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.

Mitochondria-Related TFAM and POLG Gene Variants and Associations with Tumor Characteristics and Patient Survival in Head and Neck Cancer.

In 2020, 878,348 newly reported cases and 444,347 deaths related to head and neck cancer were reported. These numbers suggest that there is still a need for molecular biomarkers for the diagnosis and prognosis of the disease. In this study, we aimed to analyze mitochondria-related mitochondrial transcription factor A (TFAM) and DNA polymerase γ (POLG) single-nucleotide polymorphisms (SNPs) in the head and neck cancer patient group and evaluate associations between SNPs, disease characteristics, and patient outcomes. Genotyping was performed using TaqMan probes with Real-Time polymerase chain reaction. We found associations between TFAM gene SNPs rs11006129 and rs3900887 and patient survival status. We found that patients with the TFAM rs11006129 CC genotype and non-carriers of the T allele had longer survival times than those with the CT genotype or T-allele carriers. Additionally, patients with the TFAM rs3900887 A allele tended to have shorter survival times than non-carriers of the A allele. Our findings suggest that variants in the TFAM gene may play an important role in head and neck cancer patient survival and could be considered and further evaluated as prognostic biomarkers. However, due to the limited sample size (n = 115), further studies in larger and more diverse cohorts are needed to confirm these findings.

Exploring the feasibility of smart phone microphone for measurement of acoustic voice parameters and voice pathology screening.

The objective of this study is to evaluate the reliability of acoustic voice parameters obtained using smart phone (SP) microphones and investigate the utility of use of SP voice recordings for voice screening. Voice samples of sustained vowel/a/obtained from 118 subjects (34 normal and 84 pathological voices) were recorded simultaneously through two microphones: oral AKG Perception 220 microphone and SP Samsung Galaxy Note3 microphone. Acoustic voice signal data were measured for fundamental frequency, jitter and shimmer, normalized noise energy (NNE), signal to noise ratio and harmonic to noise ratio using Dr. Speech software. Discriminant analysis-based Correct Classification Rate (CCR) and Random Forest Classifier (RFC) based Equal Error Rate (EER) were used to evaluate the feasibility of acoustic voice parameters classifying normal and pathological voice classes. Lithuanian version of Glottal Function Index (LT_GFI) questionnaire was utilized for self-assessment of the severity of voice disorder. The correlations of acoustic voice parameters obtained with two types of microphones were statistically significant and strong (r = 0.73-1.0) for the entire measurements. When classifying into normal/pathological voice classes, the Oral-NNE revealed the CCR of 73.7% and the pair of SP-NNE and SP-shimmer parameters revealed CCR of 79.5%. However, fusion of the results obtained from SP voice recordings and GFI data provided the CCR of 84.60% and RFC revealed the EER of 7.9%, respectively. In conclusion, measurements of acoustic voice parameters using SP microphone were shown to be reliable in clinical settings demonstrating high CCR and low EER when distinguishing normal and pathological voice classes, and validated the suitability of the SP microphone signal for the task of automatic voice analysis and screening.

Correlation between the basic video laryngostroboscopic parameters and multidimensional voice measurements.

OBJECTIVE: The aim of this study is to evaluate the correlations among the basic video laryngostroboscopic (VLS) parameters and vocal function assessed using a multidimensional set of perceptive, acoustic, aerodynamic, and subjective measurements. METHODS: Digital VLS recordings and multidimensional voice assessment were performed for 108 individuals, namely 26 healthy and 82 patients with mass lesions of vocal folds and paralysis. The VLS variables (glottal closure, regularity, mucosal wave on the affected/healthy side, symmetry of vibration, and symmetry of image) were rated and quantified on a visual analog scale. Correlations among the VLS parameters and results of acoustic voice analysis and voice range profile (VRP), data of subjective (voice handicap index [VHI] and glottal function index [GFI]), perceptual (G-grade, R-roughness, B-breathiness, A-asthenic scale), and dysphonia severity index (DSI) measurements were tested using Pearson's correlation coefficient. RESULTS: The intercorrelations of VLS parameters in vocal performance were moderate to strong and statistically significant for the entire functional measurements obtained through different modalities. The definitive correlations between VLS and VRP parameters were as follows: r=0.69-0.79 for normal profile coverage, r=0.67-0.76 for dynamic intensity, and r=0.67-0.74 for maximum intensity. All VLS parameters correlated moderately with VHI, GFI, and DSI (r=0.5-0.65, r=0.4-0.57, and r=0.61-0.69, respectively). The strongest correlations were found between VLS parameters and G factor of the GRBA scale (r=0.68-0.88). CONCLUSIONS: Correlation analysis of the vibratory pattern of the vocal folds obtained via VLS provides more comprehensive insight into the pathophysiology of phonation and suggests the documented and measurable evidence of complex mechanisms of vocal outcome.

