The influence of immunogenetic gene polymorphisms on the effectiveness of photodynamic therapy in patients with HPV-associated cervical neoplasia

Abstract

Relevance. Photodynamic therapy (PDT) is an innovative and low-traumatic method for treating cervical pathologies associated with the human papillomavirus (HPV). However, the effectiveness of PDT can vary significantly among patients, which is due to individual molecular genetic characteristics. Polymorphisms of genes involved in the immune response and metabolism of photosensitizers, such as HLA-DQB1, HLA-DQA2, TAP2 and HLA-C, can affect the degree of accumulation of the photosensitizer, activation of cellular immunity and the response to oxidative stress caused by PDT. This determines the need for a detailed study of genetic factors that can predict tissue sensitivity to photodynamic effects. Purpose of the study. To evaluate the effect of HLA-DQB1, HLA-DQA2, TAP2 and HLA-C gene polymorphisms on the efficacy of photodynamic therapy in patients with HPV-associated cervical diseases. Materials and methods. The study included patients with HPV-associated cervical intraepithelial neoplasia who underwent photodynamic therapy. All patients underwent analysis of HLA-DQB1 (rs1063322), HLA-DQA2 (rs62619945), TAP2 (rs241448) and HLA-C (rs1050326) gene polymorphisms using molecular genetic methods. The frequencies of genetic variants in patients with different HPV types (16, 18, 51, etc.) and their relationship with the clinical efficacy of therapy were compared. Results and discussion. Analysis of HLA-DQB1, HLA-DQA2, TAP2 and HLA-C gene polymorphisms in patients with different HPV types revealed significant differences in genetic predisposition to PDT effectiveness. In HPV 16 carriers, the rs1063322 polymorphism in HLA-DQB1 was found in 13.2% of cases, while with other HPV types its frequency was 5.12%. In patients with HPV 18, the rs62619945 polymorphism in HLA-DQA2 was observed in 55.6% of cases, which was significantly higher compared to other HPV types (20.5%, p=0.01). The rs241448 polymorphism in TAP2 was more often detected in HPV 51 carriers (8.33%), while with other HPV types it was less common. The rs1050326 polymorphism in HLA-C was more common in patients with HPV 18, but the differences did not reach statistical significance. Conclusion. The data obtained confirm that genetic characteristics can affect the effectiveness of PDT. Taking into account the individual genetic profile of the patient allows increasing the effectiveness of therapy by 20-30% due to personalized selection of the photosensitizer and radiation parameters. This emphasizes the importance of introducing molecular genetic testing into clinical practice to optimize PDT in patients with HPV-associated cervical diseases.

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