Head and neck squamous cell carcinoma (HNSCC) primarily arises from the mucosal epithelium in the oral cavity, pharynx, and larynx. These cancers are often associated with tobacco consumption, alcohol abuse, or both, while HPV infection, primarily HPV-16, is a significant risk factor for oropharyngeal cancers. HNSCC can be categorized into HPV-negative and HPV-positive subtypes, with the latter showing a more favorable prognosis. Traditional staging systems have been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment typically involves multimodal approaches, including surgery, chemoradiotherapy, and the use of targeted therapies such as cetuximab for HPV-negative cancers. Immune checkpoint inhibitors like pembrolizumab and nivolumab have been approved for recurrent or metastatic HNSCC. Ongoing research aims to identify predictive biomarkers to improve treatment outcomes. HNSCC is the sixth most common cancer globally, with incidence rates expected to rise by 30% by 2030. Risk factors include tobacco and alcohol consumption, environmental pollutants, and viral infections. The disease progresses through a series of histological stages, from hyperplasia to dysplasia, carcinoma in situ, and invasive carcinoma. Genetic and epigenetic alterations, as well as dysregulation of signaling pathways, play crucial roles in the development and progression of HNSCC. The tumor microenvironment, including immune cells and fibroblasts, contributes to tumor growth and immune evasion. Metastasis is facilitated by mechanisms such as epithelial-mesenchymal transition (EMT) and the production of matrix metalloproteinases (MMPs). Early diagnosis and prevention strategies are essential, with symptoms varying depending on the anatomical site and etiology of the tumor.Head and neck squamous cell carcinoma (HNSCC) primarily arises from the mucosal epithelium in the oral cavity, pharynx, and larynx. These cancers are often associated with tobacco consumption, alcohol abuse, or both, while HPV infection, primarily HPV-16, is a significant risk factor for oropharyngeal cancers. HNSCC can be categorized into HPV-negative and HPV-positive subtypes, with the latter showing a more favorable prognosis. Traditional staging systems have been supplemented by the 2017 AJCC/UICC staging system, which incorporates additional information relevant to HPV-positive disease. Treatment typically involves multimodal approaches, including surgery, chemoradiotherapy, and the use of targeted therapies such as cetuximab for HPV-negative cancers. Immune checkpoint inhibitors like pembrolizumab and nivolumab have been approved for recurrent or metastatic HNSCC. Ongoing research aims to identify predictive biomarkers to improve treatment outcomes. HNSCC is the sixth most common cancer globally, with incidence rates expected to rise by 30% by 2030. Risk factors include tobacco and alcohol consumption, environmental pollutants, and viral infections. The disease progresses through a series of histological stages, from hyperplasia to dysplasia, carcinoma in situ, and invasive carcinoma. Genetic and epigenetic alterations, as well as dysregulation of signaling pathways, play crucial roles in the development and progression of HNSCC. The tumor microenvironment, including immune cells and fibroblasts, contributes to tumor growth and immune evasion. Metastasis is facilitated by mechanisms such as epithelial-mesenchymal transition (EMT) and the production of matrix metalloproteinases (MMPs). Early diagnosis and prevention strategies are essential, with symptoms varying depending on the anatomical site and etiology of the tumor.