Clinical Outcomes of Taiwanese Patients with Resected Oral Cavity Squamous Cell Carcinoma Who Underwent Reconstruction with Free Versus Local Flaps.

BACKGROUND: We sought to compare the clinical outcomes of Taiwanese patients with resected oral cavity squamous cell carcinoma (OCSCC) who underwent reconstruction with free versus local flaps. METHODS: From 2011 to 2017, we examined 8646 patients with first primary OCSCC who received surgery either with or without adjuvant therapy. Of these patients, 7297 and 1349 received free and local flap reconstruction, respectively. Two propensity score-matched groups of patients who underwent free versus local flap (n = 1268 each) reconstructions were examined. Margin status was not included as a propensity score-matched variable. RESULTS: Compared with local flaps, patients who received free flaps had a higher prevalence of the following variables: male sex, age < 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm, margin > 4 mm, extranodal extension (ENE), and adjuvant therapy (all p < 0.0001). Multivariable analysis identified the reconstruction method (local vs. free flaps, only overall survival [OS]), age ≥ 65 years, pT3-4, pN1-3, p-Stage III-IV, depth ≥ 10 mm (only OS), margins ≤ 4 mm, and ENE as independent adverse prognosticators for disease-specific survival (DSS) and OS. The results of propensity score-matched analyses revealed that, compared with free flaps, patients who underwent local flap reconstruction showed less favorable 5-year DSS (hazard ratio [HR] 1.26, 82%/77%; p = 0.0100) and OS (HR 1.21, 73%/68%; p = 0.0079). CONCLUSIONS: After adjusting for covariates using multivariate models, and also by propensity score modeling, OCSCC patients who underwent free flap reconstruction showed a higher frequency of clear margins and a significant survival advantage compared with those who received local flaps.

Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common.

BACKGROUND: The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan. METHODS: Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records. RESULTS: In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01). CONCLUSION: The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.

Band-Selection of a Portal LED-Induced Autofluorescence Multispectral Imager to Improve Oral Cancer Detection.

This aim of this study was to find effective spectral bands for the early detection of oral cancer. The spectral images in different bands were acquired using a self-made portable light-emitting diode (LED)-induced autofluorescence multispectral imager equipped with 365 and 405 nm excitation LEDs, emission filters with center wavelengths of 470, 505, 525, 532, 550, 595, 632, 635, and 695 nm, and a color image sensor. The spectral images of 218 healthy points in 62 healthy participants and 218 tumor points in 62 patients were collected in the ex vivo trials at China Medical University Hospital. These ex vivo trials were similar to in vivo because the spectral images of anatomical specimens were immediately acquired after the on-site tumor resection. The spectral images associated with red, blue, and green filters correlated with and without nine emission filters were quantized by four computing method, including summated intensity, the highest number of the intensity level, entropy, and fractional dimension. The combination of four computing methods, two excitation light sources with two intensities, and 30 spectral bands in three experiments formed 264 classifiers. The quantized data in each classifier was divided into two groups: one was the training group optimizing the threshold of the quantized data, and the other was validating group tested under this optimized threshold. The sensitivity, specificity, and accuracy of each classifier were derived from these tests. To identify the influential spectral bands based on the area under the region and the testing results, a single-layer network learning process was used. This was compared to conventional rules-based approaches to show its superior and faster performance. Consequently, four emission filters with the center wavelengths of 470, 505, 532, and 550 nm were selected by an AI-based method and verified using a rule-based approach. The sensitivities of six classifiers using these emission filters were more significant than 90%. The average sensitivity of these was about 96.15%, the average specificity was approximately 69.55%, and the average accuracy was about 82.85%.

ALPK1 Expression Is Associated with Lymph Node Metastasis and Tumor Growth in Oral Squamous Cell Carcinoma Patients.

