Association of polymorphisms in Th1/Th2-related cytokines (IFN-γ, TGFß1, IL-1ß, IL-2, IL-4, IL-18) with oral lichen planus: A pooled analysis of case-control studies.

Background/purpose: Increasing evidence suggests that single-nucleotide polymorphisms (SNPs) in Th1/Th2-related cytokine genes correlated with oral lichen planus (OLP) susceptibility. However, these results were inconsistent and inconclusive. Hence, the aim of this study is to draw a more precise estimation of the genetic associations between SNPs in 6 cytokines (IFN-γ, IL-18, TGFß1, IL-1ß, IL-2, IL-4) and OLP. Materials and methods: A systematic literature search was conducted to identify all eligible case-control studies on the association between SNPs in 6 cytokines and OLP susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) from each study were pooled to estimate the strength of the association. Results: A significant association of IFN-γ (874A/T) polymorphism with OLP was found (OR, 1.49; 95%CI, 1.22-1.81; P < 0.001) based on 6 eligible studies. A significant association of IL-18 (137G/C) polymorphism with OLP was found (OR, 1.64; 95%CI, 1.24-2.18; P < 0.001) based on 3 studies. A marginally significant association of TGFß1 (509C/T) polymorphism in allele model with OLP was found (OR, 1.31; 95%CI, 1.01-1.71; P = 0.05) based on 4 studies. Nevertheless, lack of significant association of IL-1ß (3954C/T), IL-2 (330T/G), IL-4 (590C/T), and IL-18 (607C/A) polymorphisms with OLP was found (P > 0.05) based on 3 studies, respectively. Conclusion: This is the first meta-analysis to investigate the associations of 6 cytokines polymorphisms with OLP, suggesting that SNPs in IFN-γ, IL-18, and TGFß1 may act as genetic factors for OLP risk. Further well-designed studies with larger sample size and multiple ethnicities are needed to validate these associations.

Association of salivary miRNAs with onset and progression of oral potentially malignant disorders: Searching for noninvasive biomarkers.

Background/purpose: There is an urgent need for noninvasive biomarkers to diagnose oral potentially malignant disorders (OPMD). A wide range of over 20 miRNAs in saliva of OPMD patients have been investigated in different studies. Yet, which of the ones provide a better power of discrimination for the diagnosis of OPMD onset and progression are uncertain. Materials and methods: A total of 17 eligible studies including 426 cases of OPMD and 486 control subjects (352 normal mucosa and 134 oral squamous cell carcinoma) were summarized. Results: The bubble chart analysis showed that the most power salivary miRNA associated with OPMD onset was miR-21, followed by miR-31 and miR-142; the better power miRNAs associated with recurrence and malignant progression of OPMD were miR-31, miR-21, and miR-184. Conclusion: Salivary miRNAs, especially miR-21 and miR-31, were associated with onset and progression of OPMD, and could then serve as noninvasive biomarkers for screening OPMD and detecting malignant changes.

Salvianolic acid B as a potent nano-agent for enhanced ALA-PDT of oral cancer and leukoplakia cells.

BACKGROUND: Photodynamic therapy (PDT) relies on the light activation of a photosensitizers to generate reactive oxygen species such as singlet oxygen, but its effect on cancer therapy is limited dramatically by hypoxia in the tumor microenvironment. OBJECTIVES: To determine the potential of a nano-photosensitizer loaded salvianolic acid B (SalB) and 5-aminolevulinic acid (ALA) for enhancing the efficacy of PDT in oral squamous cell carcinoma Cal27 cells and leukoplakia Leuk1 cells. RESULTS: Singlet oxygen sensor green (SOSG) assay showed that nano-SalB-ALA generated higher levels of singlet oxygen, compared to nano-SalB and nano-ALA. Cellular uptake assay showed that nano-SalB-ALA effectively absorbed by Leuk1 cells. Importantly, cell counting kit-8 and flow cytometry revealed that PDT with nano-SalB-ALA effectively inhibited the viability and induced the apoptosis of Cal27 and Leuk1 cells, respectively. Moreover, the tumor xenograft study revealed that PDT with nano-SalB-ALA had a stronger inhibitory effect on tumor growth of nude mice, compared to control groups. CONCLUSIONS: The novel photosensitizer nano-SalB-ALA remarkably enhanced the efficacy of PDT by improving singlet oxygen production, inhibiting cell proliferation, promoting cell apoptosis, and suppressing tumor growth. These suggest PDT with nano-SalB-ALA could be a clinically significant and potent treatment for oral cancer and leukoplakia.

