Background: HPV infection has a positive prognostic value in the treatment of patients with oropharyngeal squamous cell carcinoma. The purpose of the study was to evaluate the effect of HPV status on the course of oral cavity cancer. Methods: Formalin-fixed paraffin-embedded tumor tissues were studied in 34 patients with cancer of the floor of the mouth aged 47-85 years, 3 (8.8%) women and 31 (91.2%) men. All patients had histologically verified squamous cell carcinoma: stage (st) I in 1 (2.9%), II st - 8 (23.5%), III st - 12 (35.3%), IV st - 13 (38.3%); G1 in 15 (44.1%), G2 - 19 (55.9%). HPV DNAs were detected by Real-time PCR. Results: HPV DNAs were found in 12 (35.3%) samples of tumor tissues, including type 6 in 1 (2.9%), 11 in 3 (8.8%), 16 in 6 (17.6%), 35 in 1 (2.9%), 16+35 in 1 (2.9%). HPV+ tumors were more often in women (66.7% vs 32.3% in men), but high-risk HPV types were detected in men only - 8 (25.8%). Among patients aged 47-55 years, HPV+ tumor status was detected in 4 (33.3%), 56-65 years in 7 (53.8%), 66 years and older - in 1 (11.1%). In st I, no HPV+ tumors were observed; st II - 3 (37.5%) HPV+ tumors, low-risk in all; st III - 3 (25%) HPV+ patients, including high-risk in 2 (16.7%); st IV - 6 (46.2%) HPV+ samples, high-risk in all. G1 tumors: HPV+ in 7 (46.7%), HPV- in 8 (53.3%) patients; G2 tumors: HPV+ in 5 (26.3%), HPV- in 14 (73.7%) patients. Among patients with HPV+ tumors, metastases were observed in 5 (41.7%), no metastases - in 7 (58.3%); for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. 4 (33.3%) patients with HPV+ tumors died, while 8 (66.7%) survived; for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. Conclusions: The development of squamous cell carcinoma of the oral cavity was multidirectional and depended on the HPV status. HPV+ tumors, especially high-risk ones, were more often registered in stages III and IV. HPV+ tumors were more often lower-grade ones and less often metastasized; the mortality rate among patients with HPV+ tumors was lower than with HPV- ones.