Epidemiology and risk factors for squamous cell carcinoma of the head and neck

Most head and neck cancers develop from the mucosal epithelium and are grouped under the generic name of head and neck squamous cell carcinoma (HNSCC). There were 890,000 new cases and 460,000 deaths from head and neck malignancies in 2018. Men are 2–4 times more at risk to develop HNSCC than women. In Russia, from 2011 to 2021, there was a tendency towards an increase in the absolute number of malignant tumors of the oral cavity and pharynx. On the contrary, the absolute number of detected lip tumors decreased. Risk factors for HNSCC include smoking, alcohol consumption, chewing areca nut products, exposure to environmental pollutants, infection with viral agents such as Epstein–Barr virus (EBV) and human papillomavirus (HPV). Nicotine is known to activate EGFR, ERK, and AKT signaling pathways in oral cancer. Tobacco products such as classic cigarettes and modern smoke-free vaporizers (IQOS) contain other carcinogens besides nicotine: N’-nitrosonornicotine (NNNN), polycyclic aromatic hydrocarbons (PAHs). A study by M. Gormley et al. and В. Reidel suggests that vaping causes pro-inflammatory but immune suppressive changes in the respiratory tract mucosa. The carcinogenic effect of alcohol is largely associated with the intensity rather than the duration of alcohol consumption. For the oral cavity and hypopharynx, the risk leveled off after 4–5 drinks per day. At present, the causal relationship between chronic mechanical trauma, oral mucosal irritation and carcinoma has little evidence. HPV-16 and HPV-18 are most commonly identified in HPV-positive tumors of the oropharynx. Viral carcinogenesis is associated with inactivation of cell cycle-regulating p53 and retinoblastoma proteins. As a result, cells acquire the ability to divide uncontrollably. Individuals infected with EBV have a 2.5-fold higher risk of developing oral squamous cell carcinoma. The EBV viral protein LMP-1 increases the expression of cyclin D1. According to the meta-analysis conducted by Ramos-García et al in 2018, high expression of cyclin D1 (CyD1) is correlated with worse overall and recurrence-free survival, more advanced stage, metastasis to lymph nodes and higher grade of the tumor. Co-infection with EBV and HPV is associated with advanced-stage HNSCC. Reduction of tobacco and alcohol use, anti-HPV and EBV vaccination should help to reduce the incidence of HNSCC.
Keywords: squamous cell carcinoma of head and neck, alcohol consumption, smoke, E-cigarette use, PAH, papillomaviridae, Epstein–Barr virus
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