Chemopreventive efficacy of salvianolic acid B phospholipid complex loaded nanoparticles against experimental oral carcinogenesis: implication of sustained drug release.

Background: Although we have previously demonstrated that phospholipid complex loaded nanoparticles (PLC-NPs) encapsulating salvianolic acid B (SAB) can enhance anticancer activity in head and neck cancer and precancerous cells in vitro, the chemopreventive efficacy of SAB-PLC-NPs (nano-SAB) in vivo remains unclear. Here, we aimed to investigate the in vivo efficacy of nano-SAB against experimental oral carcinogenesis. Methods: Oral tongue carcinogenesis was induced in C57BL/6 mice through the administration of 4-nitroquinoline-N-oxide (4NQO, 100 µg/mL) in drinking water for 22 weeks. To preliminarily evaluate the effect of sustained drug release against oral carcinogenesis, free- or nano-SAB (16.6 mg/kg/d) was administered orally for 18 weeks, and the treatment was discontinued for the remaining 4 weeks. Results: Histological evaluation revealed a significant (P<0.05) decrease in the incidence of carcinoma in free-SAB-treated (16.7%) and nano-SAB-treated (10.0%) mice compared to mice exposed to 4NQO alone (34.3%). A decrease in carcinoma growth rate was also observed in free-SAB-treated (12.2%) and nano-SAB-treated (5.5%) mice compared to the 4NQO-exposed group (18.3%), even after drug withdrawal for 4 weeks. Immunohistochemical analysis revealed that nano-SAB treatment effectively suppressed Ki-67, proliferative cell nuclear antigen (PCNA), and cyclin D1 expression in high-risk dysplastic lesions compared to free-SAB-treated and 4NQO-exposed groups (all P<0.05). Importantly, nano-SAB maintained low levels of Ki-67, PCNA, and cyclin D1 expression even after drug withdrawal for 4 weeks. Conclusions: Together with our previous in vitro data, this in vivo study confirms that nano-SAB has superior chemopreventive efficacy by promoting more potent anti-proliferation and cell cycle arrest responses. These findings demonstrate the potential of SAB-PLC-NPs as promising chemopreventive agents for treating oral carcinogenesis.

LncRNA IFITM4P promotes immune escape by up-regulating PD-L1 via dual mechanism in oral carcinogenesis.

Oral squamous cell carcinoma (OSCC), which is typically preceded by oral leukoplakia (OL), is a common malignancy with poor prognosis. However, the signaling molecules governing this progression remain to be defined. Based on microarray analysis of genes expressed in OL and OSCC samples, we discovered that the long non-coding RNA IFITM4P was highly expressed in OSCC, and ectopic expression or knockdown of IFITM4P resulted in increased or decreased cell proliferation in vitro and in xenografted tumors, respectively. Mechanistically, in the cytoplasm IFITM4P acted as a scaffold to facilitate recruiting SASH1 to bind and phosphorylate TAK1 (Thr187), and in turn to increase the phosphorylation of nuclear factor κB (Ser536) and concomitant induction of PD-L1 expression, resulting in activation of an immunosuppressive program that allows OL cells to escape anti-cancer immunity in cytoplasm. In nucleus, IFITM4P reduced Pten transcription by enhancing the binding of KDM5A to the Pten promoter, thereby upregulating PD-L1 in OL cells. Moreover, mice bearing tumors with high IFITM4P expression had notable therapeutic sensitivity to PD-1 monoclonal antibody (mAb) treatment. Collectively, these data demonstrate that IFITM4P may serve as a new therapeutic target in blockage of oral carcinogenesis, and PD-1 mAb can be an effective reagent to treat OSCC.

Serum metabolite profiling of a 4-Nitroquinoline-1-oxide-induced experimental oral carcinogenesis model using gas chromatography-mass spectrometry.

