The association of E2F1 and E2F2 single nucleotide polymorphisms with laryngeal squamous cell carcinoma pathomorphological features.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common types of cancer in the upper respiratory tract. It is well-known that it has a high mortality rate and poor prognosis in advanced stages. There are well-known risk factors for LSCC, though new specific and prognostic blood-based markers for LSCC development and prognosis are essential. The current study aimed to evaluate the impact of four different single nucleotide polymorphisms (SNPs), E2F1 (rs3213183 and rs3213180) and E2F2 (rs2075993 and rs3820028), on LSCC development, morphological features, and patient 5-year survival rate. METHODS: A total of 200 LSCC patients and 200 controls were included in this study; both groups were matched by age and sex. In the present study, we analyzed four single nucleotide polymorphisms (SNPs) in the genes E2F1 (rs3213183 and rs3213180) and E2F2 (rs2075993 and rs3820028) and evaluated their associations with the risk of LSCC development, its clinical and morphological manifestation, and patients 5-year survival rate. Genotyping was carried out using RT-PCR. RESULTS: None of the analyzed SNPs showed a direct association with LSCC development. E2F2 rs2075993 G allele carriers (OR = 4.589, 95% CI 1.050-20.051, p = 0.043) and rs3820028 A allele carriers (OR = 4.750, 95% CI 1.088-20.736, p = 0.038) had a statistically significantly higher risk for poor differentiated or undifferentiated LSCC than non-carriers. E2F1 rs3213180 GC heterozygotes were found to have a 3.7-fold increased risk for lymph node involvement (OR = 3.710, 95% CI 1.452-9.479, p = 0.006). There was no statistically significant association between investigated SNPs and patient 5-year survival rate. CONCLUSIONS: The present study indicates that E2F2 rs2075993 and rs3820028 impact LSCC differentiation, whereas E2F1 rs3213180 - on lymph node involvement.

Smartphone-Based Voice Wellness Index Application for Dysphonia Screening and Assessment: Development and Reliability.

OBJECTIVE: This study aimed to develop a Voice Wellness Index (VWI) application combining the acoustic voice quality index (AVQI) and glottal function index (GFI) data and to evaluate its reliability in quantitative voice assessment and normal versus pathological voice differentiation. STUDY DESIGN: Cross-sectional study. METHODS: A total of 135 adult participants (86 patients with voice disorders and 49 patients with normal voices) were included in this study. Five iOS and Android smartphones with the "Voice Wellness Index" app installed were used to estimate VWI. The VWI data obtained using smartphones were compared with VWI measurements computed from voice recordings collected from a reference studio microphone. The diagnostic efficacy of VWI in differentiating between normal and disordered voices was assessed using receiver operating characteristics (ROC). RESULTS: With a Cronbach's alpha of 0.972 and an ICC of 0.972 (0.964-0.979), the VWI scores of the individual smartphones demonstrated remarkable inter-smartphone agreement and reliability. The VWI data obtained from different smartphones and a studio microphone showed nearly perfect direct linear correlations (r = 0.993-0.998). Depending on the individual smartphone device used, the cutoff scores of VWI related to differentiating between normal and pathological voice groups were calculated as 5.6-6.0 with the best balance between sensitivity (94.10-95.15%) and specificity (93.68-95.72%), The diagnostic accuracy was excellent in all cases, with an area under the curve (AUC) of 0.970-0.974. CONCLUSION: The "Voice Wellness Index" application is an accurate and reliable tool for voice quality measurement and normal versus pathological voice screening and has considerable potential to be used by healthcare professionals and patients for voice assessment.

Pareto-Optimized Non-Negative Matrix Factorization Approach to the Cleaning of Alaryngeal Speech Signals.

