# Comparative Analysis of COL9A1 Genotyping in Oral Squamous Cell Carcinoma Diagnosis: A Pilot Study
## 1 Introduction  
Oral cancer has become an aggressive malignancy with an important impact on the global healthcare system [11]. Out of all oral malignancies, oral squamous cell carcinoma (OSCC) has been reported in more than 90% of cases [12]. The current problem related to this disease, besides late diagnosis, is the fact that it has developed a certain resistance to the therapeutic treatment, a fact that influences further prognosis. This tumour, as a matter of fact, has a high mortality rate, and relapses after surgery and other therapies, such as chemotherapy and radiation therapy, are frequent [11]. An explanation for the unappropriated response of the malignancy to treatment could be the complex and yet not completely known interaction between the environmental variables and the developed genetic variations. Although recent progress has been made concerning diagnosis and treatment options, the survival rate of these patients is still limited, representing ~50% [13]. ]. In order to improve the prognosis of this type of malignancy, a complete diagnosis needs to also include the concept of existing epigenetic mechanisms that can be negatively influenced by environmental factors. Existing studies suggest that the associated oncogenic factors, such as alcohol, human papillomavirus (HPV), tobacco, exogenous carcinogens and lifestyle habits, can determine the epigenetic alterations that are involved in tumour progression and metastasis incidence [10]. Approximately 20% of the oral dysplasia cases progress into malignant lesions [11]. One concern during histopathological examination is the presence or absence of histologically safe margins. Studies reveal that in the case of positive histological margins, the recurrence of OSCC is 70-80%, while in the case of negative margins, recurrence is 30-40% [10]. In their study, [PERSON] et al. [10] discussed the fact that local recurrence or the incidence of a second primary tumour can be linked to existent molecular changes in the entire oral mucosa. An increased understanding of the major role that epigenetic alterations play in the initiation, progression and survival rate of oral cancer patients can aid in developing new approaches in the prevention and early diagnosis field as well as in the management of the at-risk population group. Oral tissue is directly influenced by the presence of various environmental factors that can induce abnormal changes. The disturbance of epigenetic enzymes and signalling pathways promote the growth of malignant cells and facilitates metastasis [10]. Although the published results of several studies focus on various genes as potential biomarkers for OSCC, these findings have not yet been applied in the diagnostic field. An explanation for this could be that the selection of a biomarker is, in many cases, difficult due the fact that it is linked to a large set of data [10]. There are multiple studies that have focused on potential oral cancer biomarkers and their involvement in the early diagnosis, progression and aggressiveness of tumours [10]. An important aspect that needs to be taken into consideration is the determination of the individual risk of developing oral cancer through the quantification of personal genetic mutations and associated environmental risk factors. Molecular characteristics and alterations encountered in oral squamous cell carcinoma reveal the high heterogeneity of the disease, outlining the occurrence in complex anatomical areas with a high number of molecular changes. The Cancer Genome Atlas (TCGA) published a large database concerning genomic data alterations associated with OSCC, outlining the existence of a high number of cancer driver genes that display specific mutational profiles [10]. Until now, multiple genetic mutations have been associated with the incidence of OSCC, but the persisting problem is the diversity among different populations and the presence or absence of a certain gene [11].