Real-time Molecular Diagnosis of Oral Precancer

Oral cancers are severe life-limiting diseases, particularly when diagnosed in late stages. Earliest possible detection in precancer (dysplasia) or early cancer stages is the single most important measure for reducing oral cancer patients' morbidity and mortality rates. Conventional diagnosis relies on visual inspection guiding the biopsy of suspicious oral lesions, which has resulted in 5-year survivals of up to 90% for early tumors or dysplasia. This survival rate however declines to at best 50% for advanced cancers, highlighting the necessity of early diagnosis as a primary factor in determining patient outcomes. Visually guided tissue sampling suffers from inter-observer dependence, sampling errors and difficulty in identifying and targeting flat dysplastic lesions in particular. The differentiation between inflamed/scarred tissue and dysplasia, establishing cancer depth, local/distant spread assessment (staging) and grading (aggression), and margin assessment of malignant lesions, all represent monumental clinical challenges. Further, biopsy also remains a significant deterrent to patient attendance. There is a significant unmet clinical need for a rapid, non-invasive, outpatient-deployable diagnostic method to improve surveillance, early diagnosis, and follow up / management of oral cancer patients.

Optical imaging and spectroscopy have recently offered great promise to address unmet clinical needs since they are non-invasive and can capture molecular/structural information without prior tissue preparation. These technologies offer new, clinically relevant biomarkers such that essential point-of-care decisions can be made with the use of safe (non-ionizing) levels of optical radiation at a much lower cost than with MRI, CT and PET. Raman spectroscopy is a label-free, rapid and minimally invasive optical technique using laser light that provides a point-wise optical fingerprint of the myriad of inter- and intra-cellular building blocks of tissue (i.e., proteins, lipids and DNA) at the biomolecular level. Raman spectroscopy offers label-free diagnosis of cancers in vivo. In the last two decades, there has been accumulating evidence on the accurate diagnostic capability of Raman spectroscopy through comprehensive in vitro, ex vivo and in vivo studies.

The research team have developed a 2nd generation polarized Raman platform that provides polarized Raman signals and is compatible with the oral cavity. It can provide a point-wise vibrational molecular fingerprint "optical biopsy" of both tissue structure/molecular symmetries and composition. The key advantage of polarized Raman spectroscopy compared to conventional Raman spectroscopy is that it offers additional specific information about tissue structure and organization. The developed prototype is fully functional and will allow us to take the first step towards translation of the developed clinical platform technology.

In this study, patients with suspected pre-cancer or being seen by a clinician for early oral cancer will be recruited. The participants will be scanned with the LIP device and will have a biopsy if this was planned as part of their routine care. Health volunteers will be recruited to increase the number scans of healthy tissue and to help validate the device. The primary aim of this study is to collect the output of the scans and train the device to discriminate premalignant/malignant conditions from benign oral tissue. No clinical output will be provided at this stage, thus diagnosis of suspicious lesions will be confirmed through a biopsy according to standard NHS procedures. Secondary aims include collecting pilot safety data, and feedback from users of the device and study participants.

Inclusion criteria

for patients

• Adult aged 18 and older
• One of the following criteria must be met:

• Has a medical condition for which biopsy of oral tissue has been indicated.
• Is undergoing inspection for early oral cancer
• Willing and able to comply with all study procedures.

Exclusion criteria

for patients

• Has a bleeding disorder, such as haemophilia, or has contraindication for having a biopsy.
• Severe co-morbid illness, such as end-stage renal failure (ESRF), congestive cardiac failure (CCF), severe osteoarthritis (OA) and rheumatoid arthritis (RA) requiring long term non-steroidal anti-inflammatory drug (NSAID) therapy and any other immunosuppression / immuno-modulation therapy.
• Has other severe acute or chronic medical or psychiatric condition where use of the device may cause unnecessary stress
• Any condition that under judgment of the investigator would make the subject unsuitable as it may interfere with interpretation of study results
• Currently using any compound recognised as acting as a light sensitizer / has a recognised condition associated with light sensitisation / tissue sensitivity to light such as photodynamic therapy or lupus.
• Is pregnant or breastfeeding
• Has a laboratory abnormality in medical record that may interfere with the interpretation of study results

Inclusion criteria

for healthy volunteers

• Adult aged 18 and older.
• Willing and able to comply with all study procedures.

Exclusion criteria

for healthy volunteers

• Has a medical condition for which biopsy has been indicated or is undergoing inspection for early cancer.
• Severe co-morbid illness, such as end-stage renal failure (ESRF), congestive cardiac failure (CCF), severe osteoarthritis (OA) and rheumatoid arthritis (RA) requiring long term non-steroidal anti-inflammatory drug (NSAID) therapy and any other immunosuppression / immuno-modulation therapy.
• Has other severe acute or chronic medical or psychiatric condition where use of the device may cause unnecessary stress
• Any condition that under judgment of the investigator would make the subject unsuitable as it may interfere with interpretation of study results
• Currently using any compound recognised as acting as a light sensitizer / has a recognised condition associated with light sensitisation / tissue sensitivity to light such as photodynamic therapy or lupus.
• Is pregnant or breastfeeding