Aberrant Epigenetic Regulation in Head and Neck Cancer Due to Distinct EZH2 Overexpression and DNA Hypermethylation.

Enhancer of Zeste homologue 2 (EZH2) overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibition of EZH2 is a potentially effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (p < 0.001) and the methylation index of tumor suppressor genes (p < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (p = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, p < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390⁻3.127; p < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

Site-specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis.

The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer. We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples. CpG island hypermethylation status of the three genes was analyzed using quantitative methylation-specific PCR (Q-MSP). In order to determine the prognostic value of the methylation status of these genes, the associations between methylation index and various clinical characteristics, especially tumor site, were assessed for tumors from patients with HNSCC. The methylation index was positively correlated with female gender (P = 0.008) and disease recurrence (P = 0.01) in oral cancer and human papillomavirus (HPV)-positive (P = 0.004) status and disease recurrence (P = 0.005) in oropharyngeal cancer. Among patients with oral and oropharyngeal cancer, promoter hypermethylation of GAL, GALR1, or GALR2 was statistically correlated with a decrease in disease-free survival (log-rank test, P = 0.036 and P = 0.042, respectively). Furthermore, methylation of GAL, GALR1, or GALR2 exhibited the highest association with poor survival (log-rank test, P = 0.018) in patients with HPV-negative oropharyngeal cancers. As such, GAL and GALR1/2 methylation status may serve as an important site-specific biomarker for prediction of clinical outcome in patients with HNSCC. © 2016 Wiley Periodicals, Inc.

Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.

The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51-6.75 (p = 0.002); 2.24, 1.06-4.76 (p = 0.035); and 2.56, 1.09-6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients.

[The Correlation between the Size of Vocal Polyps, Vocal Nodules and Vocal Dysfunction, before and after Laryngeal Microsurgery].

When we operate on a vocal polyp or a vocal nodule with laryngeal microscopy, we always carefully measure their length and width then multiply the length by the width to get the area. We examined whether there is a correlation between the area of these lesions and the acoustic analysis of voice. Before the surgery and one month post-operation, we checked five acoustic parameters, maximum phonation time (MPT), range of voice, mean air flow rate (MFR) and acoustic analyses (jitter% and shimmer%). By doing this, we could arrive at the improvement rate of each of the five acoustic parameters. We examined whether there was a correlation between the lesion area and acoustic parameters before surgery and the improvement rates of these acoustic parameters. Examinations of polyps showed a correlation between the size and range of voice and Jitter% pre-operation, and showed a correlation between the size and improvement rate of range of voice, MFR, Jitter% and Shimmer% post-operation. On the other hand, examination of nodules showed a correlation only between the size and range of voice pre-operation. Next we examined the correlation between the size and these acoustic parameters in the Elite vocal performer (EVP) group and extra EVP group. In the examinations of polyps, the EVP group showed a lower correlation between the size and acoustic parameters than in the extra EVP group. On the other hand, in the examinations of nodules, correlation between the size and acoustic parameters was low in both the EVP and extra EVP group.

Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells.

Galanin and its receptors, GALR1 and GALR2, are known tumor suppressors and potential therapeutic targets in head and neck squamous cell carcinoma (HNSCC). Previously, we demonstrated that, in GALR1-expressing HNSCC cells, the addition of galanin suppressed tumor proliferation via upregulation of ERK1/2 and cyclin-dependent kinase inhibitors, whereas, in GALR2-expressing cells, the addition of galanin not only suppressed proliferation, but also induced apoptosis. In this study, we first transduced HEp-2 and KB cell lines using a recombinant adeno-associated virus (rAAV)-green fluorescent protein (GFP) vector and confirmed a high GFP expression rate (>90%) in both cell lines at the standard vector dose. Next, we demonstrated that GALR2 expression in the presence of galanin suppressed cell viability to 40-60% after 72 h in both cell lines. Additionally, the annexin V-positive rate and sub-G0/G1 phase population were significantly elevated in HEp-2 cells (mock vs GALR2: 12.3 vs 25.0% (P < 0.01) and 9.1 vs 32.0% (P < 0.05), respectively) after 48 h. These changes were also observed in KB cells, although to a lesser extent. Furthermore, in HEp-2 cells, GALR2-mediated apoptosis was caspase-independent, involving downregulation of ERK1/2, followed by induction of the pro-apoptotic Bcl-2 protein, Bim. These results illustrate that transient GALR2 expression in the presence of galanin induces apoptosis via diverse pathways and serves as a platform for suicide gene therapy against HNSCC.