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer, with high mortality rates in advanced stages. Recent studies have shown that the expression of ALPK1 mRNA and its inhibitory differentiation function are associated with cancer progression. However, the expression and clinicopathologic features of ALPK1 in OSCC remain unexplored. Herein, the authors investigated the expression patterns of ALPK1 in 39 matched OSCC patients and examined the relationship between ALPK1 protein expression and clinicopathologic factors using immunohistochemical scores. Using Western blot analysis, ALPK1 expression was found to be significantly higher in tumor tissues than that in nontumor tissues. Through an immunoreactive scoring system, a significantly higher number of advanced-stage tumor size T4 and lymph node metastasis N2 exhibited higher ALPK1 expression levels than that exhibited by T1/T2/T3 tumors and N0/N1. In addition, ALPK1 protein expression was aberrant in malignant oral cancer cell lines compared with that in pre-malignant oral epithelial cells, whereas minimal expression was observed in normal oral epithelial cells. Knockdown of ALPK1 resulted in a significant reduction in cell growth, migration, and invasion capacity in vitro. Consequently, expression of N-cadherin and vimentin decreased in ALPK1-deficient cells. Thus, these results suggest that ALPK1 serves as a potential biomarker and target for OSCC development in late stages.

The effect of metformin use on hypopharyngeal squamous cell carcinoma in diabetes mellitus patients.

BACKGROUND: Metformin is proven to improve the prognosis of various cancers, but it is unknown if metformin could ameliorate hypopharyngeal cancer in diabetes mellitus patients. This was a retrospective cohort study, and the effect and survival outcome of metformin on hypopharyngeal cancer with diabetes mellitus was investigated. METHODS: There were 141 hypopharyngeal cancer patients collected in a tertiary referral center from December 1st, 2011 to December 31st, 2013. There were 49 patients without diabetes mellitus (DM) and 92 patients with DM. In the 92 DM patients, there were 43 patients with metformin used and 49 patients without metformin used. All received patients followed up until September 1st, 2015. RESULTS: There was no significant difference in patients' characteristics between the non-DM and DM groups, and also no significant difference in clinical T stage, N stage, metastatic condition, and disease stage between the non-DM and DM groups. DM with metformin patients had lower metastasis rates and better overall survival (OS) (p = 0.011) and disease-free survival (DFS) (p = 0.004) compared to non-DM and DM without metformin. Multivariate analysis also showed a better OS and DFS in DM-Met (+) with advanced hypopharyngeal cancer but not in early stage. CONCLUSION: There was less distant metastasis and better survival outcomes in hypopharyngeal cancer DM patients who use metformin.

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Social and Cultural Context of Betel Quid Consumption in Taiwan and Implications for Prevention and Cessation Interventions.

BACKGROUND: In Taiwan, betel quid chewing is a part of social life for chewers. Betel quid itself, with or without tobacco, is a Group 1 human carcinogen. Betel quid chewing has become a severe health threat in Taiwan. OBJECTIVES: The aim of the present study was to identify the individual, social, contextual, and cultural factors related to initiation, continuous use, and cessation of betel quid chewing. METHODS: Four focus groups and 15 in depth face-to-face interviews were conducted in 2013 with current and former users of betel quid, members of a community organization located in central Taiwan. A thematic analysis identified themes evident across all groups. RESULTS: Study participants (N = 41) were 66% male and 34% female; mean age was 40.34 ± 9.23 years. Participants stated that betel quid initiation usually occurs during childhood and that the most frequent reasons for chewing were: to follow cultural/social traditions, to achieve an energetic feeling, and to avoid boredom. Participants perceived betel quid chewing as an addiction and a risk factor for cancer and other health-related conditions. The most frequently mentioned barriers to quitting betel quid included: peer pressure and selected withdrawal symptoms. CONCLUSIONS: For the development of culturally relevant and effective cessation interventions for betel quid in Taiwan, it is critical to understand and address perceptions of betel quid chewing and barriers to cessation.