The problem of cleaning impaired speech is crucial for various applications such as speech recognition, telecommunication, and assistive technologies. In this paper, we propose a novel approach that combines Pareto-optimized deep learning with non-negative matrix factorization (NMF) to effectively reduce noise in impaired speech signals while preserving the quality of the desired speech. Our method begins by calculating the spectrogram of a noisy voice clip and extracting frequency statistics. A threshold is then determined based on the desired noise sensitivity, and a noise-to-signal mask is computed. This mask is smoothed to avoid abrupt transitions in noise levels, and the modified spectrogram is obtained by applying the smoothed mask to the signal spectrogram. We then employ a Pareto-optimized NMF to decompose the modified spectrogram into basis functions and corresponding weights, which are used to reconstruct the clean speech spectrogram. The final noise-reduced waveform is obtained by inverting the clean speech spectrogram. Our proposed method achieves a balance between various objectives, such as noise suppression, speech quality preservation, and computational efficiency, by leveraging Pareto optimization in the deep learning model. The experimental results demonstrate the effectiveness of our approach in cleaning alaryngeal speech signals, making it a promising solution for various real-world applications.

Reliability of Universal-Platform-Based Voice Screen Application in AVQI Measurements Captured with Different Smartphones.

The aim of the study was to develop a universal-platform-based (UPB) application suitable for different smartphones for estimation of the Acoustic Voice Quality Index (AVQI) and evaluate its reliability in AVQI measurements and normal and pathological voice differentiation. Our study group consisted of 135 adult individuals, including 49 with normal voices and 86 patients with pathological voices. The developed UPB "Voice Screen" application installed on five iOS and Android smartphones was used for AVQI estimation. The AVQI measures calculated from voice recordings obtained from a reference studio microphone were compared with AVQI results obtained using smartphones. The diagnostic accuracy of differentiating normal and pathological voices was evaluated by applying receiver-operating characteristics. One-way ANOVA analysis did not detect statistically significant differences between mean AVQI scores revealed using a studio microphone and different smartphones (F = 0.759; p = 0.58). Almost perfect direct linear correlations (r = 0.991-0.987) were observed between the AVQI results obtained with a studio microphone and different smartphones. An acceptable level of precision of the AVQI in discriminating between normal and pathological voices was yielded, with areas under the curve (AUC) displaying 0.834-0.862. There were no statistically significant differences between the AUCs (p > 0.05) obtained from studio and smartphones' microphones. The significant difference revealed between the AUCs was only 0.028. The UPB "Voice Screen" application represented an accurate and robust tool for voice quality measurements and normal vs. pathological voice screening purposes, demonstrating the potential to be used by patients and clinicians for voice assessment, employing both iOS and Android smartphones.

The survival rate of laryngeal squamous cell carcinoma: impact of IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532 single nucleotide polymorphisms.

PURPOSE: Results of laryngeal squamous cell carcinoma (LSCC) treatment and the 5 year survival rate of these patients remain poor. To purify therapeutic targets, investigation of new specific and prognostic blood-based markers for LSCC development is essential. METHODS: In the present study, we evaluated five single nucleotide polymorphisms (SNPs): IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532, and determined their associations with the patients' 5 year survival rate. Also, we performed a detailed statistical analysis of different LSCC patients' characteristics impact on their survival rate. RESULTS: Three hundred fifty-three LSCC patients and 538 control subjects were included in this study. The multivariable Cox regression analysis revealed a significant association between patients' survival rate and distribution of IL1RAP rs4624606 variants: patients carrying AT genotype at IL1RAP rs4624606 had a lower risk of death (p = 0.044). Also, it was revealed that tumor size (T) (p = 0.000), tumor differentiation grade (G) (p = 0.015), and IL1RAP rs4624606 genotype (p = 0.044) were effective variables in multivariable Cox regression analysis prognosing survival of LSCC patients. The specific-LSCC 5 year survival rate was 77%. CONCLUSIONS: In summary, our findings indicate that the genotypic distribution of IL1RAP rs4624606 influences the 5 year survival rate of LSCC patients. The results of the present study facilitate a more complete understanding of LSCC at the biological level, thus providing the base for the identification of new specific and prognostic blood-based markers for LSCC development.

An iOS-based VoiceScreen application: feasibility for use in clinical settings-a pilot study.

