Padervinskis, Evaldas

Laryngeal cancer is a relatively uncommon malignancy with predisposing genetic factors that remain unclear. Single-nucleotide polymorphisms (SNPs) in genes involved in innate immune signaling may contribute to the development and progression of laryngeal carcinoma. This study aimed to evaluate the association of TLR4 (rs7037225, rs11536889, rs7037117) and MYD88 (rs7744, rs6853) polymorphisms with the risk of laryngeal squamous cell carcinoma (LSCC), as well as its clinical and pathological characteristics and survival. A retrospective case–control study involving 172 LSCC patients and 220 healthy controls was conducted. Genotyping was performed using real-time PCR from venous blood samples. MYD88 rs7744 was significantly associated with tumor size and lymph node involvement. Survival analysis showed a significant association between rs7744 and recurrence-free survival (RFS), with the AG and GG genotypes linked to poorer outcomes. Conversely, carriers of the TLR4 rs7037225 CT genotype showed significantly improved RFS, with p ranging from 0.024 to 0.037 across models. Considering the significant roles of TLR4 and MYD88 in Toll-like receptor signaling, these findings may reflect the involvement of innate immune pathways in LSCC progression. In summary, MYD88 rs7744 was associated with clinicopathological features and RFS, while TLR4 rs7037225 appeared to have a potential protective effect on survival.

Background and Objectives Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare but aggressive head and neck malignancy, characterized by poor prognosis and low survival rates. Despite advances in treatment, the molecular mechanisms underlying HSCC development and progression remain misunderstood. The MYD88 gene, which encodes a crucial adaptor protein in innate immune signaling pathways, and its dysregulation have been linked to oncogenesis across many tumor types. However, the role of MYD88 genetic variants in HSCC has not been thoroughly investigated. Material and Method This retrospective case–control study was conducted in the Lithuanian University of Health Sciences, Department of Otorhinolaryngology, between 2017 and 2024, including 79 male patients with histologically confirmed HSCC and 220 healthy male controls. Clinical and pathological data were collected from medical records. Genomic DNA was extracted from peripheral blood samples, and selected MYD88 polymorphisms (rs7744 and rs6853) were genotyped using real-time PCR with TaqMan probes in the Oncology Research Laboratory, Institute of Oncology. Statistical analyses were performed using SPSS (version 30.0). Results The MYD88 rs7744 polymorphism was significantly associated with distant metastasis. Carriers of the GG genotype had a markedly increased risk compared to AA genotype carriers (OR = 28.46, 95% CI: 1.85–438.82, p = 0.016). No significant associations were observed between MYD88 polymorphisms and HSCC susceptibility, relapse-free survival, or overall survival. Additionally, rs6853 showed no association with clinicopathological features. Conclusions and Recommendations The MYD88 rs7744 variant might play a role in tumor progression, specifically regarding distant metastasis, rather than in susceptibility to HSCC.

Disertaciniame darbe siekta surasti naujus technologinius sprendimus burnos, veido ir žandikaulių (BVŽ) srities navikinės kilmės patologijoms aptikti. Tuo tikslu, įvertintos infraraudonųjų spindulių termografijos (IRST) ir dirbtinio intelekto (DI) taikymo galimybės. Tyrime naudotas optimizuotas k artimiausių kaimynų (kNN) klasterizatorius, apmokytas pagal specialiai atrinktus aštuonis temperatūrinius požymius, o rezultatai validuoti naudojant kompiuterinės tomografijos (KT) ir magnetinio rezonanso tomografijos (MRT) tyrimų duomenis. Atlikti tyrimai parodė, kad IRST gali patikimai aptikti patologinius pokyčius (navikinės ar uždegiminės kilmės) BVŽ srityje ir gauti rezultatai gerai sutapo su KT / MRT duomenimis. Atrinkti temperatūriniai požymiai, dalis kurių pasižymėjo aukšta diferenciacine verte, sudarė pagrindą sėkmingam kNN klasterizatoriaus taikymui skirstant pacientų termovaizdus į sveikus ir patologinius atvejus. Optimizuotas kNN modelis pasiekė 90–98 % tikslumą, jautrumą ir specifiškumą. Dirbtinio intelekto ir IRST technologijų taikymas, validuotas radiologinių tyrimų duomenimis, leidžia pagrįstai įvertinti optimizuoto metodo veiksmingumą bei atskleidžia jo potencialą taikyti klinikinėje praktikoje pacientų srautų pirminiam rūšiavimui.

