Molecular Biomarkers of Malignant Transformation in Head and Neck Dysplasia

Abstract

Head and neck squamous cell carcinoma (HNSCC) and its treatments are associated with substantial morbidity, often resulting in cosmetic deformity and loss of physiologic functions including speech and swallowing. Despite advancements in treatment, 5-year survival rates for mucosal malignancies remain below 70%. Effective prevention of HNSCC demands an understanding of the molecular pathways of carcinogenesis. Specifically, defining features of pre-cancerous dysplastic lesions that indicate a better or worse prognosis is necessary to help identify patients who are likely to develop a carcinoma and allow a more aggressive approach to management. There remains a need for identification of biomarkers that can provide both early prognostic and predictive value in clinical decision-making by serving as both therapeutic targets as well as predictors of therapy response. Here, we comprehensively review the most frequently altered molecular biomarkers of malignant transformation in head and neck dysplasia. These markers are involved in a wide range of cellular processes in head and neck carcinogenesis, including extracellular matrix degradation, cell motility and invasion, cell–cell adhesion, solute transport, immortalization, metabolism, the cell cycle and apoptosis, transcription, and cell signaling.

Association of podoplanin expression to histopathological grades of oral epithelial dysplasia and oral squamous cell carcinoma

“…In an attempt to overcome the subjectivity of OED histopathological grading, which frequently fails to predict malignant transformation, efforts have been made to associate particular genetic changes with histomorphological grades. 18 Several studies have proposed PDPN as a marker that has the potential to enhance the diagnosis of OED when combined with histomorphological evaluation. Additionally, PDPN plays a crucial role in assessing the MTP of oral potentially malignant lesions (OPMLs), a determination often elusive through histopathological evaluation alone.…”

Oral Potentially Malignant Disorders: A Comprehensive Review of Diagnostic Approaches and Management Strategies

“…The identification and validation of molecular biomarkers have the potential to improve diagnostic accuracy, risk stratification, and personalized management approaches for patients with OPMDs. 34…”

Serine and one-carbon metabolism sustain non-melanoma skin cancer progression

“…Unlike cSCCs, one of the main factors affecting the low survival rate of HNSCC, is the high percentage of diagnosis at advanced stage, being the recurrence rate of about 50% during the first 2 years from diagnosis. For this reason, several clinical and/or pathological parameters have been indicated to predict prognosis, recurrence, and survival, and to drive the therapeutic choice [31][32][33][34][35][36][37]. Notably, cSCCs and HNSCCs display hallmarks of solid tumors mildly responsive to systemic immunotherapy [38][39][40][41][42][43][44][45].…”