OBJECTIVES: To elaborate the application suitable for smartphones for estimation of Acoustic Voice Quality Index (AVQI) and evaluate its usability in the clinical setting. METHODS: An elaborated AVQI automatization and background noise monitoring functions were implemented into a mobile "VoiceScreen" application running the iOS operating system. A study group consisted of 103 adult individuals with normal voices (n = 30) and 73 patients with pathological voices. Voice recordings were performed in the clinical setting with "VoiceScreen" app using iPhone 8 microphones. Voices of 30 patients were recorded before and 1 month after phonosurgical intervention. To evaluate the diagnostic accuracy differentiating normal and pathological voice, the receiver-operating characteristic statistics, i.e., area under the curve (AUC), sensitivity and specificity, and correct classification rate (CCR) were used. RESULTS: A high level of precision of AVQI in discriminating between normal and dysphonic voices was yielded with corresponding AUC = 0.937. The AVQI cutoff score of 3.4 demonstrated a sensitivity of 86.3% and specificity of 95.6% with a CCR of 89.2%. The preoperative mean value of the AVQI [6.01(SD 2.39)] in the post-phonosurgical follow-up group decreased to 2.00 (SD 1.08). No statistically significant differences (p = 0.216) between AVQI measurements in a normal voice and 1-month follow-up after phonosurgery groups were revealed. CONCLUSIONS: The "VoiceScreen" app represents an accurate and robust tool for voice quality measurement and demonstrates the potential to be used in clinical settings as a sensitive measure of voice changes across phonosurgical treatment outcomes.

Accuracy of Acoustic Voice Quality Index Captured With a Smartphone - Measurements With Added Ambient Noise.

OBJECTIVE: To evaluate the accuracy of Acoustic Voice Quality Index (AVQI) measures obtained from voice recordings simultaneously using oral and smartphone microphones in a sound-proof room, and to compare them with AVQIs obtained from the same smartphone voice recordings with added ambient noise. METHODS: A study group of 183 subjects with normal voices (n = 86) and various voice disorders (n = 97) was asked to read aloud a standard text and sustain the vowel /a/. The controlled ambient noise averaged at 29.61 dB SPL was added digitally to the smartphone voice recordings. Repeated measures analysis of variances (ANOVA) with Greenhouse-Geiser correction was used to evaluate AVQI changes within subjects. To evaluate the level of agreement between AVQI measurements obtained from different voice recordings Bland-Altman plots were used. RESULTS: Repeated measures ANOVA showed that differences among AVQI results obtained from voice recordings done with oral studio microphone, recordings done with a smartphone microphone, and recordings done with a smartphone microphone with added ambient noise were not statistically significant (P = 0.07). No significant systemic differences and acceptable level of random errors in AVQI measurements of voice recordings made with oral and smartphone microphones (including added noise) were revealed. CONCLUSION: The AVQI measures obtained from smartphone microphones voice recordings with experimentally added ambient noise revealed an acceptable agreement with results of oral microphone recordings, thus suggesting the suitability of smartphone microphone recordings performed even in the presence of acceptable ambient noise for estimation of AVQI.

Accuracy Analysis of the Multiparametric Acoustic Voice Indices, the VWI, AVQI, ABI, and DSI Measures, in Differentiating between Normal and Dysphonic Voices.

The study aimed to investigate and compare the accuracy and robustness of the multiparametric acoustic voice indices (MAVIs), namely the Dysphonia Severity Index (DSI), Acoustic Voice Quality Index (AVQI), Acoustic Breathiness Index (ABI), and Voice Wellness Index (VWI) measures in differentiating normal and dysphonic voices. The study group consisted of 129 adult individuals including 49 with normal voices and 80 patients with pathological voices. The diagnostic accuracy of the investigated MAVI in differentiating between normal and pathological voices was assessed using receiver operating characteristics (ROC). Moderate to strong positive linear correlations were observed between different MAVIs. The ROC statistical analysis revealed that all used measurements manifested in a high level of accuracy (area under the curve (AUC) of 0.80 and greater) and an acceptable level of sensitivity and specificity in discriminating between normal and pathological voices. However, with AUC 0.99, the VWI demonstrated the highest diagnostic accuracy. The highest Youden index equaled 0.93, revealing that a VWI cut-off of 4.45 corresponds with highly acceptable sensitivity (97.50%) and specificity (95.92%). In conclusion, the VWI was found to be beneficial in describing differences in voice quality status and discriminating between normal and dysphonic voices based on clinical diagnosis, i.e., dysphonia type, implying the VWI's reliable voice screening potential.

