Sudden sensorineural hearing loss (SSNHL) is routinely encountered and is one of the most common emergent diseases in otolaryngology clinics. However, the etiology of SSNHL remains unclear. Due to the inaccessibility of the living human inner ear for biopsy, studies investigating the etiology of SSNHL have been performed by analyzing data obtained from examinations using peripheral blood or imaging. We updated the findings obtained from serological, magnetic resonance imaging, genetic, and viral examinations to reveal the etiology of SSNHL. Regarding viral examination, we focused on sensorineural hearing loss associated with coronavirus disease (COVID-19) because the number of correlated reports has been increasing after the outbreak. The updated findings revealed the following three possible mechanisms underlying the development of SSNHL: thrombosis and resulting vascular obstruction in the cochlea, asymptomatic viral infection and resulting damage to the cochlea, and cochlear inflammation and resulting damage to the cochlea. Thrombosis and viral infection are predominant, and cochlear inflammation can be secondarily induced through viral infection or even thrombosis. The findings about sensorineural hearing loss associated with COVID-19 supported the possibility that asymptomatic viral infection is one of the etiologies of SSNHL, and the virus can infect inner ear tissues and directly damage them.

Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is an independent tumour type with regard to cellular, biological, and clinical features. The use of non-invasive biomarkers such as circulating tumour DNA (ctDNA) may be relevant in early diagnosis and eventually improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC). Genome-wide discovery using RNA sequencing and reduced representation bisulfite sequencing yielded 21 candidates for methylation-targeted genes. A verification study (252 HNSCC patients) using quantitative methylation-specific PCR (Q-MSP) identified 10 genes (ATP2A1, CALML5, DNAJC5G, GNMT, GPT, LY6D, LYNX1, MAL, MGC16275, and MRGPRF) that showed a significant increase recurrence in methylation groups with OPC. Further study on ctDNA using Q-MSP in HPV-associated OPC showed that three genes (CALML5, DNAJC5G, and LY6D) had a high predictive ability as emerging biomarkers for a validation set, each capable of discriminating between the plasma of the patients from healthy individuals. Among the 42 ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 31 (73.8%), 19 (45.2%), and 19 (45.2%) samples, respectively. Among pre-treatment ctDNA samples, methylated CALML5, DNAJC5G, and LY6D were observed in 8/8 (100%), 7/8 (87.5%), and 7/8 (87.5%) samples, respectively. Methylated CALML5, DNAJC5G, and LY6D were found in 2/8 (25.0%), 0/8 (0%), and 1/8 (12.5%) of the final samples in the series, respectively. Here, we present the relationship between the methylation status of three specific genes and cancer recurrence for risk classification of HPV-associated OPC cases. In conclusion, ctDNA analysis has the potential to aid in determining patient prognosis and real-time surveillance for disease recurrences and serves as an alternative method of screening for HPV-associated OPC.

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common type of cancer, affecting ~500,000 individuals worldwide annually. Collagen is the major constituent of the extracellular matrix component in tumors and plays a crucial role in tumor development. The aim of this study was to determine the mRNA expression of type XXI, XXII, XXIII and XXIV α1 collagen (COL21A1, COL22A1, COL23A1 and COL24A1, respectively) in head and neck squamous cell carcinoma (HNSCC) and investigate its correlation with disease progression. This study investigated the mRNA expression levels of COL21A1, COL22A1, COL23A1 and COL24A1 in 70 HNSCC primary samples and 44 matched pairs of tumor and adjacent normal mucosal tissues using quantitative polymerase chain reaction (qPCR). Expression data were compared to the clinicopathological variables in order to determine the correlation between expression and disease progression. Our results demonstrated that the mRNA levels of COL22A1 and COL24A1 were significantly higher in HNSCC tissues compared to those in the corresponding normal tissues from the same individuals (n=44; P<0.001 and P=0.019, respectively). The COL22A1 mRNA levels were found to be significantly associated with lymph node metastasis (P=0.018) and pathological stage (P=0.024), whereas the COL24A1 mRNA levels were significantly associated with tumor size (P=0.045). The high expression levels of COL22A1 and COL24A1 mRNA were statistically correlated with a decrease in disease‑free survival (DFS) (log‑rank test, P<0.001). The results of the multivariate logistic regression analysis revealed that high expression levels of the COL22A1 and COL24A1 gene pair were associated with a high odds ratio for recurrence of 14.62 (95% confidence interval: 2.77‑77.26; P=0.002). Therefore, the upregulation of COL22A1 and COL24A1 mRNA may play a critical role in the progression of HNSCC and provide useful information as a prognostic predictor for HNSCC patients.

Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage 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. Cancer 2014;120:205–213. © 2013 American Cancer Society.

Association of TET3 epigenetic inactivation with head and neck cancer Association of TET3 epigenetic inactivation with head and neck cancer