Alexander Dushkin

Effect of photodynamic therapy on the expression of toll‐like receptor 2, ‐3, ‐4, and ‐8 in the cervical lesions

Abstract Photodynamic therapy (PDT) is a minimally invasive treatment with low systemic toxicity and immunomodulatory effects, increasingly applied in managing HPV‐associated cervical lesions. Toll‐like receptors (TLRs) are critical in regulating immune responses in cervical pathology, yet their dynamics under PDT remain underexplored. This study investigates the effect of PDT on TLR2, TLR3, TLR4, and TLR8 expression in cervical epithelial cells ex vivo, considering lesion severity. The results reveal that TLR8 exhibited the most significant reduction across all groups 2 h after PDT, with the strongest suppression in patients with invasive cervical cancer. TLR4 expression decreased by 24% in HPV‐infected patients and by 71% in those with cervical cancer, highlighting its potential role in modulating the inflammatory microenvironment post‐PDT. TLR3 showed hyperexpression in LSIL and suppression in HSIL/CIN III, although changes were not statistically significant ( p > 0.05). TLR2 expression remained unchanged, likely due to HPV type variability. These findings demonstrate that PDT effectively reduces hyperexpression of TLR8, TLR4, and TLR3 in early‐stage cervical cancer, suggesting their potential as biomarkers for treatment efficacy. Further research incorporating HPV typing and advanced techniques like liquid biopsy is essential to refine our understanding of TLRs in PDT for HPV‐associated cervical lesions.

Subgroup Analysis of TLR2, -3, -4 and -8 in Relation to the Severity of Clinical Manifestations of Cervical HPV Infection

We present the findings of assessing the expression levels of extracellular TLR2 and TLR4 and intracellular TLR3 and TLR8 correlating with the severity of clinical manifestations of HPV infection. A total of 199 women took part in a single-center prospective comparative research study on TLR2, TLR3, TLR4 and TLR8 expression in HPV-related cervical lesions. TLRs’ mRNA expression was analyzed using real-time reverse transcription polymerase chain reaction (RT-PCR). Our results indicate the potential significance of TLR3, TLR4 and TLR8 in responding to HPV infection and its progression to SILs and CC, highlighting the importance of HPV polyinfection in relation to TLR4 and TLR8.

Personalized approach to management of high-grade squamous intraepithelial lesion

Cervical cancer ranks 4th place among malignant neoplasms in the world in 2020. HPV is the main reason for cervical cancer. The «Gold standard» of cervical screening is an «HPV-testing + PAP-test» co-test. The immune system can clear HPV infection. Pathway of cervical cancer development is investigated, but immunity recognition of HPV is still incompletely studied. Toll-like receptors (TLRs) are membrane receptors on the cell membranes and membrane organelles. TLRs ligands could be bacterial, viral pathogens or toxins. When a ligand binds to TLRs, cytokines production is triggered. Chronic inflammation process down-regulates TLRs expression. This helps develop HPV infection. The current paper demonstrates how photodynamic therapy induces TLRs gene expression. A personal approach to estimating photodynamic therapy by an innate immune response in a clinical case is described. A 43-year-old woman with high-grade squamous intraepithelial lesion and 33rd type of HPV infection turned into a private clinic. The patient had complex check-ups before we defined a treatment strategy. Photodynamic therapy was performed as a non-invasive fertility-preserving treatment. We tested TLRs 2/3/4/8 gene expression before and after photodynamic therapy in 2 h, one week and 6-month periods. PDT induces TLRs gene expression in a 6-month period. HPV elimination was achieved. The patient has no atypical cells in liquid-based cytology investigation after PDT.