The Role of ApoE Serum Levels and ApoE Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma.

Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients' five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development.

Lightweight Deep Learning Model for Assessment of Substitution Voicing and Speech after Laryngeal Carcinoma Surgery.

Laryngeal carcinoma is the most common malignant tumor of the upper respiratory tract. Total laryngectomy provides complete and permanent detachment of the upper and lower airways that causes the loss of voice, leading to a patient's inability to verbally communicate in the postoperative period. This paper aims to exploit modern areas of deep learning research to objectively classify, extract and measure the substitution voicing after laryngeal oncosurgery from the audio signal. We propose using well-known convolutional neural networks (CNNs) applied for image classification for the analysis of voice audio signal. Our approach takes an input of Mel-frequency spectrogram (MFCC) as an input of deep neural network architecture. A database of digital speech recordings of 367 male subjects (279 normal speech samples and 88 pathological speech samples) was used. Our approach has shown the best true-positive rate of any of the compared state-of-the-art approaches, achieving an overall accuracy of 89.47%.

Factors Affecting the Lifetime of Third-Generation Voice Prosthesis After Total Laryngectomy.

PURPOSE: The study aimed to evaluate the impact of different variables on the longevity of Voice Prosthesis (VP) in patients after total laryngectomy. PATIENTS AND METHODS: This retrospective cohort study is based on data about a continuous series of 328 third-generation VP, which were implanted between 2016 and 2020. Data about the VP users' age, sex, place of residence, laryngeal tumor stage, neck irradiation, VP size, and the use of Heat and Moisture Exchanger (HME) were obtained and analyzed. The effect of these variables on VP lifetime was determined. RESULTS: The median lifetime of VPs in patients 65 years old and above was 182 days (95% CI 168-196), versus 146 days (95% CI 130-162) (P = 0.033) in patients younger than 65. Neck irradiation was associated with a longer VP median lifetime of 161 days (95% CI 142-180) compared to 126 days (95% CI 100-152) with no prior neck irradiation (P = 0.046). HME usage was associated with significantly increased longevity of VPs: 182 days (95% CI 156-208) with HME and 149 days (95% CI 132-166) without HME usage (P = 0.039). CONCLUSION: The results of the present study suggest that neck irradiation, and routine use of use of HME are positively associated with the longevity of VPs.

Investigation of Relationship Between Auditory-Perceptual Methods and Self-reported Speech Handicap Index in the Assessment of Substitution Voicing.

OBJECTIVE: To assess correlations between auditory-perceptual and self-reported speech evaluation methods for substitution voicing (SV) and to investigate the robustness of these methods in a clinical setting. METHODS: Fifty-nine male patients who underwent laryngeal oncosurgery and 62 healthy male controls were included in this prospective study. Lithuanian versions of the Speech Handicap Index (SHI-LT) and Impression of voice quality (I), Impression of intelligibility (I), Unintended additive Noise (N), Fluency (F), and Quality of Voicing (Vo) scale (IINFVo-LT) were used to assess and compare self-reported and auditory-perceptual evaluations of SV. Speech samples were rated by a panel of experienced raters. RESULTS: The IINFVo-LT revealed good inter-rater reliability (ICC = 0.825) and intrarater reliability over time (ICC = 0.976) when assessing SV. Statistically significant differences (P < 0.05) of the mean scores of IINFVo-LT among the cordectomy, partial laryngectomy (22.52 [SD 9.98]), tracheoesophageal prosthesis (16.92 [SD 10.71]), and control (48.01 [SD 2.88]) groups confirmed the usefulness of IINFVo-LT for SV rating. A moderate negative correlation (r = -0.61; P < 0.001) demonstrated good concurrent validity between the IINFVo-LT and the SHI-LT total scores. A statistically significant, strong, negative correlation (r = -0.74) was obtained between the IINFVo-LT and SHI-LT speech handicap grade (P < 0.001), demonstrating good concurrent validity. CONCLUSION: The combination of IINFVo-LT and SHI-LT represents a potentially valuable and robust tool for evaluating SV and is helpful for assessing the degree of speech abnormality after laryngeal oncosurgery and its impact on patients' quality of life.