AMPK-dependent signaling modulates the suppression of invasion and migration by fenofibrate in CAL 27 oral cancer cells through NF-κB pathway.

Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist and lipid-lowering agent, has been used worldwide for treatment of hyperlipidemia. The clinical trials demonstrate that fenofibrate possesses multiple pharmacological activities, including antitumor effects. However, the precise mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we investigated the anticancer effects of fenofibrate on the migration and invasion of human oral cancer CAL 27 cells. Fenofibrate inhibited the cell migration and invasion of CAL 27 cells by the wound healing and Boyden chamber transwell assays, respectively. In addition, fenofibrate reduced the protein expressions of MMP-1, MMP-2, MMP-7, and MMP-9 by Western blotting and inhibited enzyme activities of MMP-2/-9 using gelatin zymography assay. Results from immunoblotting analysis showed that the proteins of p-LKB1 (Ser428), LKB1, p-AMPKα (Thr172), p-AMPKα1/α2 (Ser425/Ser491), p-AMPKß1 (Ser108), and AMPKγ1 were upregulated by fenofibrate; the levels of p-IKKα/ß (Ser176) and p-IκBα were reduced in fenofibrate-treated cells. Also, fenofibrate suppressed the expressions of nuclear NF-κB p65 and p50 by immunoblotting and NF-κB DNA binding activity by EMSA assay. The anti-invasive effect of fenofibrate was attenuated by compound C [an adenosine 5'-monophosphate-activated protein kinase (AMPK) inhibitor] or dominant negative form of AMPK (DN-AMPKα1). Thus, fenofibrate considerably inhibited metastatic behaviors of CAL 27 cells might be mediated through blocking NF-κB signaling, resulting in the inhibition of MMPs; these effects were AMPK-dependent rather than PPARα signaling. Our findings provide a molecular rationale, whereby fenofibrate exerts anticancer effects and additional beneficial effects for the treatment of cancer patients. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 866-876, 2016.

Absorbable and nonabsorbable packing after functional endoscopic sinus surgery: systematic review and meta-analysis of outcomes.

The purpose of the study was to perform a systematic review and meta-analysis of the literature to compare the efficacy (and other postoperative outcomes) of nonabsorbable versus absorbable nasal packing after functional endoscopic sinus surgery (FESS) for the treatment of chronic rhinosinusitis. Studies were considered for inclusion if they were published in English language, were randomized clinical trials, and reported on outcomes following postoperative synechia. The primary outcome for meta-analysis was the incidence of postoperative synechia; pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using fixed-effects models. Five studies, involving 241 nasal cavities in each treatment group, were included in the systematic review. The prevalence of synechia ranged from 4.6 to 8.0 % in the absorbable groups and from 8.0 to 35.7 % in the nonabsorbable groups. Postoperative bleeding was lower in the absorbable groups, whereas there was no clear finding regarding postoperative pain. Postoperative edema was generally similar between groups. There were no consistent findings regarding bleeding and pain on packing removal. Two studies using the same type of packing material were included in the meta-analysis. The combined OR (0.33, 95 % CI 0.04-2.78) for postoperative synechia did not significantly favor (P = 0.308) absorbable packing over nonabsorbable packing. Although there is some evidence in the available literature that absorbable nasal packing may provide superior outcomes to nonabsorbable packing after FESS, the lack of homogeneity between studies makes definitive conclusions impossible. Further randomized clinical trials are needed to compare the efficacy of different types of absorbable nasal packing for preventing synechia after FESS.

Arecoline induces TNF-alpha production and Zonula Occludens-1 redistribution in mouse Sertoli TM4 cells.

