Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: Oral squamous cell carcinoma (OSCC) is a prevalent cancer affecting an estimated 377,713 people worldwide, with 58,450 new cases projected in the US for 20241. Most OSCC cases are detected at late stages, where the 5-year survival rate decreases to 40%, compared to 86% for early-stage diagnoses, resulting in considerable morbidity and reduced quality of life2. OSCC diagnosis relies on biopsies, which are costly, time-consuming, anxiety-inducing, and often inaccessible in under-resourced areas. Electrical impedance spectroscopy (EIS) measures electrical properties of tissues, which vary by composition and morphology, enabling noninvasive, low-cost, radiation-free differentiation of tissue types3. EIS effectively distinguishes benign from malignant tissue in the cervix and prostate3,4. This study aimed to demonstrate significant differences in electrical impedance between healthy, dysplastic, and malignant oral tissues.
Methods: Seventy-one patients undergoing OSCC resection at a tertiary care center were enrolled under an IRB-approved protocol. Electrical impedance was measured using a custom-designed 11mm diameter electrode array with a 3D-printed probe, capturing data from in vivo lesions and healthy tissue. Sample resistance, reactance, phase and impedance magnitude were recorded at 31 logarithmically-spaced frequencies between 0.1-100kHz and analyzed using MATLAB. Unpaired t-tests compared impedance parameters across tissue groups (healthy vs malignant, healthy vs dysplastic, and dysplastic vs malignant), with results validated against pathologic assessments at each probe site.
Results: Reactance is significantly lower in malignant compared to healthy tissue (p<0.001) for frequencies <80kHz. Resistance is significantly lower (p<0.05) at all frequencies except 20-32kHz. Malignant tissue impedance magnitude is significantly lower than healthy tissue p<0.01 up to 50kHz and p<0.05 to 65kHz. AUC analysis demonstrates impedance magnitude 0.873 at 400Hz, resistance 0.872 at 315 Hz and reactance 0.873 at 4kHz.
Dysplastic tissue impedance magnitude is significantly lower (p<0.05) compared to healthy tissue from 50-100kHz. Resistance (p<0.05) and reactance (p<0.05) are significantly lower in dysplastic tissue compared to healthy tissue between 12.5-50kHz and 50-100kHz, respectively.
Malignant tissue impedance magnitude is significantly lower than dysplastic tissue (p<0.05) from 100Hz-20kHz. Resistance is significantly lower (p<0.05) in malignant vs dysplastic tissue for all frequencies except 8-20kHz. Reactance is significantly lower (p<0.05) in malignant vs dysplastic tissue up to 50kHz.
Conclusions: We demonstrate that EIS is a safe and effective way to distinguish oral cavity healthy from cancerous and dysplastic tissue based on its electrical characteristics. In vivo measurements of oral cancer and dysplastic tissues have significantly lower impedance parameters compared to healthy oral tissue. Resistance and reactance measurements lend themselves well to distinguishing between malignant and healthy tissue given AUC>0.85.
References:
1. Tan, Y., et al. (2023). Oral squamous cell carcinomas: State of the field and emerging directions. International Journal of Oral Science, 15(1).
2. Siegel, L., et al. (2020). Cancer statistics. CA: a cancer journal for clinicians, 70(1), 7-30.
3. Abdul, S., et al. (2006). The use of electrical impedance spectroscopy in the detection of cervical intraepithelial neoplasia. Int J Gynecol Cancer, 16:1823-1832.
4. Halter RJ, et al. (2009). Electrical properties of prostatic tissues: II. spectral admittivity properties. J Urol, 182:1608.