are immediately displayed on the handset. Areas of high-grade disease appear as a red or amber dot on the screen, indicating where the measurement was taken so that we know straight away whether to offer treatment, take a biopsy or discharge the patient.
Electrical impedance spectra improve our team’s ability to identify and treat women with high-grade precancerous CIN – important because the risk of development into cancer is significantly higher than with low-grade dysplasia. ZedScan also yields an objective, reliable and reproducible result – and because we get it in real-time, we have greater ability to employ the “see and treat” method, where women with severe abnormalities can be treated immediately without requiring biopsy. That also eliminates the need to bring patients back at a later date for treatment, minimizing the cost to them in terms of time, effort and anxiety. And negative results are just as useful; we spend a large proportion of clinic time on follow-up appointments to monitor women with low-grade abnormalities. A negative ZedScan result reassures us that no severe abnormalities are present, letting us safely discharge those women to routine screening and free up appointments for new patients.
We’re just starting to adopt ZedScan into routine use at our clinic, but based on feedback from other centers, we anticipate our service will become more efficient, and consequently, more cost-effective. There were some initial concerns that the examination would add to the appointment time for each patient – and when we first began using the new device, it did take a little longer. But with every patient, we became quicker.
In my opinion, the biggest impact on pathology will be a change in the type and number of biopsy samples generated. As we become increasingly confident in offering “see and treat,” the proportion of tissue excisions is likely to increase. I don’t see this increasing the overall pathology workload, though, because it will be offset by a decrease in diagnostic biopsies. Neither women who are both ZedScan and colposcopy negative, nor those undergoing “see and treat” will require biopsy. Even in cases where biopsy is indicated, the new device will help to pinpoint the best site, so that clinicians can take fewer biopsies and – as indicated by clinical studies, feedback from other centers and a health economics study – reduce the burden on histology by as much as 60 percent.
Addressing unmet needs
In my opinion, ZedScan addresses the current unmet needs in colposcopy by providing a more objective and reliable diagnosis and helping to identify the optimum site for biopsy.
The technology also supports detection of high-grade cervical intraepithelial neoplasia which may be less obvious on colposcopic examination, so is effective in patients with non-HPV16 disease which may be associated with less aceto-white change. This is increasingly important as HPV 16/18 vaccination will change the epidemiology of disease.
The detection of glandular disease in colposcopy continues to be challenging, as there are no specific colposcopic features on which to base a diagnosis. Anecdotal evidence from other centers suggests that the device can detect glandular disease even without co-presenting squamous disease – and if further studies bear that out, it would be a real bonus for colposcopists.
Women with a type 3 cervix (one where the transformation zone has an endocervical component) also present a challenge. The squamocolumnar junction, where disease tends to develop first, is located within the endocervical canal and is therefore not visible under colposcopic examination. To accurately detect and diagnose disease in this type of cervix, we would need to be able to take measurements from within the endocervical canal. At the moment, the ZedScan device can identify ectocervical lesions that extend into the endocervical canal, but isn’t able to examine lesions without an ectocervical component.
The introduction of electrical impedance spectra will allow us to assess women presenting with abnormal cervical smears more quickly and accurately. That means we can offer our patients rapid access to appropriate treatments when they need them, reassure those with no evidence of disease, and reduce the overall number of biopsies needed.
Zilico, the Manchester company behind ZedScan, was founded in 2006 after a successful collaboration between the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust to develop a more accurate means of diagnosing cervical intraepithelial neoplasia (CIN). Brian Brown of the University of Sheffield and John Tidy of Sheffield Teaching Hospitals developed Zilico’s patented electrical impedance spectroscopy (EIS) into a platform technology for cervical cancer diagnosis, and the company is now expanding its product development into other clinical areas. We interviewed Sameer Kothari, Chief Executive Officer at Zilico to find out more…
What are the current unmet needs incervical diagnostics?
The first stage of screening has improved significantly in recent years, but it remains a subjective test. Cytopathologists and their colleagues assess the cells present in a cervical smear for the presence of changes suggestive of dysplasia. Despite improvements in education, training and the organization of screening programs, all cervical screening programs based on cytology are subject to both false positives and – more worryingly – false negatives. The next stage of testing is colposcopy – and here too, results depend on what an individual colposcopist judges to be normal or abnormal. A colposcopic diagnosis of abnormality is subjective, and can sometimes result in differences of opinion. In addition, it’s very difficult to get representative images or video that can allow the diagnosis to be “quality-assured” by colleagues. The final stage is biopsy and, as in screening, results are interpreted in the laboratory. There is room for error in each of these stages, and the entire process can take a long time when patients have to wait for the results of each test.
What are the next steps for the development of this technology?
ZedScan’s sister product, currently under development, is positioned within the cervical screening pathway. It will provide a real-time diagnosis at the point-of-care, thus reducing traffic between primary care, cytology laboratories and colposcopy clinics – and resulting in a more effective application of limited healthcare resources. Using the same EIS technology as ZedScan, this product discriminates underlying tissue in the same way and will be subjected to a screening trial, which will determine whether it will be used as a triage system or as a co-test with either cytology or human papillomavirus (HPV) molecular tests. In countries where the testing infrastructure – cytology laboratories, sample logistics, and administrative support – is lacking, women have very restricted access to cervical cancer screening. Our EIS products will provide an opportunity to screen and manage patients at the point of care, instead of transporting them to urban centers for tests that can take several days. The technology is applicable to a wide range of cancer types with significant changes to the cells and target tissue structure. In collaboration with the University of Sheffield’s School of Clinical Dentistry, we’ve completed a proof-of-concept clinical study using EIS to discriminate between oral tissues, including neoplasia – and we have further studies planned in the areas of anal, esophageal, thyroid and bowel cancer.