Search

Oral cancer, a subtype of head and neck cancer, is characterized by increased infiltrating regulatory T cells (Treg); however, the pathological significance of the increase in Tregs in disease prognosis and progression and their underlying mechanism remain unestablished. C‐C motif chemokine ligand 22 (CCL22) has been implicated in the recruitment of Tregs. We used RT‐qPCR to determine CCL22 mRNA expression in clinical specimens and cultured cells. Loss‐of‐function and gain‐of‐function studies were carried out to analyze the effects of CCL22 modulations on cell proliferation, migration, invasion, and tumorigenesis and the mechanism involved in the deregulation of CCL22. In oral cancer specimens, CCL22 mRNA was upregulated. The increase was not only associated with reduced disease‐free survival but also strongly correlated with an increase in FOXP3 mRNA, a master regulator of Treg development and functions. Silencing CCL22 expression reduced cell proliferation, migration, and invasion, whereas ectopic overexpression showed opposite effects. Manipulation of CCL22 expression in cancer cells altered tumorigenesis in both immune‐compromised and ‐competent mice, supporting both autonomous and non‐autonomous actions of CCL22. Release of interleukin 1β (IL‐1β) from cancer‐associated fibroblasts (CAF) induces CCL22 mRNA expression in oral cancer cells by activating transcription factor nuclear factor kappa B (NF‐κB). Our data support a model in which CAF‐derived IL‐1β, CCL22, and its receptor CCR4 foster a protumor environment by promoting cell transformation and Treg infiltration. Intervention of the IL‐1β‐CCL22‐CCR4 signaling axis may offer a novel therapeutic strategy for oral cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract: Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population‐based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra‐nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause‐specific survival (CSS), local‐regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P < .001). Extreme RT dose (>70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery. [ABSTRACT FROM AUTHOR]

Summary: Early-stage oral cancer patients may have distinct clinical outcomes and respond differently to the same treatment. Up to now, there is still no individual marker to identify such patients with poor outcome. Down-regulation of a tumor suppressor gene, S100A2, in oral cancer cells was identified by mRNA profiling analysis then confirmed by RT-PCR and Southern blotting. The expression of nuclear S100A2 protein examined by immunohistochemistry was not significantly associated with any patient characteristic among the 70 early-stage oral squamous cell carcinoma (SCC) patients. Intriguingly, the loss of nuclear S100A2 positivity was significantly associated with shorter disease-free survival (p =0.019) while having no effect on the overall survival of these patients. Cox regression analysis with backward elimination identified S100A2 (p =0.006), tobacco smoking (p =0.013), and betel quid chewing (p =0.019) as independent predictors of disease-free survival. This is a first study to demonstrate that loss of nuclear S100A2 may serve as an independent prognostic marker for early-stage oral cancer patients at high risk of recurrence. A more aggressive treatment modality and intensive follow-up may be recommended for the patients with reduced expression of S100A2 in tumor cell nuclei. [Copyright &y& Elsevier]

Oral cancer is one of the most common types of human cancer in the world. Although the risk factors for oral cancer are well-recognized in different countries, the molecular mechanism responsible for this malignancy remains elusive particularly in the countries where betel quid chewing is prevalent. The cDNA microarray analysis was used to analyse the mRNA expression patterns of 1177 genes in ten oral cancer patients with betel quid chewing history. Eighty-four genes involving cell adhesion, cell shape, growth, apoptosis, angiogenesis, metastasis, and metabolism were deregulated. Although the expression profile of these genes was shared by certain clinical patients, there was no significant association of the expression profile with clinical staging. Functional implication of four validated genes including caspase-1, STAT-1, COX-2 and pleiotrophin was discussed. This study provides pilot data for understanding the pathogenesis of oral cancer in countries like Taiwan where betel quid chewing is prevalent. [Copyright &y& Elsevier]

Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle which can be detected immunohistochemically in paraffin-embedded tissue as a useful marker for the proliferating fraction of cells in tissue specimens. Thirty-eight cases of oral squamous cell carcinoma were studied in groups according to clinical staging and histological grading (UICC system), these included 5 cases of T1, 13 cases of T2, and 20 cases of T3, and 19 cases of Gl, 12 cases of G2, and 7 cases of G3. The mean percentage of PCNA positively stained tumor cells in this series was 29.2. The mean percentages of PCNA-positive cells in each stage and grade were: T1 (13.7%), T2 (24.4%), and T3 (34.3%); GI (30.5%), G2 (24.8%), and G3 (33.2%). The results indicate that the percentage of PCNA positively stained tumor cells in oral squamous cell carcinoma was significantly greater when tumor size was larger than 2 cm (T1 versus T2/T3). However, there was no significant difference between T2 and T3. There was no correlation between the number of PCNA- stained tumor cells and histological grade. [ABSTRACT FROM AUTHOR]

The choice of salvage modalities of recurrent squamous cell carcinoma (SCC) of the oral cavity remains controversial. We investigated the feasibility of the surgical salvage treatment as a primary option. From 1989 to 1999, curative intended surgery was performed on 191 patients with SCC of the oral cavity at National Cheng Kung University Hospital in Taiwan. These patients were divided into fresh group and salvage group. Survival and complication rates were analyzed for both groups. Patients with early and late recurrent stage had 60 and 38% 5-year absolute survival after salvage surgery. The overall complication rate was higher in the salvage group (60.7 vs 30.4%, P<0.0001), but the major complication rate was not significantly different between these groups (P=0.121). Surgery achieves an acceptable survival in recurrent oral SCC without increasing the major complication rate. Thus surgery is concluded to be a reliable and feasible treatment of choice. [Copyright &y& Elsevier]