Tumor suppressor activity and inactivation of galanin receptor type 2 by aberrant promoter methylation in head and neck cancer.

BACKGROUND: There is accumulating evidence that galanin receptors (GALRs) may be tumor suppressors in head and neck squamous cell carcinoma (HNSCC). Promoter methylation status and gene expression were assessed in a large panel of head and neck primary tumors, based on the hypothesis that cytosine-guanine dinucleotide (CpG) hypermethylation might silence the galanin receptor 2 (GALR2) gene. METHODS: GALR2 expression was examined in a panel of cell lines by using quantitative reverse transcription polymerase chain reaction (RT-PCR). The methylation status of the GALR2 promoter was studied using quantitative methylation-specific PCR (Q-MSP). UM-SCC-1 was stably transfected to express GALR2. RESULTS: GALR2 expression was suppressed in UM-SCC cell lines, whereas nonmalignant cell lines exhibited stable expression. GALR2 methylation found in 31 of 100 (31.0%) tumor specimens was significantly correlated with the methylation status of both GALR1 and Galanin. The observed GALR2 promoter hypermethylation was statistically correlated with a decrease in disease-free survival (log-rank test, P=.045). A multivariate logistic-regression analysis revealed a high odds ratio for recurring methylation of GALR2 and the gene pair GALR2 and Galanin, 8.95 (95% confidence interval, 2.29-35.03; P=.024) and 9.05 (95% confidence interval, 1.76-46.50; P=.008), respectively. In addition, exogenous expression of GALR2 suppressed cell proliferation in UM-SCC-1 cells with hypermethylated Galanin and GALR2-proficient cell lines. CONCLUSIONS: Frequent promoter hypermethylation in association with prognosis, and growth suppression after re-expression, supports the hypothesis that GALR2 may act to suppress tumor activity. GALR2 is a potentially significant therapeutic target and prognostic factor for this cancer type.

Botulinum toxin injection for abductor spasmodic dysphonia under cervical ultrasonography guidance.

Ultrasound (US) imaging effectively provides real-time anatomical information for clinical examinations. In otolaryngology, US imaging can visualize laryngeal muscles as well as cervical muscles. Here we present the case where US imaging was used while injecting botulinum toxin (BT) for the treatment of abductor spasmodic dysphonia, which provided definite results. We could visualize not only the injection pathway but also the infiltration of the BT solution into the posterior cricoarytenoid muscles. Therefore, our laryngeal US imaging is useful for both improving the success rate and avoiding injection complications of BT.

One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy.

OBJECTIVE: Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections. STUDY DESIGN: Retrospective study with approval by our Ethics Committee. METHODS: The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection. RESULTS: Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men. CONCLUSIONS: Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men. LEVEL OF EVIDENCE: level 4.

Analysis of Speech Fundamental Frequencies for Different Tasks in Japanese.