Background and Objectives Head and neck cancer is the 6th most common cancer worldwide. This is a large group of cancers that are different in their representation, aggressiveness and outcomes. Laryngeal squamous cell carcinoma (LSCC) accounts for 30-40 % and hypopharyngeal squamous cell carcinoma (HSCC) for around 3-5 % of head and neck cancers. Though there are a few known risk factors of these diseases, most notably alcohol and tobacco consumption, only a small number of patients that are exposed are diagnosed with these cancers. This suggest that there is individual genetic predisposition to the disease, although the genetic biomarkers are yet to be discovered. One of the target genes of Notch signaling pathway, a process which is linked with tumor formation, is HESR family genes, including HEYL gene. Some studies suggest HEYL gene and its single nucleotide polymorphisms (SNPs) to have association with risk of various cancers, though its impact on head and neck cancers remains unclear. The objective of this study was to evaluate the association between selected single nucleotide polymorphisms HEYL rs41264499 and rs11206478 and risk of LSCC and HSCC; secondly, the objective was to assess if there is a link between HEYL selected SNPs and LSCC as well as HSCC pathomorphological characteristics. Material (patients) and research method used Two groups, consisting of 251 male patients were included in this retrospective casecontrol study study: 79 male patients with diagnosed hypopharyngeal squamous cell carcinoma and 172 male patients with diagnosed laryngeal squamous cell carcinoma. There was a control group of 220 healthy male individuals included during their routine annual health checkup at the family doctor in Kaunas Clinics. The study was approved by the Kaunas Regional Biomedical Research Ethics Committee (Protocols No. BE-2- 37, No. BE-2-10, and No. P1-BE-2-10/2014.). Data was collected on tumor size, lymph node involvement, extranodular extention, distant metastasis, stage, histological grade and association with HPV infection. DNA was extracted from peripheral venous blood samples of all individuals using a commercial DNA extraction kit (Thermo Fisher Scientific Baltics) as indicated on the manufacturer's guidelines. Genotyping of the selected polymorphisms HEYL rs41264499 and rs11206478 was performed using TaqMan® SNP Genotyping Assays on the QuantStudio™ 3 Real-Time PCR System. Statistical analysis was performed using IBM SPSS Statistics for Windows, v. 25.0. Findings/results in sufficient details to support conclusions In this study we determined that the HEYL rs41264499 CG genotype carriers had a 1.874-fold increased risk of LSCC (OR = 1.874, CI 95% (1.057-3.323), p = 0.031). Additionally, we found that the distribution of HEYL rs41264499 G allele carriers and non-carriers is statistically significantly different in patients with LSCC compared to the control group (p = 0.030). The binary logistic regression analysis showed that the G allele carriers of HEYL rs41264499 had an increased risk of LSCC (OR = 1.838, CI 95% (1.055-3.203), p = 0.032). No clear link was found between HEYL rs11206478 and risk of LSCC. Both of the selected polymorphisms showed no association on risk of HSCC. In addition, there was no significant association between selected HEYL SNPs and tumor size, lymph node involvement, metastasis, stage, histological grade, HPV infection and extranodular extention. Conclusions and recommendations HEYL rs41264499 CG genotype carriers as well as G allele carriers in the allelic model had an increased risk of developing laryngeal squamous cell carcinoma. There was no association between selected SNPs and laryngeal and hypopharyngeal cancer pathomorphological features. Study results suggest that HEYL rs41264499 may have a value in determining risk of LSCC.

Background: Laryngeal squamous cell carcinoma (LSCC) is the most common cancer of the head and neck region. Despite the great research effort, the role of potential behavioral and genetic risk factors remains unclear. Therefore, it is essential to search for genetic factors that could contribute to earlier diagnostics and help improve patient survival. Material and Methods: 172 men with diagnosed LSCC were enrolled in this retrospective case-control study with the control group of 220 healthy men. Genomic DNA was extracted from EDTA-preserved peripheral venous blood samples from all individuals. Genotyping of selected polymorphisms HEYL rs41264499 and rs11206478, HEY1 rs2467789 and rs1046472 using real-time PCR was performed at the Oncology Research Laboratory of Oncology Institute at the Lithuanian University of Health Sciences. Statistical data analysis was performed using SPSS v29.0. Results: Our study results show that the HEYL rs41264499 CG genotype carriers had a 1.874-fold increased risk of LSCC (OR = 1.874, CI 95% (1.057-3.323), p = 0.031). Also, it was determined that the G allele carriers of HEYL rs41264499 had an increased risk of LSCC (OR = 1.838, CI 95% (1.055-3.203), p = 0.032). Further, HEY1 rs1046472 TT genotype carriers (compared to GG genotype) had an increased odds of LSCC by 2.527-fold (OR=2.527, 95% CI (1.028-6.212), p = 0.043). HEY1 rs1046472 G allele carriers had a reduced likelihood of LSCC compared to the control group (OR = 0.395, 95% CI (0.163-0.955, p = 0.039). Conclusion: HEYL rs41264499 and HEY1 rs1046472 polymorphisms have significant association with LSCC development.

