Our vision is to have screening covering all cancers, available to everyone, everywhere.
The main screening test for cervical cancer detection is the Papanicolaou (Pap) test/smear. A Pap smear is obtained during a pelvic examination where a plastic spatula or brush is used to collect cells from the cervix. The Pap smear transfers the cells from the collection device to a microscope slide. An improved liquid-based cytology (LBC) technique, approved by the FDA in 1996 as a superior technique[i], includes immersing cells in a solution prior to depositing them onto a concave microscope slide. Following the cell transfer in both methods, the slide is prepared using a fixative, then haematoxylin, orange and polychrome staining, followed by an ethanol wash.[ii] A pathologist will then microscopically examine the histology of the collected cells and make a judgement on the neoplastic nature of the viewed cells.
Since the 1940s, the Pap screen has helped to reduce the occurrence of cervical cancer by around 60%.[iii] However, its shortcomings (sensitivity of 30%-87%[iv], specificity of 67%-86%[v]). While physical examination and visual inspections with acetic acid or Lugol’s Iodine continue to be important in areas of low resource, they remain subjective, and have poor regulation and quality control. LBC was adopted in 1990s in the US and parts of Europe, despite its higher per-test cost than the original Pap test. Automated (e.g. Cytoscreen® and Easy Prep) and manual (SurePath and Thin Prep) preparation kits are used to improve the clarity of the sample. There is also automated screening technology such as AutoPap 300 and PAPNET which rely on neural network technology.
All of the systems involve: capturing sufficient cells from the cervix; transferring an adequate cell sample onto a slide; staining samples correctly; and observing and identifying cancerous and pre-cancerous cells by trained technicians and pathologists. Other cancer screening also relies on the preparation of stained cell samples for examination under the microscope.
As an alternative to microscopic examination at the cellular level, there are also research spectroscopy and photonic techniques that have shown the ability to detect cancer at molecular levels. For example, Fourier Transform Infrared[vi] and Raman Spectroscopy[vii] are optical techniques which can differentiate cervical cancer tissue from healthy tissue. Photonic-crystal biosensors can also be used to detect cancers.[viii] However, algorithms in these techniques lack automated classification and ability to feedback to improve accuracy.[ix] Additionally, unlike OMIS these techniques are hampered by artefacts, penetration issues or drift anomalies and are only able to sense a single type of cancer.
There are alternative methods to reduce the incidence of, and mortality from, cervical cancer such as screening for Human papillomavirus (HPV; which can cause cervical cancer) and vaccinating against HPV.[x] HPV screening methods have higher sensitivity detecting 23% more early stage cancers than cytology methods.[xi] However, this is contentious as the nature of the virus is transient and may not be present in a screening session.[xii] In conjunction with cytology smears, the HPV screen could be used to triage women at higher risk, although this adds cost and complexity to the screening programme.
Tumour Trace’s OMIS Cancer Screening Technology
With our technology; Opto-magnetic Imaging Spectroscopy (OMIS) – of which several research studies have now validated and proved the concept (please see Case Studies for results) – it is now possible to conduct non-invasive tests with a sensitivity of 95.00%, and a specificity 94.44%, whilst delivering results in a much shorter time frame; 10 minutes instead of 7 days.
This presents a very promising opportunity indeed for the future of early cancer detection and prognosis for patients. With guidance from the National Institute for Health Research (NIHR), Tumour Trace has now agreed protocols to begin the process of conducting extensive peer approved clinical trials to further validate our science and the efficacy of our cancer screening system.
[ii] Denny, L. (2012). Cytological screening for cervical cancer prevention. Best Practice & Research Clinical Obstetrics & Gynaecology, 26(2), 189-196.
[iii] US Department of Health & Human Services. National Institutes of Health. http://report.nih.gov/nihfactsheets/viewfactsheet.aspx?csid=76
[iv] National Institutes of Health
[v] Gibb R and Martens M. (2011). The Impact of Liquid-based Cytology in Decreasing the Incidence of Cervical Cancer. Reviews in obstetrics and gynecology, 4(Suppl 1), S2.
[vi] Krishna et al. (2006) “Raman spectroscopy studies for diagnosis of cancers in human uterine cervix.” Vibrational Spectroscopy 41: 136-141.
[vii] Ali S et al. (2013) “A comparison of Raman, FTIR and ATR-FTIR micro spectroscopy for imaging human skin tissue sections.” Analytical Methods 5.9: 2281-2291.
[viii] Chan L, Gosangari S, Watkin K and Cunningham B (2008) “Label-free imaging of cancer cells using photonic crystal biosensors and application to cytotoxicity screening of a natural compound library” Sensors and Actuators B, Vol. 132, p. 418-425.
[ix] Baker M et al. (2014) “Using Fourier transform IR spectroscopy to analyze biological materials.” Nature protocols 9.8: 1771-1791.
[x]A Strategy for Cancer
[xi]Arbyn M et al. (2006)
[xii]Arbyn M, Sasieni P, Meijer C, Clavel, C, Koliopoulos G and Dillner J. (2006). Clinical applications of HPV testing: a summary of meta-analyses. Vaccine, 24, S78-S89.
The Opto-Magnetic Imaging spectroscopy (OMIS) method for detecting cancer cells has the same initial steps as current Pap and LBC methods; however, the subsequent preparation and interpretation of cell traits is where the OMIS method and device present a technological breakthrough.
OMIS is used to resolve differences in the paramagnetic and diamagnetic properties of tissues based on unpaired and paired electrons and hydrogen bonds. Cancerous cells have more free water molecules than normal cells, and malignancy increases with the degree of cell hydration.[i] There are complex water cluster dynamics in cells which can be investigated using optical reflectance microscopy and Brewster angle microscopy which OMIS brings together.
The process involves shining white light on the sample, which interacts with the valence electrons to produce a measure of the molecules’ electrical and magnetic forces. Analyses of resulting images allows OMIS to detect changes in the paramagnetic and diamagnetic states of tissue hydration. The data output can be read as a spectral signature and used to detect cancerous cells. In malignant spectra, there are lower peak intensities and a noticeable shift in peak positions when compared with normal cells’ spectra. Multiple spectra are processed by a statistical learning algorithm (SLA) to build a frequency intensity matrix which is strengthened with every reading. Therefore, it is in this objective diagnosis that OMIS presents a significant innovation enabling the benefits highlighted below:
- Reduces the time taken for the patient to receive the result from a sample (c.5 minutes compared to average 2 weeks)
- Removes the subjective interpretation of even the most highly-trained technician and improves accuracy (90% specificity and 95% sensitivity)
- It is significantly cheaper than the state of the art technologies which all require a skilled technician (60%-75% reduction in laboratory costs)
- Increases the certainty and belief in the result for the screening provider and the patient
- The hardware is a simple camera and light emission source omitting the need for complex optics and lasers
- The hardware is portable and needs minimal maintenance
- Imaging by visible light is non-invasive and avoids damage to the sample material
- Samples can be read with or without stain
- Since energy of valence electrons and photons of visible light has the same value imaging by visible light and is non-invasive, it provides an examination process that can be repeatedly conducted without presenting any risks to the patient or sample material damage.