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Raman spectroscopy for early diagnosis of oral pre-cancer and cancer using minimally invasive samples

Periodic Reporting for period 1 - RAMAN-Dx (Raman spectroscopy for early diagnosis of oral pre-cancer and cancer using minimally invasive samples)

Reporting period: 2018-08-01 to 2020-07-31

In 2018, there were an estimated 354,864 cases of lip, oral cavity and pharyngeal cancers and the incidence and a mortality of 177,384. The 5 year survival rate for oral cancer for Europe is only 50% and patients often present with advanced disease. Multiple primary tumours and field cancerization are common and there is a high risk of developing secondary tumours. Therefore, it is of paramount importance to diagnose the disease early. Diagnosis of oral pre-cancer and cancer starts with conventional oral examination by the clinician followed by biopsy and histopathology. This is regarded as the gold standard but is subjective and depends upon visual examination so sensitivity and specificity can be poor at the early stages of the disease. Hence, there is a significant need for new diagnostic techniques to detect pre-malignant lesions.
The overall objective of this project was to develop new methods based on Raman spectroscopy for probing biochemical changes associated with oral pre-cancer and its progression. During the project, a comprehensive time-gated Raman spectral library containing high-quality Raman spectra measured from oral samples from patients and normal subjects was established. Furthermore, a SERS spectral library of salivary samples was developed. In addition to training through research, the MSCA fellow was trained in transferable skills such as project management, communication skills, networking, ethics, gender equality and IPR management.
During the project, time-gated Raman spectra were collected from each sample in the biobank and a comprehensive Raman spectral database of negative cytology and low grade and high grade oral cytology samples was developed. It was established that it was possible to detect pre-cancer related changes in the oral cavity by analysing the exfoliated cell samples using time-gated Raman spectroscopy and that excellent sensitivity and specificity could be achieved for identifying the high grade dysplasia cases from low grade dysplasia cases and normal cases based on the spectral dataset obtained from the exfoliated cells.
Histology results were obtained from the Dublin Dental University Hospital. A chemometric model was developed which showed that negative, low grade and high grade dysplasia could be discriminated very well by both time-gated Raman spectroscopy of exfoliated cells and by SERS of saliva.
The results were presented at several conferences and two papers are in preparation.
Training-through-research was provided by the host laboratory and training in transferable skills was provided throughout the MSCA fellowship. The MSCA fellow transferred knowledge in software development and multivariate analysis to the host laboratory members and also to the host’s wider research network.
Intersectoral transfer of knowledge was provided through a secondment at VTT Technical Research Centre, Finland. This allowed the researcher to experience working in a non-academic environment which has been very beneficial for her career development. She was also given training in time-gated Raman spectroscopy. At the end of the secondment, the researcher was offered a permanent Senior Application Specialist position at Timegate Instruments Oy, which is a spin-off of VTT.
The results obtained during this MSCA fellowship have shown that the cellular biochemical fingerprint obtained using Raman spectroscopy can pave the way for future screening and surveillance of suspicious oral lesions. This new method based on time-gated Raman spectroscopy is a novel, cost-effective solution to distinguish between dysplasia and normal samples. This would aid in early diagnosis of oral cancer leading to better prognosis for the patient.
Currently there is no clinically practised method to diagnose precancer non-invasively. This research has addressed an unmet clinical need to develop new methods to objectively identify patients with dysplasia with minimally invasive sampling by employing exfoliated cells and even non-invasive sampling using saliva.
In addition to research training, and transferable skills training, the MSCA fellow also benefited from intersectoral training in the non-academic sector for her secondment. This resulted in a permanent Senior Application Specialist position for the MSCA fellow.