Abstract

Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.

Highlights

  • Head and neck cancer (HNC), primarily comprising squamous cell carcinomas of the oral cavity, oropharynx, and larynx, represents the 6th most common cancer worldwide.[1]

  • Change in light intensity versus frequency plots were constructed for each sample tested successfully using DEP. Upon examination of these DEP spectra, it became evident that differences between oropharyngeal carcinoma (OOPC) and healthy control oral brush biopsies (OBBs) spectra occurred at the low frequency area of the plots, i.e. at frequencies ≤1 MHz.[29]

  • This indicated that differences between OOPC and healthy OBB samples were found at frequencies which cannot penetrate the cells’ plasma membranes, the movement of cells suspended in the DEP Well was indicative of the electrophysiological characteristics of the cells’ plasma membranes

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Summary

Introduction

Head and neck cancer (HNC), primarily comprising squamous cell carcinomas of the oral cavity, oropharynx, and larynx, represents the 6th most common cancer worldwide.[1] The incidence of HNC is rising, mainly due to the increasing incidence of human papilloma virus (HPV)-related oropharyngeal carcinomas.[2] Mortality rates remain high, with current data indicating that more than half of individuals with HNC die of their disease within five years of diagnosis.[3] Most oral and oropharyngeal carcinomas (OOPCs) are preceded by longstanding clinical changes of the oral mucosa, mainly white (leukoplakia) and red (erythroplakia) patches.[4] Prompt identification and histological examination of these mucosal abnormalities can translate into diagnosis of early-phase OOPC, i.e. at a stage of disease associated with favorable prognosis.[4] early superficial OOPC is often difficult to clinically discern from common benign oral disease, and incisional biopsy is always warranted to confirm the potentially malignant nature of oral lesions.[5] Referral to secondary care for diagnostic incisional biopsy and subsequent histopathology is often delayed until the disease progresses to a more advanced, easier to detect but less curable stage, partially accounting for the high mortality of OOPCs.[4,5,6,7]

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