PURPOSE: Speech fundamental frequency (SFF) assessment is essential for all dysphonia patients to effectively evaluate the therapeutic effects of voice therapy, especially in patients with disturbances in their voice pitch due to mutational dysphonia, Reinke's edema, or as side effects of hormone therapy. A standard method of SFF measurement remains unknown. Speech tasks such as sustained vowel phonation, counting, reading passage, and spontaneous speech have generally been used for SFF measurements. Ideally, spontaneous speech best reflects SFF; however, this task has not yet been clearly defined and is limited with regard to its adaptation to a clinical setting. A reliable task for SFF measurement in Japanese, which corresponds to a speech task that most closely reflects the value that would be observed with typical spontaneous speech, has not been investigated. This study aimed to identify a reliable speech task by measuring the SFF values elicited by different widely used speech tasks in Japanese, and assess its reliability and coefficient of determination (R2). METHODS: Sixty healthy volunteers (30 men and 30 women; aged 19-30 years; mean age 22.5 years) were enrolled. All experimental procedures were performed in Japanese. The SFF values for the speech tasks were determined through the voice samples recorded using a Pulse Code Modulation (PCM) recorder. Each task, except spontaneous speech, was repeated five times, and the average fundamental frequency in each task was determined as the SFF. To assess the reliability of the SFF values across daily variations within individual speakers, the SFF measurements were repeated on two different days, separated by at least 1 week. RESULTS: The SFF values of sustained /a/ phonation, sustained vowel-average, counting, reading passage, and spontaneous speech had excellent reliability, in terms of their reproduction based on intraclass correlation. Significantly high SFF values were observed, in decreasing order, for sustained vowels-average, counting, reading passage, and spontaneous speech in both males and females. The highest R2 for spontaneous speech was that of reading passage in both males (R2 = 0.771) and females (R2 = 0.806) (P < 0.01). CONCLUSION: When spontaneous speech was presented as a task most reflective of daily conversation, reading passage was determined to be the reliable task to assess the therapeutic effect of voice therapy in Japanese.

Age-dependent treatment effect of vocal fold steroid injection for benign vocal fold lesions.

Objective: Benign vocal fold lesions (BVFLs) cause voice disorders and impair social life. Recently, office-based vocal fold steroid injection (VFSI) has gained attention as a minimally invasive treatment for BVFLs. This study aimed to analyze the age-dependent treatment effect of VFSI and to clarify the indications for treatment. Methods: In this retrospective cohort study, a total of 83 patients with BVFLs were treated with a similar regimen of VFSI. Three or four months after the injection, age-dependent phonological functions were evaluated. The differences between pre- and post-treatment findings were analyzed using the Wilcoxon matched-pair signed-rank test, and the correlation between patient age and improvement rates were determined by Pearson's correlation coefficient. Results: Improvement in voice handicap index (VHI), which was the primary endpoint, was observed. Subjective and objective voice quality measurements also showed significant improvements. Subgroup analyses revealed that there was no age-related difference in the improvement of voice quality and that there was no improvement in aerodynamic effect in patients over 45 years of age. Conclusion: This study clarified the age-dependent treatment effect of VFSI and provided the important suggestion of establishing indication criteria for BVFLs. The study results provided clarity on the indication criteria of VFSI and served as an important indicator for tailoring treatment to patients' needs. Level of Evidence: 4.

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

BACKGROUND/AIM: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy. PATIENTS AND METHODS: A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference. RESULTS: The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072). CONCLUSION: There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.

Arytenoid adduction combined with medialization laryngoplasty under general anesthesia using a laryngeal mask airway.

PURPOSE: Laryngeal framework surgery is usually performed under local anesthesia but cannot be tolerated by some patients. To develop a new procedure for these patients, we evaluated voice outcomes after arytenoid adduction combined with medialization laryngoplasty under general anesthesia using a laryngeal mask airway (LMA) for unilateral vocal cord paralysis. MATERIALS AND METHODS: Eleven consecutive patients with severe unilateral vocal cord paralysis, with a maximum phonation time of less than 5 seconds, underwent arytenoid adduction combined with medialization laryngoplasty under general anesthesia using an LMA. Each paralyzed vocal cord was observed by intraoperative videolaryngoscopy. The vocal cord was moved to the position where the best vocal outcome could be expected, according to 3 parameters obtained from glottal images. RESULTS: All patients achieved a maximum phonation time of more than 11 seconds. The mean airflow rate, which ranged from 550 to 1000 mL/s before surgery, improved to less than 390 mL/s. Perceptual evaluation using the grade, roughness, breathiness, asthenia and strain scale also improved significantly. CONCLUSIONS: These results were equivalent to those of previous reports of surgeries performed under local anesthesia. Intraoperative endoscopic vocal cord observation through the LMA may have contributed to the positive results.

