This article presents the results of a clinical and laboratory study devoted to evaluating the significance of detecting human papillomavirus (HPV) types 16 and 18 in patients with precancerous lesions of the oral mucosa. The relevance of the study is обусловлена the growing interest in the role of high-risk HPV types in oropharyngeal carcinogenesis and the need to improve early diagnosis of potentially malignant changes in dental practice. The study was carried out in 2024–2026 as an observational clinical investigation. A total of 20 patients aged 30 to 65 years with clinically diagnosed precancerous diseases of the oral mucosa were examined. All patients underwent clinical examination, assessment of complaints, recording of lesion localization and clinical form, as well as PCR-based HPV testing with genotyping for types 16 and 18. It was established that leukoplakia predominated in the structure of clinical forms, accounting for 60% of cases. The most frequent lesion localization was the lateral surface of the tongue (40%), followed by the buccal mucosa (25%) and the floor of the mouth (20%). HPV 16/18 DNA was detected in 2 out of 20 patients, which amounted to 10% of the study sample. The obtained data indicate that in the studied group HPV 16/18 was not the leading factor in the development of precancerous lesions; however, its detection has clinical significance as an additional criterion of oncological alertness and a basis for more careful follow-up observation. The study emphasizes the expediency of including PCR-based HPV typing in the comprehensive examination of patients with clinically suspicious lesions of the oral mucosa.