The Relationship Between Interferon Status and HPV Infection in Patients with Oral Epithelial Dysplasia: An Observational Study

Background/Objectives: Oral potentially malignant diseases (OPMDs) with signs of epithelial dysplasia are characterized by a high risk of malignancy. However, there are still no algorithms for their early diagnosis and prediction, due to the many possible predisposing factors, including human papillomavirus (HPV) infection and decreased immunity. There is a need to assess the relationship between the manifestations of oral epithelial dysplasia (OED), HPV invasion in the oral cavity, and interferon status to improve the identification and characterization of patients with different degrees of dysplasia. Methods: This study was designed and reported with reference to the STROBE checklist. The study aimed to assess the association between interferon status and HPV invasion in patients with OED. As per the inclusion and exclusion criteria, this observational study included 180 patients with histologically confirmed oral epithelial dysplasia associated with leukoplakia or oral lichen planus. Interferon (IFN) status was assessed by measuring serum interferon activity, spontaneous interferon production, IFN-α/β, and IFN-γ activity in peripheral blood. HPV DNA was detected and genotyped in biopsy specimens using polymerase chain reaction. Results: HPV-positive patients demonstrated significantly lower IFN-α/β and IFN-γ activity compared with HPV-negative patients (p < 0.001). Severe OED was more frequently observed in HPV-positive individuals, whereas mild dysplasia predominated among HPV-negative patients (p < 0.05). Interferon activity progressively decreased with increasing dysplasia severity, with the lowest IFN-α/β and IFN-γ activity detected in patients with severe dysplasia (p < 0.001 and p < 0.05, respectively). A significant positive correlation between IFN-α/β and IFN-γ activity was identified in patients with moderate dysplasia (p = 0.003). Multivariate binary logistic regression analysis demonstrated that HPV positivity (adjusted OR = 4.62, 95% CI: 2.18–9.79; p < 0.001) and reduced IFN-α/β activity (adjusted OR = 1.34 per 10-unit decrease, 95% CI: 1.14–1.58; p < 0.001) were independently associated with severe dysplasia. The multivariable model demonstrated acceptable discriminatory ability for identifying patients with severe dysplasia (AUC = 0.736), with a sensitivity of 89.4% and a specificity of 56.1%. Conclusions: The findings suggest that HPV-associated OED is linked to reduced interferon status, particularly lower IFN-α/β and IFN-γ activity in more severe dysplastic lesions. Combined assessment of interferon status and HPV detection may help identify patients at higher risk of severe OED.