BACKGROUND: Arecoline, a major alkaloid in Areca nut has the ability to induce oxidative stress. The effect of Areca nut, arecoline on reducing sperm quality and quantity were documented previously using several animal models. Junction disruption by down-regulation of the junction-adhesive protein via oxidative stress is an important route mediating abnormal spermatogenesis. Therefore, in this present study, we investigated the functional role of arecoline on junctional proteins. RESULTS: To analyze direct effects of arecoline on testis cells, confluent mouse testicular Sertoli cell line TM4 was exposed to arecoline. Arecoline decreased insoluble zonula occludens-1 (ZO-1) protein expression in TM4 cells, however, arecoline treatment increased TNF-alpha production in both TM4 and monocytic THP1 cells. In addition, ERK1/2 inhibitor PD98059 reversed arecoline effects on TNF-alpha and ZO-1. CONCLUSIONS: Arecoline increases the production of TNF-alpha and induces protein redistribution of ZO-1. All these results explain the role of arecoline in male reproductive dysfunction, besides its cytotoxic induction.

Decreased PLUNC expression in nasal polyps is associated with multibacterial colonization in chronic rhinosinusitis patients.

PLUNC (palate, lung, and nasal epithelium clone) is an epithelium-secreted protein that plays a crucial role in the host's defense against bacterial infection. The function of PLUNC in the sinus remains poorly understood. To examine whether the expression levels of PLUNC could serve as a predictive outcome biomarker for patients with CRSwNP and bacterial colonization, we investigated the association of PLUNC expression levels with bacterial colonization in the sinuses. A total of 174 patients who underwent sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled in this study. The tissue samples obtained from patients were examined using preoperative sinus computed tomography (CT) scans, postoperative bacterial cultures, and nasal polyp examinations. PLUNC mRNA and protein expression were quantified using RT-PCR and immunohistochemistry. We identified that decreased PLUNC expression is associated with multibacterial colonization (P = 0.0001), specifically those mediated by Staphyloccocus aureus (P = 0.037) and Pseudomonas aeruginosa (P = 0.002). The patients who required repeated sinus surgeries for recurrent or persistent sinusitis also presented much lower PLUNC expression than those who did not require repeated sinus surgery (P = 0.001). However, gender, age, and CT scores were not associated with PLUNC expression. These results suggest that reduced PLUNC expression is associated with bacterial colonization as well as treatment outcome in CRSwNP patients. Investigation of the association between PLUNC expressions and chronic rhinosinusitis may lead to the development of a novel biomarker for treatment outcome in CRSwNP patients.

A web-based audiometry database system.

To establish a real-time, web-based, customized audiometry database system, we worked in cooperation with the departments of medical records, information technology, and otorhinolaryngology at our hospital. This system includes an audiometry data entry system, retrieval and display system, patient information incorporation system, audiometry data transmission program, and audiometry data integration. Compared with commercial audiometry systems and traditional hand-drawn audiometry data, this web-based system saves time and money and is convenient for statistics research.

Syk/JNK/AP-1 signaling pathway mediates interleukin-6-promoted cell migration in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) typically migrates and metastasizes. Interleukin-6 (IL-6) is a multifunctional cytokine associated with disease status and cancer outcomes. The effect of IL-6 on human OSCC cells, however, is unknown. Here, we showed that IL-6 increased cell migration and Intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. Pretreatment of OSCC cells with IL-6R monoclonal antibody (mAb) significantly abolished IL-6-induced cell migration and ICAM-1 expression. By contrast, IL-6-mediated cell motility and ICAM-1 upregulation were attenuated by the Syk and c-Jun N-terminal kinase (JNK) inhibitors. Stimulation of OSCC cells with IL-6 promoted Syk and JNK phosphorylation. Furthermore, IL-6 enhanced AP-1 activity, and the IL-6R mAb, Syk inhibitor, or JNK inhibitor all reduced IL-6-mediated c-Jun phosphorylation, c-Jun binding to the ICAM-1 promoter, and c-Jun translocation into the nucleus. Our results indicate that IL-6 enhances the migration of OSCC cells by increasing ICAM-1 expression through the IL-6R receptor and the Syk, JNK, and AP-1 signal transduction pathways.