Effect of intracordal injection under local anesthesia on vital signs in high-risk patients.

OBJECTIVE: Intracordal injection under local anesthesia is widely performed; however, few studies show hemodynamic changes in the heart rate, blood oxygen saturation, and blood pressure during intracordal injection under local anesthesia. This study examined changes in vital signs (heart rate, blood oxygen saturation, systolic blood pressure, diastolic blood pressure) during intracordal injection under local anesthesia among high-risk patients and investigated whether intracordal injection under local anesthesia could be safely conducted. METHODS: A retrospective chart review was adopted as the research design. We investigated the changes in vital signs (heart rate, blood oxygen saturation, blood pressure) before and after intracordal injection with basic fibroblast growth factor (bFGF) preparations under local anesthesia in 46 patients who visited our institution and developed unilateral vocal cord paralysis after a thoracic aortic aneurysm, thoracic aortic dissection surgery, thyroid disease, esophageal disease, idiopathic disease, etc. RESULTS: The average operation time for the high-risk group was 3.67 minutes, with the shortest operating time being 2 minutes and the maximum operating time being 13 minutes. The average operation time for the control group was 3.73 minutes, with the shortest operating time being 1 minute and the maximum operating time being 9 minutes. Results before and after intracordal injection with bFGF preparations under local anesthesia for heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.324, 0.394, 0.215, and 0.508, respectively, in the high-risk group, and no significant differences were found. Conversely, heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.057, 0.232, 0.265, and 0.091, respectively, in the control group, and no significant differences were found. CONCLUSION: Intracordal injection under local anesthesia may be safe, even for patients who require blood pressure management after thoracic aortic disease surgery.

Long-term results and safety of fibroblast growth factor injection for unilateral vocal fold paralysis.

Objectives: Treatments for unilateral vocal fold paralysis (UVFP) include conservative voice rehabilitation, vocal fold injection, and laryngeal framework surgery. We proposed basic fibroblast growth factor (bFGF) injection as a potential novel treatment for UVFP and have reported the short-term results. In this study, we present the long-term results and safety of vocal fold bFGF injection as a treatment for UVFP. Methods: This retrospective study included 42 patients (25 males and 17 females) with UVFP who were administered a local injection of bFGF. The injection regimen involved injecting FGF (0.5 µg/ml in 0.5 ml per side) into the bilateral vocal folds using a 23-gauge injection needle. Phonological outcomes were evaluated 6 months and 12 months after the injection. Results: Overall, 26 patients received a single injection of bFGF, six patients received an additional injection, and 10 patients received the additional framework surgery. Maximum phonation time, mean flow rate, pitch range, jitter and shimmer percentages, the total GRBAS (grade, roughness, breathiness, asthenia, strain) score, and voice handicap index scores improved significantly in the long term. In patients who received the additional injection or framework surgery, the effects of bFGF injection were temporary, but did not interfere with the performance of the framework surgery. Conclusion: In total, 42 patients who underwent vocal fold bFGF injections were reviewed. The bFGF injections were effective and safe in the long-term results for UVFP in the selected cases. Some patients with severe symptoms benefited from the additional framework surgery but not the additional bFGF injection.

Intracordal injection therapy for vocal fold scarring: Steroid versus basic fibroblast growth factor.

