Non-invasive diagnostic tools in early detection of oral epithelial dysplasia

Oral health promotion and examinations have contributed to the early detection of oral cancer and oral potentially malignant disorders, leading to the adaptation of minimally invasive therapies and subsequent improvements in the prognosis/maintenance of the quality of life after treatments. However, the accurate detection of early-stage oral cancer and oral epithelial dysplasia is particularly difficult for conventional oral examinations because these lesions sometimes resemble benign lesions or healthy oral mucosa tissues. Although oral biopsy has been considered the gold standard for accurate diagnosis, it is deemed invasive for patients. For this reason, most clinicians are looking forward to the development of non-invasive diagnostic technologies to detect and distinguish between cancerous and benign lesions. To date, several non-invasive adjunctive fluorescence-based detection systems have improved the accuracy of the detection and diagnosis of oral mucosal lesions. Autofluorescence-based systems can detect lesions as a loss of autofluorescence through irradiation with blue-violet lights. Photodynamic diagnosis using 5-aminolevulinic acid (ALA-PDD) shows the presence of very early oral cancers and oral epithelial dysplasia as a red fluorescent area. In this article, currently used fluorescence-based diagnostic methods are introduced and discussed from a clinical point of view.

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SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia—a phase II randomised control trial study protocol

Trials ◽

10.1186/s13063-021-05373-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Caroline McCarthy ◽

Joseph Sacco ◽

Stefano Fedele ◽

Michael Ho ◽

Stephen Porter ◽

...

Keyword(s):

High Risk ◽

Sodium Valproate ◽

Study Protocol ◽

Epigenetic Reprogramming ◽

Epithelial Dysplasia ◽

Phase Iii ◽

Cancer Development ◽

Randomised Control Trial ◽

Oral Epithelial Dysplasia ◽

Oral Epithelial

Abstract Background Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study. Methods One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial. Discussion The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial. Trial registration The trial is registered with the European Clinical Trials Database (Eudra-CT 2018-000197-30). (http://www.isrctn.com/ISRCTN12448611). The trial was prospectively registered on 24/04/2018.

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