Real-time tracking of hypoxia glycolysis in conization samples for cervical intraepithelial neoplasia detection

Although cervical cancer in adult women with early diagnostic tests has better treatment ability and disease management, precise and fast diagnosis of any signs of cervical intraepithelial neoplasia (CIN) I-III and high-risk dysplasia is vital. If any precancerous/abnormal suspicious cells are not detected in the routine diagnostic process (pathology), they cannot be treated before the lesion turns into cervical cancer, consequently help increasing the patient’s survival rate.

In this clinical study, the efficiency and diagnostic accuracy of the electrochemical measuring device of glycolysis metabolism in cancer cells (HEA: Hypoxia electrochemical assay) on in-vitro human fresh cervical samples were studied. The samples were prepared from 40 candidates of conization through a history of abnormal cell presentation in their pap smear results. The study was conducted at the Gynecology Department, Yas Hospital, Tehran University of Medical Sciences, and assistant hospitals from August 2018 to June 2021. Patients provided consent according to an ethically approved protocol. A CIN-based scoring of HEA responses was proposed by considering the pathology reports of HEA-tested regions.

The diagnostic calibration of the sensor was achieved by comparing the ROS/H2O2 electrochemical current related to cell glycolysis with the presence of cancer cells in the samples' histology. The current diagnostic threshold obtained by the sensor to differentiate cancerous areas from others showed an accuracy of 95% (P<0.0001). The accuracy and sensitivity of the sensor were 95% and 100%, respectively. Therefore, a matched clinical diagnostic classification between the pathological results of tested tissues and the sensor's electrochemical ROS/H2O2 response was proposed based on CIN categorization.

Further pathological evaluation of the tested samples showed that electrochemical detection of glycolysis metabolism in cervical conization specimens could detect 10% of CIN lesions missed by conventional pathology of assayed patients, which was confirmed in the pathology re-examination. Therefore, as a complementary method, it can help better diagnose CIN lesions in the conization.