Cleaning and Harmonizing Medical Image Data for Reliable AI: Lessons Learned from Longitudinal Oral Cancer Natural History Study Data.

For deep learning-based machine learning, not only are large and sufficiently diverse data crucial but their good qualities are equally important. However, in real-world applications, it is very common that raw source data may contain incorrect, noisy, inconsistent, improperly formatted and sometimes missing elements, particularly, when the datasets are large and sourced from many sites. In this paper, we present our work towards preparing and making image data ready for the development of AI-driven approaches for studying various aspects of the natural history of oral cancer. Specifically, we focus on two aspects: 1) cleaning the image data; and 2) extracting the annotation information. Data cleaning includes removing duplicates, identifying missing data, correcting errors, standardizing data sets, and removing personal sensitive information, toward combining data sourced from different study sites. These steps are often collectively referred to as data harmonization. Annotation information extraction includes identifying crucial or valuable texts that are manually entered by clinical providers related to the image paths/names and standardizing of the texts of labels. Both are important for the successful deep learning algorithm development and data analyses. Specifically, we provide details on the data under consideration, describe the challenges and issues we observed that motivated our work, present specific approaches and methods that we used to clean and standardize the image data and extract labelling information. Further, we discuss the ways to increase efficiency of the process and the lessons learned. Research ideas on automating the process with ML-driven techniques are also presented and discussed. Our intent in reporting and discussing such work in detail is to help provide insights in automating or, minimally, increasing the efficiency of these critical yet often under-reported processes.

Endoscopic Versus Microscopic Type I Tympanoplasty: An Updated Systematic Review and Meta-analysis.

OBJECTIVE: Our objective was to perform a systematic review and meta-analysis comparing the clinical outcomes after endoscopic and microscopic type I tympanoplasty. STUDY DESIGN: Randomized controlled trials, two-arm prospective studies, and retrospective studies were included. SETTING: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until March 1, 2022 using the combinations of search terms: "endoscopic," "microscopic," and "tympanoplasty." METHODS: Two independent reviewers utilized the abovementioned search strategy to identify eligible studies. If any uncertainty existed regarding eligibility, a third reviewer was consulted. Primary outcome measures were graft success rate, air-bone gap (ABG) improvement, and operative time. Secondary outcomes were the rate of need for canalplasty, the proportion of self-rated excellent cosmetic results, and pain visual analog scale (VAS). RESULTS: Forty-three studies enrolled a total of 3712 patients who were undergoing type I tympanoplasty and were finally included. The pooled result showed endoscopic approach was significantly associated with shorter operative time (difference in means: -20.021, 95% confidence interval [CI]: -31.431 to -8.611), less need for canalplasty (odds ratio [OR]: 0.065, 95% CI: 0.026-0.164), more self-rated excellent cosmetic results (OR: 87.323, 95% CI: 26.750-285.063), and lower pain VAS (difference in means: -2.513, 95% CI: -4.737 to -0.228). No significant differences in graft success rate or ABG were observed between the two procedures. CONCLUSION: Endoscopic type I tympanoplasty provides a similar graft success rate, improvement in ABG, and reperforation rate to microscopic tympanoplasty with a shorter operative time, better self-rated cosmetic results, and less pain. Unless contraindicated, the endoscopic approach should be the procedure of choice in type I tympanoplasty.

Audiologic and vestibular assessment in patients with ß-thalassemia major receiving long-term transfusion therapy.

