Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend ...of HPV‐related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV‐related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV‐related and HPV‐unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV‐related and HPV‐unrelated HNC in Taiwan both rose during 1995–2009. The incidence of HPV‐related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p < 0.0001) rose more rapidly than the incidence of HPV‐unrelated HNC (10.4 per 100,000 in 1995 to 21.7 in 2009, APC = 5.0, p < 0.0001). The rising trend of HPV‐related HNC was particularly prominent for HNC occurring in tonsil (APC = 8.2, p < 0.0001), in men (APC = 7.5, p < 0.0001), and in those aged between 40 and 50 years (APC = 8.5, p < 0.0001). Although the overall incidence of HNC in Taiwan has continued to increase, the most rapid rise is in the HPV‐related HNC. This suggests that similar to the Western world, HPV‐related HNC is becoming an important public health issue in Taiwan.
What's new?
Taiwan is home to one of the highest incidence rates of head and neck cancer (HNC) in the world, primarily because of betel quid chewing. In the Western world, by contrast, overall HNC incidence is decreasing, while human papillomavirus (HPV)‐related HNC is accounting for a greater proportion of cases. This analysis indicates that HPV‐related HNC is on the rise in Taiwan as well. Between 1995 and 2009, the country's incidence rates for HPV‐related HNC rose more rapidly than HPV‐unrelated HNC. The findings suggest that HPV is a global issue in HNC.
Objectives/Hypothesis
Transoral robotic surgery (TORS) in the base of the tongue (BOT) reduction has been shown to decrease the apnea‐hypopnea index (AHI) and improve daytime sleepiness in ...obstructive sleep apnea (OSA) patients. Intraoperative ultrasound (IOU) can be employed to guide the surgery and prevent massive bleeding.
Study Design
Cohort study with historical control.
Methods
A cohort study to compare the outcomes between OSA patients who received TORS with and without IOU assistance.
Results
From 2016 to 2019, this study enrolled 80 OSA patients who underwent TORS in BOT: 57 in the IOU(+) and 23 in IOU(−) groups. The TORS with IOU presented with shorter operative time, less blood loss, and greater excised BOT volume. The IOU(+) group had greater improvement in the AHI and subjective questionnaire evaluation. The excised volume of BOT was significantly associated with the change in AHI.
Conclusion
The IOU could improve outcomes in BOT reduction surgery without raising the risk of surgical complications.
Level of Evidence
4 Laryngoscope, 132:1125–1131, 2022
Epigenetic silencing of retinoic acid (RA) signaling-related genes have been linked with the pathogenesis and clinical outcome in oral squamous cell carcinoma (OSCC) carcinogenesis. However, the ...precise mechanisms underlying the abnormal silencing of RA signaling-related genes in OSCC have not been well investigated.
Using combined analysis of genome-wide gene expression and methylation profile from 40 matched normal-tumor pairs of OSCC specimens, we found a set of retinoid signaling related genes are frequently hypermethylated and downregulated in OSCC patient samples, including alcohol dehydrogenase, iron containing 1 (ADHFE1) and aldehyde dehydrogenase 1 family, member A2 (ALDH1A2), which are the important rate-limiting enzymes in synthesis of RA. The expression of ADHFE1 and ALDH1A2 in OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. The binding sites of miR-30a and miR-379 with DNA methyltransferase 3B (DNMT3B) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and Western blot analyses. The functions of miR-30a, miR-379, and DNMT3B were accessed by growth and colony formation analyses using gain- and loss-of-function approaches. Chromatin immunoprecipitation (ChIP) was performed to explore the molecular mechanisms by arecoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) treatment.
We demonstrated that deregulated miR-30a and miR-379 could represent a mechanism for the silencing of ADHFE1 and ALDH1A2 in OSCC through targeting DNMT3B. Ectopic expression of miR-30a and miR-379 could induce re-expression of methylation-silenced ADHFE1 and ALDH1A2, and lead to growth inhibition in oral cancer cells. Furthermore, the dysregulation of the miRNAs and DNMT-3B may result from exposure to tobacco smoking and betel quid chewing.
Our results demonstrate that tobacco smoking and betel quid chewing could repress miR-30a and miR-379, which upregulate the DNMT3B expression, in turn, lead to the hypermethylation of ADHFE1 and ALDH1A genes, consequently, promote the oncogenic activity. These findings highlight the potential use of retinoids in combination with epigenetic modifiers for the prevention or treatment of oral cancer.
