The Role of HPV and Smoking in the Development of Squamous Cell Carcinoma of the Head and Neck: A Systematic Review of Molecular and Genetic Mechanisms

Introduction: Head and neck squamous cell carcinoma (HNSCC) has become the sixth most common cancer worldwide, with an increasing incidence rate. Infection with human papillomavirus (HPV) and tobacco use are two primary factors contributing to the development of this disease. Therefore, this study aims to review the molecular and genetic mechanisms underlying their association with HNSCC. Search Strategy: The present study is a systematic review conducted by searching Google Scholar and Elmnet, as well as databases including the Scientific Information Database, Magiran, PubMed and Science Direct, using keywords such as Head and Neck Squamous Cell Carcinoma, Human Papillomavirus Virus, Mutations, Smoking and Tumor Suppressor Gene within the time frame of ۲۰۰۰ to ۲۰۲۴. Out of the articles found, ۲۴ studies were selected and reviewed based on the research objectives. Articles that were inaccessible or irrelevant were excluded, resulting in a final selection of ۱۸ articles for evaluation. Results: Studies indicate that HPV and smoking play roles in the development of Head and neck squamous cell carcinoma (HNSCC) through different molecular mechanisms. In smokers, carcinogenic chemicals in tobacco, such as polycyclic aromatic hydrocarbons and nitrosamines, are released during high-temperature combustion. These substances can cause mutations in the P۵۳ gene, a tumor suppressor. Such mutations may lead to the deletion of the ۹p۲۱-۲۲ region and loss of function of the P۱۶ (CDKN۲A) gene, contributing to uncontrolled cell growth and cancer onset. In HPV infections, particularly high-risk types ۱۶ and ۱۸, the E۶ and E۷ proteins inactivate the P۵۳ and Rb genes, respectively. The E۶ protein degrades P۵۳, while E۷ inactivates Rb, disrupting the cell cycle. These alterations activate signaling pathways like PI۳K/AKT and MAPK, facilitating the growth and survival of cancerous cells. Conclusion and Discussion: Cancer is recognized as a genetic disease resulting from the dysfunction of genes. Given the importance of advancements in targeted therapies, it is recommended that a deeper understanding of the molecular and genetic mechanisms be pursued to enhance and advance therapeutic approaches in this field.

کلیدواژه ها:

Head and Neck Squamous Cell Carcinoma ، Human Papillomavirus ، Mutations ، Smoking ، Tumor Suppressor Gene