## 4 Discussion  
Despite the use of concomitant therapies to eradicate OSCC, treatment outcomes have not improved. Factors such as TNM stage, tumour dimension, grading, perineural or vascular invasion, positive lymph nodes, extracapsular extension, nodal location, and size have prognostic significance for local-regional relapse, disease-free survival, and overall survival. To improve the treatment of OSCC, molecular markers were investigated to predict their prognostic values for the selection of the most appropriate treatment modality for better outcomes and survival (23; 25). Most head and neck squamous cell carcinomas (HNSCC) are in advanced stages, and thus require surgery followed by chemoradiotherapy, locoregional radiotherapy, or concurrent chemoradiotherapy. If the surgical procedure is too invasive, chemoradiotherapy is used first. The multimodality approach has improved quality of life in patients with advanced-stage disease, but prognostic factors remain unclear and unresolved. The failure rate after concurrent chemoradiotherapy ranges between 15% and 50% (26). Despite extensive research on prognostic biomarkers, high-risk factors for recurrence were never identified or resolved in any of the molecular studies (23). Improved outcomes have resulted from advancements in intensity-modulated radiation therapy or hyper-fractionated accelerated treatment regimens. However, the tumour response to radiotherapy varies between patients. Because one-third of patients do not respond to radiotherapy, the appropriate treatment modality for each patient must be determined based on tumour characteristics to improve survival rates (27). Further research into molecular biomarkers may reveal biological differences between oral cancers and predict patient outcomes (28). According to [PERSON] et al., a study was conducted on 105 patients treated with chemoradiotherapy to examine p53 and Ki-67 expression as predictors of tumour recurrence, organ preservation, and survival. The final response in the primary site and neck regions was assessed after 6 to 8 weeks, followed by immunohistochemical (IHC) staining. The study showed a negative association between p53 expression and tumour recurrence, and a lower overall survival rate was correlated with Ki-67 expression. Furthermore, the p53-/Ki-67+ combination predicted a lower frequency of tumour recurrence, a lower risk of second primary cancer, and a higher likelihood of organ preservation [22]. According to [PERSON] et al., a study was conducted to assess the therapy response and survival in cancer patients treated with CRT by evaluating the IHC expression of p53, p27, p21, Ki67, and cyclin D1. The study included 111 patients with oral and oropharyngeal SCC (stages II-IV). The margins were evaluated after surgical resection and found to be negative. IHC staining was performed to demonstrate the markers' prognostic value. The findings revealed that the biomarkers had no effect on the chemoradiation response and were not related to overall survival outcomes. The nodal stage, TNM stage, tumour response, chemoradiation response, and perineural invasion, on the other hand, had a significant association [18]. [PERSON] et al. studied cyclin D1 expression in 97 (stage III-IV) OSCC patients undergoing chemotherapy. The findings revealed that cyclin D1 overexpression and positive lymph node status were poor predictors of treatment response in patients with locally advanced oral cancer. Treatment response decreases as cyclin D1 expression increases. The clinicopathologic factors that show a significant and positive correlation with mean cyclin D1 expressions are tumour size, lymph node status, and clinical stage [19]. [PERSON] et al. conducted a study to assess the relationship of EGFR and p53 expression with survival, tumour response, and quality of life (QOL) in 120 patients with (stage III-IV) OSCC undergoing CRT. Overexpression of p53 was linked to poor survival, and the overexpression of both p53 and EGFR markers were linked to poor chemoradiation response and low QOL. [PERSON] et al.