Association of SIRT1 single gene nucleotide polymorphisms and serum SIRT1 levels with laryngeal squamous cell carcinoma patient survival rate.

BACKGROUND: SIRT1 is a multifunctional protein, possibly essential in tumorigenesis pathways, which can act both as a tumor promoter and tumor suppressor depending on the oncogenes, specific to particular tumors. Pathogenesis of laryngeal cancer is multifactorial and the association of SIRT1 expression with the clinical characteristics and prognosis of LSCC has not been fully identified. OBJECTIVES: The study aimed to evaluate associations between single gene nucleotide polymorphisms (SNPs) of SIRT1 (rs3818292, rs3758391, and rs7895833), serum SIRT1 levels, and 5-year survival rate in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: The study involved 302 patients with LSCC and 409 healthy control subjects. The genotyping of SNPs was performed using RT-PCR, and serum SIRT1 levels were determined by the ELISA method. RESULTS: Our study found significant differences in genotype distributions of SIRT1 rs3758391 polymorphisms between the study groups. SIRT1 rs3758391 T/T genotype was associated with the increased LSCC development odds (OR = 1.960 95% CI = 1.028-3.737; p= 0.041). Carriers of SIRT1 rs3758391 T/T genotype had statistically significantly increased odds of LSCC development into advanced stages under the codominant and recessive genetic models (OR = 2.387 95% CI = 1.091-5.222; p= 0.029 and OR = 2.287 95% CI = 1.070-4.888; p= 0.033, respectively). There were no statistically significant differences in serum SIRT1 levels between the LSCC and control groups. However, LSCC patients with SIRT1 rs3818292 AG genotype demonstrated a tendency to significantly lower SIRT1 serum levels than controls (p= 0.034). No statistically significant associations between SIRT1 (rs3818292, rs3758391, and rs7895833) SNPs and the 5-year survival rate of LSCC patients were found. CONCLUSION: The present study indicated a statistically significant association between the SIRT1 rs3758391 T/T genotype and increased LSCC development odds. LSCC patients with SIRT1 rs3818292 AG genotype showed a tendency to manifest with lower SIRT1 serum levels. No associations between SIRT1 SNPs and the 5-year survival rate of LSCC patients were detected.

Impaired Subjective Visual Vertical and Increased Visual Dependence in Older Adults With Falls.

Aging affects the vestibular system and may disturb the perception of verticality and lead to increased visual dependence (VD). Studies have identified that abnormal upright perception influences the risk of falling. The aim of our study was to evaluate subjective visual vertical (SVV) and VD using a mobile virtual reality-based system for SVV assessment (VIRVEST) in older adults with falls and evaluate its relationship with clinical balance assessment tools, dizziness, mental state, and depression level. This study included 37 adults >65 years who experienced falls and 40 non-faller age-matched controls. Three tests were performed using the VIRVEST system: a static SVV, dynamic SVV with clockwise and counter-clockwise background stimulus motion. VD was calculated as the mean of absolute values of the rod tilt from each trial of dynamic SVV minus the mean static SVV rod tilt. Older adults who experienced falls manifested significantly larger biases in static SVV (p = 0.012), dynamic SVV (p < 0.001), and VD (p = 0.014) than controls. The increase in static SVV (odds ratio = 1.365, p = 0.023), dynamic SVV (odds ratio = 1.623, p < 0.001) and VD (odds ratio = 1.460, p = 0.010) tilt by one degree significantly related to falls risk in the faller group. Fallers who had a high risk of falling according to the Tinetti test exhibited significantly higher tilts of dynamic SVV than those who had a low or medium risk (p = 0.037). In the faller group, the increase of the dynamic SVV tilt by one degree was significantly related to falls risk according to the Tinetti test (odds ratio = 1.356, p = 0.049). SVV errors, particularly with the dynamic SVV test (i.e., greater VD) were associated with an increased risk of falling in the faller group. The VIRVEST system may be applicable in clinical settings for SVV testing and predicting falls in older adults.