Objectives: Vocal fold scarring is caused by replacement of vocal fold mucosa with fibrous tissue due to repeated inflammation or trauma. It can lead to severe dysphonia. It is currently treated conservatively and with phonosurgery and intracordal injections. Intracordal injection of steroid or basic fibroblast growth factor (bFGF) has been recently found to be useful for treating vocal fold scarring that does not respond to voice therapy. Methods: This retrospective study involved the administration of steroid injection and bFGF injection bilaterally under local anesthesia in 16 patients each. Laboratory measurements of voice parameters were performed before and 3-6 months after injection. Results: In the steroid injection group, the Voice Handicap Index (VHI) score significantly improved from 57.1 to 40.5, total Grade, Roughness, Breathiness, Asthenia, Strain (tGRBAS) score significantly improved from 4.2 to 2.6, and mean speech fundamental frequency (SFF) increased from 192.5 to 211.4 dB, but there was no improvement in maximum phonation time (MPT) and mean airflow rate (MFR). In the bFGF injection group, significant improvements in the VHI score (from 53.3 to 35.7), MPT (from 16.9 to 21.8 s) and MFR (from 314.6 to 210.5 ml/s) were seen; however, the tGRBAS score did not improve. In addition, the SFF significantly decreased from 178.1 to 160.5 Hz. Conclusion: These results suggest that both steroid and bFGF injections are effective for treating vocal fold scarring, with steroids improving voice quality and bFGF improving glottic closure, thereby contributing to improvements in VHI scores. Level of Evidence: 4.

Assessment of Dysphonia Using the Japanese Version of the Voice Handicap Index and Determination of Cutoff Points for Screening.

INTRODUCTION: The Voice Handicap Index (VHI) is recognized as a useful subjective assessment method for dysphonia. The original VHI has been translated into numerous other languages, including Japanese (J-VHI). Although the reliability and validity of the J-VHI have already been established, the cutoff point has not been determined. The aims of this study were to investigate the relationship between the J-VHI and other voice laboratory measurements, and determine the cutoff point. METHOD: This study included 167 dysphonic patients and 55 healthy volunteers. All patients and volunteers completed the J-VHI at the initial visit, and the following outcomes were determined: VHI scores of patients with dysphonia and healthy volunteers, VHI scores according to disease, cutoff point, and correlations between VHI scores and other voice laboratory measurements. RESULTS: Both the total VHI (VHI-T) and individual domain (functional domain [VHI-F], emotional domain [VHI-E], physical domain [VHI-P]) scores were significantly higher in the dysphonia group compared to the healthy volunteer group. VHI-T, VHI-F, and VHI-E scores were significantly lower in the benign mucosal lesion subgroup, compared to the other disease subgroups. The G scale and B scale of the grade-roughness-breathiness-asthenia-strain scale showed a significant association with VHI-T, VHI-F, and VHI-P scores. Similarly, the A scale showed a significant association with VHI-T, VHI-F, and VHI-E scores. The cutoff point (12) for VHI-T was chosen from the receiver operating characteristic curve to maximize sensitivity and specificity. Similarly, the cutoff points for VHI-F (5), VHI-P (5), and VHI-E (3) were also obtained. Significant differences in maximum phonation time, pitch range, G scale, and B scale were observed between the VHI-T negative (VHI ≤ 12) and positive (VHI-T > 13) groups. CONCLUSION: These findings suggest that self-evaluation using the VHI could serve as an independent assessment and screening tool for patients with dysphonia.

Predominant Vertical Location of Benign Vocal Fold Lesions by Sex and Music Genre: Implication for Pathogenesis.

OBJECTIVES/HYPOTHESIS: Vertical locations of vocal fold mucosal lesions (VFMLs) vary along the free edge. As the vertical contact area of vocal folds (VFs) depends on the vocal register, lesions may occur in the contact area of more frequently used vocal registers. This study investigated the cause of location variations by comparing the vertical sites of VFMLs in singers of both sexes with different music genres. STUDY DESIGN: Retrospective review. METHODS: Sixty professional classical and rock singers (11 male classical [M-classical], 22 male rock [M-rock], 13 female classical [F-classical], and 14 female rock [F-rock] singers) who underwent microlaryngeal surgery for VF polyps and nodules and their 108 lesions were enrolled. The VF free edge was vertically divided into three equal parts and classified into the following four lesion sites: upper, middle, lower, and multiple sites. RESULTS: Upper lesions were most common among F-classical singers (73.9%), whereas lower lesions were most common among M-classical (90.0%) and M-rock (60.6%) singers. Among lesions localized to a single site, lower lesions were most common among F-rock singers (37.0%). F-classical singers had significantly more upper lesions than the other groups (P < .001). M-classical singers had significantly more lower lesions than female singers of any genre (P < .001). CONCLUSION: Upper lesions were most common among F-classical singers who mostly used the head voice. Lower lesions were most common among singers who mainly used the modal voice. This study suggests that sex, the dominant vocal register used for singing, and mechanical stress on VFs influence the vertical site of VFMLs. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2284-E2291, 2021.

