Epidemiological studies all over the world demonstrate an increased incidence of head and neck squamous cell carcinoma (HNSCC) associated with human papillomavirus (HPV). The studies have proposed to divide oropharyngeal squamous cell carcinoma into 2 molecular types: HPV-positive and HPV-negative ones with different clinical, morphological, and prognostic characteristics. This is likely to impact on approaches to preventing and treating HNSCC. Objective — to identify human papillomavirus (HPV)-positive HNSCC in the examinees and to establish its clinical, histopathological, and prognostic features. Material and methods. Histological blocks from 42 patients with HNSCC who had been treated in Krasnodar Clinical Oncology Dispensary One in 2011 to 2016 were immunohistochemically tested for the expression of p16INK4a and Ki-67. The results were interpreted using the data of international studies of a correlation between HPV detection and P16 expression, by applying a scoring system according to the degree of staining for p16 (0—4 points). A HPV-positive status was established when p16 overexpression was more than 40% (3 and 4 points); Ki-67 overexpression was determined when staining over 10% of tumor cells. The histopathological characteristics of a tumor and the clinical outcomes of disease were studied. Results. The HPV-positive status was found in 13 (31%) patients with HNSCC. HPV positivity was ascertained to be associated with carcinoma of the palatine tonsils (p=0.006). Women had more commonly a HPV-positive tumor (p=0.032). HPV positivity was characteristic of HNSCC patients younger than 60 years (p=0.043). Unlike the HPV-negative tumor samples, HPV-positive ones were non-keratinizing (p=0.002). The prognostic significance of HPV-positive status was reflected in higher 3-year overall survival (OS) rates (OR, 6.692; 95% CI 1.553—28.832; p=0.003). The 5-year OS rates in HPV-positive HNSCC patients were higher than those in HPV-negative ones (p=0.026). Conclusion. The examinees’ data indicate that the virus plays a significant role in carcinogenesis. There is evidence that it is expedient to divide patients according to the HPV status with different tumor characteristics and disease prognosis.