The Role of IL-9 Polymorphisms and Serum IL-9 Levels in Carcinogenesis and Survival Rate for Laryngeal Squamous Cell Carcinoma.

Recent studies have described the dichotomous function of IL-9 in various cancer diseases. However, its function has still not been analysed in laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated five single nucleotide polymorphisms (SNPs) of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) and determined their associations with the patients' five-year survival rate. Additionally, we analysed serum IL-9 levels using an enzyme-linked immunosorbent assay. Three hundred LSCC patients and 533 control subjects were included in this study. A significant association between the patients' survival rate and distribution of IL-9 rs1859430 variants was revealed: patients carrying AA genotype had a higher risk of dying (p = 0.005). Haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) were associated with 47% lower odds of LSCC occurrence (p = 0.035). Serum IL-9 levels were found detectable in three control group subjects (8.99 ± 12.03 pg/mL). In summary, these findings indicate that the genotypic distribution of IL-9 rs1859430 negatively influences the five-year survival rate of LSCC patients. The haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) are associated with the lower odds of LSCC development.

Laryngeal carcinoma experimental model suggests the possibility of tumor seeding to gastrostomy site.

Some studies state that laryngeal squamous cell carcinoma (LSCC) is associated with possible direct tumor cell seeding to percutaneous endoscopic gastrostomy (PEG) site. However, there is a lack of experimental proof that LSCC tumor tissue can adhere and grow in distant sites. Therefore, we aimed to investigate the growth pattern of LSCC implants on chicken embryo chorioallantoic membrane (CAM) and evaluate possible associations between clinical course of the disease and behavior of experimentally implanted LSCC tumors. Our results show that implanted LSCC tissue survives on CAMs in 95% of cases while retaining essential morphologic characteristics and proliferative capacity of the original tumor. We identified the increased CAM vascularization, an infiltrative growth pattern of the implant and formation of distant isolated metastatic nodes on the CAMs. LSCC tumors with worse differentiation degree (G2 or G3) adhered to the experimental CAMs significantly better than G1. These results facilitate the understanding of tumor biology and allow hypothetisezing that dissemination and direct implantation of LSCC cells into the stomal wall during the pull PEG procedure might be possible.

Impact of IL-10 Promoter Polymorphisms and IL-10 Serum Levels on Advanced Laryngeal Squamous Cell Carcinoma and Survival Rate.

BACKGROUND/AIM: Prognosis of advanced stages of laryngeal squamous cell carcinoma (LSCC) remains poor. To clarify therapeutic targets and improve survival rate, identification of new specific and prognostic biomarkers of LSCC is required. The study aimed to evaluate the impact of IL-10:rs1800871, rs1800872, rs1800896 single nucleotide polymorphisms (SNPs), and IL-10 serum levels on LSCC development and determine associations of selected SNPs with patient survival rate. PATIENTS AND METHODS: A total of 300 LSCC patients and 533 controls were included in the study. Genotyping was carried out using RT-PCR; IL-10 serum levels were analyzed by ELISA. RESULTS: Significant associations were identified between IL-10 rs1800871 variants and advanced stage of LSCC patient group in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733; p=0.037). Significant variants of IL-10 rs1800872 were determined in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733, p=0.037). The distribution of IL-10 SNPs genotypes did not impact LSCC patient survival rate (respectively, p=0.952; p=0.952; p=0.991). CONCLUSION: IL-10:rs1800871 and rs1800872 SNPs are associated with advanced stage of LSCC. The genotypic distribution of IL-10 SNPs does not influence the survival rate of LSCC patients.

An Experimental Model of Human Recurrent Respiratory Papillomatosis: A Bridge to Clinical Insights.