The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in ...2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.
•Down-regulation of CISH in OSCC tissues and cell lines.•CISH mediates cellular functions through STAT3 inhibition.•MiR-944 regulates cellular functions through direct binding of CISH.•Cigarette ...smoking-mediated miR-944/CISH/STAT3 axis plays a role in oral carcinogenesis.
The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.
microRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 ...pairs of betel quid-associated oral squamous cell carcinoma (OSCC) specimens and their matched nontumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared with the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated as Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR329 and miR410, which could potentially target Wnt-7b, an activator of the Wnt-β-catenin pathway, thereby attenuating the Wnt-β-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR329 or miR410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to reexpress miR329, miR410, and Meg3, consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR329, miR410, and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contributes to oral carcinogenesis through epigenetic silencing of tumor-suppressor miRNA that targets Wnt-β-catenin signaling.
Objectives/Hypothesis
To investigate the lingual artery (LA) position in the tongue base through intraoperative ultrasound (IOU) imaging during transoral robotic surgery (TORS) and evaluate bleeding ...complications with or without the assistance of IOU.
Study Design
Cohort study with historical control.
Methods
Patients with obstructive sleep apnea (OSA) who underwent TORS for tongue base resection were recruited since 2016. During surgery, ultrasound imaging was employed to identify anatomic parameters of the LA in the tongue base, including distance to the midline and arterial depth and diameter.
Results
Ninety‐three OSA patients (82 men, 88.2%) were analyzed. Mean age was 42.2 ± 10.0 years and body mass index was 29.2 ± 4.5 kg/m2. Average apnea–hypopnea index (AHI) was 58.1 ± 21.4 events/hour. Overall, 70 patients who underwent TORS with IOU had a shorter operation time (191.7 ± 3.8 vs. 220.1 ± 6.6 minutes), lower total blood loss (11.3 ± 10.8 vs. 19.6 ± 26.7 mL), and higher tongue base reduction volume (7.1 ± 2.5 vs. 3.9 ± 1.6 mL) than 23 patients who underwent TORS without IOU. Significant predictors of arterial depth included higher AHI level during the rapid eye movement sleep (P = .038), larger tonsil size (P = .034), and more elevated Friedman tongue position (P = .012). Postoperative complications associated with LA injury were not found in patients subjected to IOU.
Conclusions
With the assistance of IOU, surgeons can confidently determine LA position. The use of IOU can maximize efficiency and minimize catastrophic bleeding complications when OSA patients undergo TORS for tongue base resection.
Level of Evidence
4 Laryngoscope, 131:E1383–E1390, 2021
This study showed an interaction between oral bacteria, lifestyle factors and genetic polymorphisms on the risk of oral cancer. The results also provided biological support for the established ...association between poor oral hygiene and oral cancer risk.
Abstract
Poor oral hygiene may lead to overgrowth of pathogenic oral bacteria, which may induce chronic inflammation to promote the oncogenesis of oral squamous cell carcinoma (OSCC). This study investigated the association between oral bacterial profile and OSCC risk in a case-control study of 138 OSCC cases and 151 controls (88 cases and 90 controls for the discovery group and 50 cases and 61 controls for the validation group). Oral bacterial profiles were characterized by targeted sequencing of the 16S rRNA gene. Three species of periodontopathogenic bacteria, Prevotella tannerae, Fusobacterium nucleatum, and Prevotella intermedia, were associated with an increased OSCC risk. This association was modified by the genetic polymorphisms of TLR2 and TLR4. Use of alcohol, betel quids and cigarettes and poor oral hygiene were associated with a higher percentage of oral periodontopathogenic bacteria. The association between alcohol and periodontopathogenic bacteria was modified by the genetic polymorphism of ALDH2, with a stronger positive association observed among the ALDH2-deficient individuals. The percentage of periodontopathogenic bacteria was positively correlated with the level of salivary IL1β, an inflammatory cytokine. Overall, our results showed a positive association between periodontopathogenic bacteria and OSCC risk and this relationship may be influenced by lifestyle and genetic factors. Our results provided further biological support for the established association between poor oral hygiene and OSCC risk. This suggested that improving oral hygiene may reduce OSCC risk and should be part of a public health campaign to prevent the occurrence of OSCC.
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