Quantifiable Changes in Nuclear Chromatin Structure of Oral Epithelium Based on Smoking Pack-Years in the Progression of Oral Squamous Cell Carcinoma (OSCC)

Abstract

The process of oncogenesis in the oral mucosa to oral squamous cell carcinoma (OSCC) initiation by tobacco smoke has been studied extensively worldwide. However, many questions remain. Across many fields, clinical and epidemiological data has shown that there is an association between tobacco and the development of OSCC and its oncogenic pathways1. Different studies have shown that tobacco can cause abnormal expression of key regulatory proteins, such as p53, MGMT, P13K, GLUT-1, p16, DAPK, along with other regulatory genes in the oral epithelium associated with the incidence of OSCC2. Despite the advancements in preventive and therapeutic treatment methods, there still remains a delay in OSCC diagnosis that contributes to predominantly elevated morbidity and mortality2,3. The majority of OSCC cases are identified in advanced clinical stages, such as stage III or IV. After primary treatment, recurrences of OSCC are found in more than half of patients, with 80% of cases found within the first 2 years following primary treatment3. Additionally, the 5-year survival rate is still lower than 50%, despite preventative and therapeutic strategies3. These factors indicate a serious public health issue. Currently, histological investigation is considered the “gold standard” of OSCC diagnosis. However, recent studies are now looking at the potential of using saliva, or a “liquid biopsy”, to detect biomarkers in the bodily fluids of OSCC patients. While promising, it is important to point out that these techniques are still dependent on the collection of saliva and our ability to detect cytokines, DNA molecules, RNA molecules, and circulating biomarkers. There is another promising method to detect biomarkers in the early diagnosis of OSCC patients: karyometry. Karyometry provides a process to identify a quantifiable integrating biomarker by looking at small nuclear changes that cannot be detected by the trained eye. A karyometric analysis may give us useful information regarding the early diagnosis of OSCC and disease progression. Our primary objective is to access the functionality of karyometric analysis in identifying and integrating biomarkers on the progression of OSCC. We will be running karyometric analysis on the oral epithelium to see the impact of smoking tobacco on the development of carcinogenesis to OSCC. It is our intent to show the several promising clinical uses karyometry and how it can be used in the detection and management of OSCC. Karyometry is painless, accessible, and low-cost source of helpful data for diagnostic and prognostic biomarker detection. It is worth exploring the potential benefits karyometry may have in cancer prevention.