BACKGROUND: Life-long transfusion therapy with chelators is a treatment choice for patients with ß-thalassemia major. Some investigators have proposed auditory impairment related to the use of deferoxamine, but the mechanisms remain unclear and whether or not deferiprone has similar side effects needs to be evaluated. PROCEDURE: Thirty-seven patients with ß-thalassemia major who received regular transfusion in our hospital were enrolled. Chelation agents, including deferoxamine and deferiprone, were used. To assess audiologic function, otoscopy, pure tone audiometry (PTA), tympanometry, transient evoked oto-acoustic emission (TEOAE), and auditory brainstem response (ABR) were conducted. Bithermal caloric test was performed to evaluate vestibular function. RESULTS: All of the 37 patients had normal findings on otoscopic evaluation and their tympanograms were type A. Thirteen patients (35.1%) had hearing impairment at one or more frequencies as detected by PTA. Compared to those without hearing impairment, patients with hearing impairment had lower serum ferritin levels (P = 0.01). Seven of 21 patients (33.3%) failed to pass the TEOAE, while 13 (61.9%) had abnormal ABR findings. Sixteen patients (80%) had canal paresis in the caloric test. CONCLUSIONS: The incidence of auditory impairment and vestibular dysfunction was high in patients with ß-thalassemia major receiving long-term transfusion therapy. Potential lesions of auditory impairment may exist anywhere along the auditory pathway, from the inner ear to the brainstem. Lower serum ferritin levels may be associated with hearing impairment. Therefore, regular check-ups of serum ferritin levels and periodic audiologic assessment are mandatory.

CAR-T cells targeting HLA-G as potent therapeutic strategy for EGFR-mutated and overexpressed oral cancer.

Oral squamous cell carcinoma (OSCC) is a common malignancy in the world. Recently, scientists have focused on therapeutic strategies to determine the regulation of tumors and design molecules for specific targets. Some studies have demonstrated the clinical significance of human leukocyte antigen G (HLA-G) in malignancy and NLR family pyrin domain-containing 3 (NLRP3) inflammasome in promoting tumorigenesis in OSCC. This is the first study to investigate whether aberrant epidermal growth factor receptor (EGFR) induces HLA-G expression through NLRP3 inflammasome-mediated IL-1ß secretion in OSCC. Our results showed that the upregulation of NLRP3 inflammasome leads to abundant HLA-G in the cytoplasm and cell membrane of FaDu cells. In addition, we also generated anti-HLA-G chimeric antigen receptor (CAR)-T cells and provided evidence for their effects in EGFR-mutated and overexpressed oral cancer. Our results may be integrated with OSCC patient data to translate basic research into clinical significance and may lead to novel EGFR-aberrant OSCC treatment.

Longitudinal changes in swallowing function after surgery and proactive swallowing therapy for oral cancer.

BACKGROUND: This study aimed to describe and explore the longitudinal changes in swallowing function among patients with oral cancer who underwent surgery and proactive swallowing therapy from baseline to 1-year postoperation. METHODS: We retrospectively studied 118 patients over a 4.5-year duration. Swallowing functional assessment including 10-item Eating Assessment Tool (EAT-10), Functional Oral Intake Scale (FOIS), M. D. Anderson Dysphagia Inventory, and Modified Barium Swallow Impairment Profile (MBSImP™) was performed at baseline, 1-month, 6-month, and 1-year postoperatively. RESULTS: All swallowing parameters worsened 1-month postoperation. EAT-10, FOIS, and MBSImP™ oral and pharyngeal impairment scores improved significantly compared with 1-month postoperation at 6 months. Other swallowing parameters, except for weight, did not differ significantly from baseline at 6 months. The rate of tube-feeding dependency was 11.5% and 5.6% at 1 and 6 months postoperation, respectively. CONCLUSIONS: Periodic swallowing functional assessments help delineate the longitudinal changes in swallowing functional outcomes.

Performance and Operational Feasibility of Epstein-Barr Virus-Based Screening for Detection of Nasopharyngeal Carcinoma: Direct Comparison of Two Alternative Approaches.