Background and Objectives The incidence rate of head and neck cancer is increasing annually. Laryngeal and hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively) are mostly diagnosed at late stages, and the mortality rate of these diseases remains high. Metastasis is the most common cause of mortality in cancer patients. One of the key mechanisms involved in metastasis formation is epithelial mesenchymal transition (EMT). HEY1, a target gene of EMT, along with its single nucleotide polymorphisms (SNPs) has shown to have association with increased risk of various types of cancers. However, there has not been enough research on HEY1 gene and its impact on head and neck cancer. Investigating novel genetic biomarkers is vital for enhancing earlier diagnostics and improving patient survival. The objective of this study was to explore the impact of HEY1 selected single nucleotide polymorphisms and risk of disease as well as clinical features of LSCC and HSCC. Material and Method A total of 172 male patients with diagnosed LSCC and 79 male patients with diagnosed HSCC were included in this retrospective case-control study. The control group consisted of 220 healthy men. Information from medical patient history files on tumor size, stage, lymph node involvement, association with HPV infection and histological grade was collected. DNA was extracted from peripheral venous blood samples using a commercial DNA extraction kit (Thermo Fisher Scientific Baltics, Vilnius, Lithuania) according to the manufacturer's protocol. Genotyping of the selected polymorphisms was performed using TaqMan® SNP Genotyping Assays (Applied Biosystems Europe BV, UK Branch, Warrington, Cheshire, UK) on the QuantStudio™ 3 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA). Statistical analysis was conducted using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA). The study was approved by the Kaunas Regional Biomedical Research Ethics Committee (Protocols No. BE-2-37, No. BE-2-10, and No. P1-BE-2-10/2014.) Results Our study results indicate a significant association between HEY1 rs1046472 and elevated risk of LSCC. HEY1 rs1046472 TT genotype carriers (compared to the GG genotype) had an increased odds of LSCC by 2.527-fold (OR=2.527, 95% CI 1.028- 6.212, p = 0.043). HEY1 rs1046472 G allele carriers had a reduced likelihood of LSCC compared to the control group (OR = 0.395, 95% CI 0.163-0.955, p = 0.039. Moreover, HEY1 rs2467789 did not have a significant impact on risk of LSCC. There was no significant association between both selected polymorphisms and risk of HSCC. Furthermore, no clear link was found between selected polymorphisms and clinical as well as pathological features of both LSCC and HSCC. Conclusion and recommendations HEY1 rs1046472 TT genotype carriers had an increased risk of developing laryngeal cancer. There was no association between selected polymorphisms and laryngeal and hypopharyngeal cancer clinical as well as pathological features. According to these findings, rs1046472 might be a useful genetic indicator of LSCC risk.

Objective. The present study aimed to evaluate the effectiveness of the performance of an AI-driven SpeechEnhancer algorithm speech synthesis following laryngeal oncosurgery.

