Treatment of patients with squamous cell oropharyngeal carcinoma is an urgent problem of modern oncology. At the end of the last century, the key role of HPV infection in the development of oropharyngeal cancer was proved, and significant differences in survival rates were demonstrated depending on the status of HPV in the tumor. Undoubtedly, papers presenting a comparative analysis of the clinical course of two biological substypes of the same disease are in demand. A rethinking of the treatment of oropharyngeal cancer patients is now required due to the continued use of a single treatment approach, despite biological differences reflected in the creation of a separate TNM classification for HPV-positive and HPV-negative oropharyngeal cancer. Perhaps a better understanding of the features of clinical treatment and the results of treatment of patients with p16-positive and p16-negative oropharyngeal cancer will allow individualizing treatment tactics in the coming years. This review presents the modern views of domestic and foreign experts on the identified problem and ways of its solution.