Validation of the Japanese Version of the Singing Voice Handicap Index.

PURPOSE: The aim of the present study was to translate the Singing Voice Handicap Index (SVHI) into Japanese and validate the Japanese version of the SVHI. METHODS: The SVHI was translated into Japanese from the validated original version, and the questionnaire was administered to 102 singers with voice problems and 88 healthy singers. Internal consistency and test-retest methods were implemented to evaluate the reliability of this index. The internal consistency method assessed validity via Cronbach's α, and test-retest reliability was analyzed by the intraclass correlation coefficient (ICC) and limits of agreement (LoA) according to the Bland Altman method. Construct validity was verified by confirming correlations between SVHI scores and visual analog scale (VAS) scores for disability in singing using Spearman correlation. Discriminant validity was evaluated by comparing SVHI scores between singers with voice problems and healthy singers using t tests. Using the Tukey's honestly significant difference (HSD) test, we also compared the Voice Handicap Index (VHI) and SVHI scores among three groups: healthy singers, singers with voice problems solely during singing, and singers with voice problems during both speaking and singing. RESULTS: The Japanese version of the SVHI showed excellent internal consistency (Cronbach's α = 0.981) and test-retest reliability (ICC: 0.93). The 95 percent LoA was calculated to be between -20.8 and 33.9. Construct validity was verified through correlated SVHI and VAS scores (r = 0.736, P < 0.001). Discriminant validity was verified as the SVHI scores of singers with voice problems were higher than those of healthy singers (77.8±37.5 vs. 30.0±26.5, P < 0.001). There were no statistically significant differences in VHI scores between singers with voice problems solely during singing and healthy singers; however, the SVHI scores of singers with voice problems solely during singing were significantly higher than those of healthy singers (63.4±36.8 vs. 30.0±26.5, P < 0.001). CONCLUSION: We confirmed that the Japanese version of the SVHI is a valid and reliable self-rated questionnaire for measuring the patient-perceived impact of singing voice problems among Japanese singers.

Comparison of therapeutic effects of steroid injection by benign vocal fold lesion type.

BACKGROUND: Benign vocal fold lesions (BVFLs) can cause voice changes, including reduced loudness and pitch range. In recent times, with progression in endoscopic technology, office-based vocal fold steroid injection (VFSI) has been used as an alternative therapy for BVFLs. AIMS/OBJECTIVES: In this study, we analyzed the efficacy and safety of VFSI to investigate the mechanism underlying its therapeutic effects and determine the conditions in which VFSI will be most effective. MATERIALS AND METHODS: In this retrospective cohort study, we included 40 condition-matched patients (8 patients per lesion) with chorditis, vocal nodules, vocal polyps, Reinke's edema (RE), or vocal scars who received similar regimens of steroid injection using a commercial preparation of triamcinolone acetonide. Their phonological outcomes were evaluated 2 or 3 months after the injection. RESULTS: Significant improvements were observed in Voice Handicap Index scores, results of laboratory voice evaluation, and voice quality measured using the Grade, Roughness, Breathiness, Asthenia, Strain scale in all participants. In subgroup analysis, VFSI was highly effective against chorditis and vocal nodules, but less effective against RE and vocal scars. CONCLUSIONS: Single-dose VFSI is valuable as an alternative to voice rehabilitation and laryngo-microsurgery, but higher concentrations or repeated injections are required for intractable lesions.