OBJECTIVES/HYPOTHESIS: To investigate the growth pattern of recurrent respiratory papilloma (RRP) implants on chicken embryo chorioallantoic membranes (CAMs) and to evaluate possible associations between the clinical course of the disease and the behavior of experimentally implanted RRP tumors. STUDY DESIGN: Experimental study. METHODS: Fresh 172 RRP tissue samples from 12 patients were implanted onto chick embryo CAMs. Morphological and morphometric analysis of the experimental CAM and chorionic epithelium was performed. The microvascular network of the CAM with the RRP implant was investigated under the effect of fluoresceinated anionic dextran. The peculiarities of the clinical course of the disease were evaluated. RESULTS: The implanted RRP tissue samples survived on CAMs in 86% of cases, retaining their essential morphologic characteristics and proliferative capacity of the original tumor. Implants induced thickening of both the CAM and the chorionic epithelium, but none of the RRP implants crossed the basement membrane of the hosting CAM. A "crawling film" of acellular material with newly formed papilloma sprouts located on the outer chorionic epithelium of the CAM was detected. Direct association between a recurrence rate of RRP and the number of newly formed papilloma sprouts around the implanted tumor on CAMs was revealed. CONCLUSION: The chicken embryo CAM-based model is appropriate for investigations of RRP and facilitates the understanding of tumor biology and the clinical course of the disease, thus providing the basis for further research and acceleration of the identification and development of new specific therapeutic compounds that limit the spread and recurrence of RRP. LEVEL OF EVIDENCE: N/A Laryngoscope, 131:E914-E920, 2021.

Association of Leukocyte Telomere Length and Genes Involved in its Regulation With Oral Carcinoma.

BACKGROUND/AIM: This study aimed to determine the relationship between the relative leukocyte telomere length (RLTL) and gene polymorphisms involved in its regulation with the occurrence of oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Patients with OSCC and healthy subjects were examined. Genotyping and RLTL measurement were carried out using rPCR. RESULTS: The OSCC group had longer telomeres than controls (p=0.001). Minor allele T at TERF1rs1545827 may increase RLTL shortening (p=0.047). TNKS2rs10509639 A/G and A/G+G/G genotypes were associated with a 2.6-fold increased odd (p=0.012) and a 2.4-fold increased odd (p=0.019) of RLTL elongation compared to A/A genotype. The A/G genotype was associated with a 2.6-fold increased odd (p=0.011) compared to the A/A+G/G genotypes. Each G allele was associated with a 2.1-fold increased odd of longer RLTL (p=0.036). CONCLUSION: Longer telomeres were found in patients with OSCC than in controls. The TERF1 rs1545827 and the TNKS2 rs10509639 polymorphisms were associated with an increase in RLTL.

Tendencies of FGFR2 rs2981582 polymorphism in patients with oral cancer.

OBJECTIVE: Fibroblast growth factor receptor 2 (FGFR2) is a member of the FGFR family of tyrosine kinase receptors, which via cell growth, invasiveness, motility and angiogenesis contributes to the process of tumorogenesis. A huge interest today is focused on FGFR2 gene polymorphism as it may have a significant impact on the development of various benign and malignant tumors. A case-control study was designed to help determine if FGFR2 gene polymorphism rs2981582 is associated with oral cancer in Lithuanian subjects. METHODS: The study included 35 patients with a diagnosis of oral cancer and 100 healthy subjects as a reference group. DNA samples were extracted from peripheral venous blood. Genotyping of FGFR2 rs2981582 was performed using the real-time polymerase chain reaction method. Statistical analysis was performed using "IBM SPSS Statistics 20.0". RESULTS: It was determined that FGFR2 gene rs2981582 polymorphism has no effect on a development of oral cancer. The analysis of FGFR2 gene polymorphisms did not reveal any differences in the distribution of GG, GA, and AA genotypes between the oral cancer group, and the control group (42.9%, 48.6%, and 8.6% vs. 46%, 37% and 17%, respectively). CONCLUSION: Results of present study showed no association between FGFR2 gene polymorphisms rs2981582 and oral cancer. However, a further study with a larger sample sizes is advisable.