PURPOSE: Two Epstein-Barr virus (EBV)-based testing approaches have shown promise for early detection of nasopharyngeal carcinoma (NPC). Neither has been independently validated nor their performance compared. We compared their diagnostic performance in an independent population. METHODS: We tested blood samples from 819 incident Taiwanese NPC cases (213 early-stage, American Joint Committee on Cancer version 7 stages I and II) diagnosed from 2010 to 2014 and from 1,768 controls from the same region, frequency matched to cases on age and sex. We compared an EBV antibody score using immunoglobulin A antibodies measured by enzyme-linked immunosorbent assay (EBV antibody score) and plasma EBV DNA load measured by real-time PCR followed by next-generation sequencing (NGS) among EBV DNA-positive individuals (EBV DNA algorithm). RESULTS: EBV antibodies and DNA load were measured for 2,522 (802 cases; 1,720 controls) and 2,542 (797 cases; 1,745 controls) individuals, respectively. Of the 898 individuals positive for plasma EBV DNA and therefore eligible for NGS, we selected 442 (49%) for NGS testing. The EBV antibody score had a sensitivity of 88.4% (95% CI, 86.1 to 90.6) and a specificity of 94.9% (95% CI, 93.8 to 96.0) for NPC. The EBV DNA algorithm yielded significantly higher sensitivity (93.2%; 95% CI, 91.3 to 94.9; P = 1.33 × 10-4) and specificity (98.1%; 95% CI, 97.3 to 98.8; P = 3.53 × 10-7). For early-stage NPC, the sensitivities were 87.1% (95% CI, 82.7 to 92.4) for the EBV antibody score and 87.0% (95% CI, 81.9 to 91.5) for the EBV DNA algorithm (P = .514). For regions with a NPC incidence of 20-100/100,000 person-years (eg, residents in southern China and Hong Kong), these two approaches yielded similar numbers needed to screen (EBV antibody score: 5,656-1,131; EBV DNA algorithm: 5,365-1,073); positive predictive values ranged from 0.4% to 1.7% and 1.0% to 4.7%, respectively. CONCLUSION: We demonstrated high sensitivity and specificity of EBV antibody and plasma EBV DNA for NPC detection, with slightly inferior performance of the EBV antibody score. Cost-effectiveness studies are needed to guide screening implementation.

Fenofibrate exhibits a high potential to suppress the formation of squamous cell carcinoma in an oral-specific 4-nitroquinoline 1-oxide/arecoline mouse model.

The excessive use of areca nut and/or tobacco may induce the production of free radicals and reactive oxygen species, which affect the lipid contents of the cell membrane and are possibly involved in tumorigenic processes in the oral cavity. The aim of this study was to investigate the therapeutic efficacy of fenofibrate (0.1% or 0.3%, w/w), a ligand of the peroxisome proliferator-activated receptor alpha (PPARα), in a 4-nitroquinoline 1-oxide (4-NQO)/arecoline-induced oral cancer mouse model. The carcinogen, 4-NQO/arecoline, was administrated to C57BL/6JNarl mice for 8weeks followed by fenofibrate treatment for 12 or 20weeks. After 28weeks, changes in serum lipids, the multiplicity of tumor lesions, and tumor sizes were determined together with changes in the immunohistochemical expressions of PPARα, acetyl-coenzyme A carboxylase (ACC), the epidermal growth factor receptor (EGFR), and cyclooxygenase-2 (COX2). The results showed that when compared to the 4-NQO/arecoline only group, 0.3% fenofibrate treatment increased serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. 0.3% fenofibrate treatment suppressed the incidence rate of tongue lesions, reduced the multiplicity of squamous cell carcinoma (SCC), decreased the tumor size, and increased the immunoreactivity of EGFR and COX2 in oral dysplasia but decreased EGFR and COX2 expressions in SCC. These findings indicated that fenofibrate reduced the tumor incidence rate and suppressed the tumor progression into SCC and that these molecular events might be linked to the EGFR and COX2 regulatory pathways. We suggest that fenofibrate provides a new strategy for preventing oral tumor progression.