Objective: This study aimed to assess the diagnostic value of contrast-enhanced ultrasound (CEUS) time–intensity curve (TIC) parameters in detecting non-ossified thyroid cartilage invasion in patients with laryngeal squamous cell carcinoma (SCC). Methods: A CEUS TIC analysis was performed on 32 cases from 27 patients with histologically confirmed laryngeal SCC. The diagnostic performance of time to peak (TTP), peak intensity (PI), wash-in slope (WIS), area under the curve (AUC), and their quantitative differences (∆TTP, ∆PI, ∆WIS, and ∆AUC) to discriminate between the invaded and the non-invaded non-ossified thyroid cartilage was determined using ROC analysis. A logistic regression analysis was employed to identify significant predictors. Results: In an ROC analysis, of all TIC parameters analyzed separately, ∆TTP showed the greatest diagnostic performance (AUC: 0.85). A ∆TTP cut-off of ≤ 8.9 s differentiated between the invaded and the non-invaded non-ossified thyroid cartilage with a sensitivity of 100%, specificity of 76.9%, and accuracy of 81.3%. A combination of ∆TTP and PI increased the AUC to 0.93, specificity to 100%, and accuracy to 96.8%, but reduced the sensitivity to 83.3%. Meanwhile, the visual assessment of enhancement on CEUS to detect cartilage invasion had 83.3% sensitivity and 84.6% specificity. In a univariate logistic regression, only ∆TTP was a significant predictor of non-ossified thyroid cartilage invasion (OR: 0.80; 95% CI: 0.64–1.00). For every second increase in ∆TTP, the probability of thyroid cartilage invasion decreased by 20%. Conclusions: CEUS TIC parameters, particularly a combination of ∆TTP and PI, showed high diagnostic performance in the detection of non-ossified thyroid cartilage invasion in laryngeal SCC.

Introduction Head and neck cancer is the third most common cancer worldwide, and despite the advances in treatment, the mortality remains high (1). Identifying genetic factors that contribute to disease pathogenesis and patient survival remains essential. HEY2 gene promotes epithelial-mesenchymal transition, a process linked with metastasis formation which is the leading cause of mortality in cancer patients. HEY2 has shown to have prooncogenic role in studies with hepatocellular carcinoma, non-small cell lung cancer and ovarian cancer (2-4). However, there are no studies on HEY2 significance in laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) development. Aim To evaluate the role of selected HEY2 gene polymorphisms in the development, differentiation, and risk of metastasis of LSCC and HSCC. Methods A total of 172 men with LSCC and 79 men with HSCC were enrolled in this retrospective case-control study, with a control group of 220 healthy men. Women were excluded from this study due to much higher prevalence of LSCC and HSCC in men and limited amount of cases yearly (5). Genomic DNA was extracted from peripheral venous blood samples collected from all individuals. Genotyping of selected HEY2 rs3734637 and rs6940469 polymorphisms was performed using real-time PCR with TaqMan probes. Results Patients with the HEY2 rs3734637 GG genotype had reduced odds of LSCC development compared to those with the TT genotype (OR = 0.545, 95% CI: 0.303–0.980, p = 0.043). This association was also significant in the allelic model, where T allele carriers of HEY2 rs3734637 had a 1.878-fold increased risk of LSCC development compared to non-carriers (OR = 1.878, 95% CI: 1.128–3.126, p = 0.015). Conclusions HEY2 rs3734637 polymorphism TT genotype was associated with increased odds of developing LSCC. There was no statistically significant association between the investigated polymorphisms and the pathomorphological features of HSCC tumors.

Head and neck cancer is the seventh leading cancer diagnosis worldwide. One of the most common cancers in the head and neck region is laryngeal cancer. In past years, the incidence of laryngeal squamous cell carcinoma has risen by 23%, and despite progress in treatment modalities, the survival rate has not changed. It is well known that genetic alterations may contribute to individuals’ susceptibility to cancer. Research of genetic alterations, such as single nucleotide polymorphisms, is essential to understanding carcinogenesis and susceptibility of laryngeal squamous cell carcinoma. A total of 200 LSCC patients and 200 controls were included in this retrospective case-control study; both groups were matched by age and sex. In the present study, we analyzed six SNPs in genes essential for apoptosis regulation: TP53 (rs9895829, rs17884306), BCL2 (rs1564483, rs4987855), BAX (rs704243), NOXA (PMAIP1) (rs1041978, rs78800940). We evaluated their associations with the risk of LSCC development, its pathomorphological manifestation, and patients’ overall survival rate. Genotyping was carried out using RT-PCR. The AG genotype of rs9895829 was more prevalent in controls than in cancer patients, leading to lower susceptibility to LSCC (OR = 0.301; 95%CI 0.096–0.940; p = 0.039). None of the analyzed SNPs showed an association with pathomorphological features of LSCC, but NOXA rs1041978 T allele carriers were found to be diagnosed with LSCC at an older age (OR = 1.962; 95%CI 1.072–3.592; p = 0.031). There was no statistically significant association between investigated SNPs and patient OS. The present study indicates that the AG genotype of rs9895829 provides a protective effect against LSCC development.