Epithelial‑derived head and neck squamous tumourigenesis (Review)

Abstract

Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein‑Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5‑year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.

Keywords: HNSCC; HPV; biomarkers; clinical trials; lncRNAs; miRNAs; oncogenes.

Figure 1.

TNM classification system, a widely used staging for HNSCC; the system denotes the size and extent of the tumour. T signifies the size and width of the primary tumour, with higher numbers indicating more extensive or deeper growth within the tissue. T1-T4 indicate the size of the primary tumour, with larger numbers signifying greater tumour size area. N indicates the spread of cancer to nearby lymph nodes. N0 denotes the absence of cancer in nearby lymph nodes. N1-N3 indicate the presence of cancer and its size in lymph nodes with cancer. M designation indicates the presence of cancer metastasis, signifying the spread of cancer from the primary tumour to other areas of the body. M0 indicates no spread of cancer, while M1 indicates that the cancer has spread. Also, by using TNM stage system HNSCC can be categorised as stage I, II, III, or IV. The frequency of different types of head and neck cancer has variability depending on its association with HPV. Stage I or II indicates that the cancer is small and has not metastasised from the original site (head and neck cancer). Stage III or IV signifies that the cancer is larger and has spread to other parts of the body.

Figure 2.

Multi-omics approaches available for patients with HNSCC. Genomics includes examining DNA sequences to detect genetic mutations, copy number variations and structural variations that contribute to tumorigenesis. The Transcriptomics approach focuses on the analysis of RNA sequences to explore gene expression patterns, alternative splicing events, and non-coding RNA profiles, offering insights into the functional consequences of genetic alterations. Proteomics entails studying proteins, their structures and functions to uncover post-translational modifications and protein-protein interactions that play crucial roles in cancer pathways. Epigenomics studies modifications such as DNA methylation and histone modifications, which control gene expression without changing the DNA sequence and play a crucial role in the development and progression of HNSCC. Metabolomics analyses all metabolites in the biological sample of HNSCC, offering insight into the metabolic state and changes in metabolic pathways related to this cancer. Microbiomics involves the study of all microbiomes associated with HNSCC, investigating their influence on cancer development and responses to treatment. HNSCC, head and neck squamous cell carcinoma.