Objectives: We assess the incremental cost-effectiveness ratio (ICER) of the oral cancer (OC) screening program in Taiwan.Materials and Methods: We interlinked the Cancer Registry, Mortality Registry, National Vital Statistics, reimbursement database of National Health Insurance, and the National Oral Cancer Screening database of Taiwan. A total of 40,092 pathologically verified OC patients were identified and followed during 2002-2014. After stratification by stages, lifetime survival curves were estimated by a rolling extrapolation algorithm to obtain life expectancy (LE), expected years of life lost (EYLL), and lifetime medical costs (LMC).Results: The LE for stages I-IV were 19.5, 14.0, 11.9, and 7.7 life-years, respectively, while those of EYLL were 7.3, 12.2, 15.4, and 18.7 life-years, respectively. The LMC for stages I-IV were US$ 65,752, 60,086, 53,675, and 47,570, respectively. We assumed no life loss for stage 0 with LMC of US$ 5380 spent for the first year after diagnosis. During 2010-2013, 967 out of the 28,018 cases detected with abnormal oral pathology by screening were found to develop OC. The ICER of the screening program was US$ 28,516 per life-year saved, which could be improved to US$ 5579 per life-year saved if all cancers transformed from abnormal oral pathology were detected before stage I.Conclusion: The ICER of the current OC screening program in Taiwan slightly exceeds 1 GDP (gross domestic product) per capita per life-year saved. Intensive follow-up and treatment for all patients with abnormal oral pathology would improve screening efficiency and effectiveness of prevention. [ABSTRACT FROM AUTHOR]

Summary Objectives This analysis examined the life expectancies (LE) and expected years of life lost (EYLL) in relation to oral cancer in Taiwan. Materials and methods A semi-parametric extrapolation method was applied to estimate gender, age, histology, subsite, and stage stratified LE, EYLL of 22,024 pathologically verified oral cancer patients retrospectively recruited from the National Cancer Registry of Taiwan during 2002–2009, who were followed up to 2011. Results The patients were predominantly male 20,101, (91.3%), and over 80% were less than 65 years old. The mean age at diagnosis of males was younger than that of females (52.73 years vs. 60.76 years). The LE after diagnosis was longer among females than males (15.26 years vs. 12.73 years), with a smaller loss of the corresponding EYLL (8.88 years vs. 14.05 years), which prevails after stratification by age and stage. More than half of the oral cancer cases were diagnosed at a later stage, with 2921 cases (13.3%) of stage III and 8488 (38.5%) of stage IV. The five-year overall survival rate of oral cancer for stages I, II, III, and IV were 78.98%, 69.38%, 54.62%, and 36.17%, respectively. The earlier the diagnosis, the longer the life expectancy and the smaller the EYLL. Conclusions We concluded that early detection and early intervention of oral cancer can prolong life expectancy and reduce the years of life lost, indicating the importance of proactive screening and oral hygiene. [ABSTRACT FROM AUTHOR]

Little is known about the specificity of angiogenic properties of oral cancer cells and the possible mechanisms. Stimulatory effects on proliferation and migration of human umbilical vein endothelial cells (HUVEC) characterized the angiogenic properties of oral cancer cells but not normal oral keratinocytes (NOK). ELISA found the presence of vascular endothelial growth factors (VEGF) both in the tested oral cancer cells and NOK. Attenuation of the proangiogenic effects by neutralizing VEGF antibodies suggests VEGF play a key role in the acquisition of the angiogenic phenotype in oral cancer cells. Western blotting of p53 and murine double mutant 2 (Mdm2) together with p53 DNA sequencing analysis indicate that p53 function loss by mutation or overexpression of Mdm2 occurred in all tested oral cancer cells regardless of their etiology. In summary, the angiogenic property of oral cancer cells is mediated by many factors in addition to VEGF and the functional status of p53. [ABSTRACT FROM AUTHOR]

Background: Margin status and lymph node metastasis are the most important prognostic factors for oral cancers. However, while adequate surgical resection is crucial for local control and prognosis, the definition of clear margins has long been a subject of debate. In this study, we analyzed data from a nationwide population-based cancer registry database and evaluated the impact of surgical margins on cancer-specific survival (CSS) and overall survival (OS) as well as the optimal cutoff of adequate surgical margins.Methods: This analysis included all cases of oral cancer diagnosed from 2011 to 2017 that were reported to the Taiwan Cancer Registry database. The staging system was converted from American Joint Committee on Cancer (AJCC) version 7 to AJCC version 8. Kaplan-Meier analysis and Cox proportional-hazards regression were performed to identify covariates that were significantly associated with CSS and OS.Results: Between 2011 and 2017, 15,654 of a total of 36,091 cases diagnosed with oral cancers were included in the final analyses. Advanced N stage, positive margins, and advanced T stage are the leading risk factors for poor CSS and OS. When surgical margins were subdivided into 1-mm intervals from 5 mm to positive margin, we found that surgical margins <4 mm and <5 mm predict poor CSS and OS, respectively.Conclusions: This is the first nationwide, population-based cohort to revisit the question of the adequate surgical margins for oral cancers. We conclude that surgical margins ≥4 mm and ≥5 mm are adequate for good CSS and OS, respectively. [ABSTRACT FROM AUTHOR]