Quantitative evaluation of video laryngostroboscopy: reliability of the basic parameters.

OBJECTIVE: The purpose of this study was to evaluate quantitatively the basic parameters of the video laryngostroboscopy (VLS) and determine the sensitivity and specificity of these parameters discriminating healthy and pathological voice classes. METHODS: Digital VLS recordings were performed for 159 individuals: 26 healthy and 133 patients. VLS variables (glottal closure, regularity, mucosal wave on the affected/healthy side, symmetry of vibration, and symmetry of image) were rated two times with the time interval of 1 year by three laryngologists. To evaluate interrater and test-retest reliability, intraclass correlation coefficients (ICCs) were calculated. To evaluate sensitivity and specificity of the VLS parameters, discriminant analysis was used. RESULTS: Moderate to almost perfect levels (ICC 0.46-0.90) of interrater reliability were revealed for most of the basic VLS parameters. The ICC of the interrater reliability was highest for symmetry of glottal image; the most problematic VLS parameter for rating was mucosal wave on the healthy side. ICC of the test-retest reliability were 0.71-0.95, P<0.001. An optimum system of VLS parameters discriminating normal and pathological voice subgroups with sensitivity 96.3% and specificity 100% included glottal closure and mucosal wave on the affected side. CONCLUSIONS: The quantitative evaluation of the VLS using basic parameters showed to be reliable in clinical settings and demonstrated high sensitivity and specificity distinguishing healthy and pathological voice patient groups.

Validation of the Lithuanian version of the Glottal Function Index.

OBJECTIVE: To culturally adapt the Glottal Function Index (GFI) questionnaire to the Lithuanian language, and to validate it. METHODS: Psychometric analyses were performed on the translated Lithuanian version of the GFI (GFI-LT) as described by the Scientific Advisory Committee of the Medical Outcomes Trust. The GFI-LT was completed by 50 voice-disordered individuals and by 50 healthy subjects of the control group. Validity, reliability, reproducibility, sensitivity, and responsiveness to clinical change of the GFI-LT were evaluated. To assess the concurrent validity of the GFI-LT, all participants also completed the Voice Handicap Index (VHI) questionnaire. RESULTS: The GFI-LT showed a statistically significantly high reliability and internal consistency (Cronbach α=0.8, r=0.50), and moderate item-total correlation (r=0.41-0.55). Cronbach α coefficients of the test-retest reliability were above the standard (≥0.9) for individuals testing. There was a statistically significant difference between the mean scores of the control and the voice-disordered groups (P<0.001). The Receiver Operating Characteristic test indicated that the GFI-LT score of >3.0 was the optimal score distinguishing patients and healthy controls with the sensitivity of 88% and specificity of 84%. Statistically significant (P<0.05) strong correlations were found between the GFI-LT and VHI scores. The GFI-LT was found to be a responsive measurement instrument to patients' clinical statement; mean difference of the GFI-LT scores in the group of voice-disordered patients before and after surgical treatment was 5.7 (P<0.001). CONCLUSION: The GFI-LT is considered to be a valid and reliable tool for self-assessment of the severity of voice disorders in Lithuanian-speaking patients.