BACKGROUND: Oral cancer progresses from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. The critical needs in oral cancer treatment are expanding our knowledge of malignant tumour progression and the development of useful approaches to prevent dysplastic lesions. This study was designed to gain insights into the underlying metabolic transformations that occur during the process of oral carcinogenesis. METHODS: We used gas chromatography-mass spectrometry (GC-MS) in conjunction with multivariate statistical techniques to observe alterations in serum metabolites in a 4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis model. Thirty-eight male rats were randomly divided into two groups, including the 4NQO-induced model group of 30 rats and the healthy control group of five rats. Animals were sacrificed at weeks 9, 13, 20, 24, and 32, post-4NQO treatment. Tissue samples were collected for histopathological examinations and blood samples were collected for metabolomic analysis. Partial least squares discriminate analysis (PLS-DA) models generated from GC-MS metabolic profile data showed robust discrimination from rats with oral premalignant and malignant lesions induced by 4NQO, and normal controls. RESULTS: The results found 16 metabolites associated with 4NQO-induced rat tongue carcinogenesis. Dysregulated arachidonic acid, fatty acid, and glycine metabolism, as well as disturbed tricarboxylic acid (TCA) cycle and mitochondrial respiratory chains were observed in the animal model. The PLS-DA models of metabolomic results demonstrated good separations between the 4NQO-induced model group and the normal control group. CONCLUSION: We found several metabolites modulated by 4NQO and provide a good reference for further study of early diagnosis in oral cancer.

Potential association between oral mucosal nevus and melanoma: A preliminary clinicopathologic study.

OBJECTIVES: To assess potential association between oral nevi (ON) and nevus-associated melanoma (NAM), in which melanoma cells coexist with nevus cells. METHODS: A total of 74 ON patients and 7 NAM patients were retrospectively reviewed. Comparative and regression analyses of clinical and histological data were performed between two groups. RESULTS: The mean age of the patients with ON was 36.5 years compared with that of 54.7 years of the patients with NAM (p = .008). Gender ratio was female predominance for ON (1.64:1 ratio) and male predominance for NAM (6:1 ratio). The most common location of ON and NAM was the palate (31.1%) and gingiva (71.4%), respectively. Univariate regression analysis revealed that elderly male patients (≥60 years) with junctional ON located on the gingiva correlate with higher risk of melanoma. Multivariate analysis revealed that junctional type of ON was an independent factor (adjusted OR, 38.32; 95% CI, 3.20-458.64; p = .004) associated significantly with increased risk for melanoma. CONCLUSIONS: The preliminary study for the first time elucidated the clinicopathologic features of a Chinese series of ON and evaluated the potential association between ON and NAM with a limited sample size. Further large multicenter studies are needed to confirm the findings.

Prevalence of and related risk factors in oral mucosa diseases among residents in the Baoshan District of Shanghai, China.

BACKGROUND: Oral mucosal diseases (OMDs) encompass a variety of different types of diseases. Our aim was to evaluate the prevalence and related risk factors of OMDs among residents in the Baoshan District of Shanghai, China, and provide a scientific basis for prevention and control strategies. METHODS: A sample of 653 residents aged 17 to 92 years from the Baoshan community was investigated in 2014. Each resident was surveyed by questionnaire to evaluate their oral mucosa and oral mucosa examinations were conducted. We followed up with 607 residents in 2018. All data were statistically analyzed using the SPSS 25.0 software package (Chicago, IL, USA) at the general population, gender and age levels. A X2 test was used to compare rates of risk factors and logistic regression analysis was used to detect the correlation between disease and risk factors. RESULTS: The prevalence rate of OMDs was found to be 9.19%-9.56% (2014-2018). The most common OMDs were atrophic glossitis (1.84%), recurrent aphthous ulcer (RAU, 1.68%), burning mouth syndrome (BMS, 1.38%), oral lichen planus (OLP, 1.23%) and traumatic ulcers (1.23%). The prevalence of RAU and BMS in different age groups was significantly different. Tobacco and alcohol use and psychological factors in the OMDs group were higher than the no-OMDs group. Systemic diseases including diabetes mellitus (DM) was significantly relevant to OLP. CONCLUSION: Age, tobacco and alcohol use, and psychological factor correlated strongly with the occurrence and development of OMDs, and they should be the focus of primary prevention. General epidemiological studies suggested that OLP was closely related to DM.

Podoplanin and ABCG2 expression in oral erythroplakia revisited: Potential evidence for cancer stem cells driving the process of field cancerization.

A model of field cancerization orchestrated by the cancer stem cells (CSC) was proposed. Podoplanin and ABCG2 are promising marker of CSCs for head and neck cancer. We revisited the correlation of the two markers with the follow-up data of the patients with oral erythroplakia (OE). Strikingly, we observed that the expression of podoplanin and ABCG2 within a single pre-neoplastic OE lesion significantly correlate with subsequently developing multiple and multifocal carcinomas, thus to some extent demonstrating the concept of field cancerization. Collectively, a point to highlight was that a preliminary evidence that provided by this revisited study supported the perspective on cancer stem cells driving the process of field cancerization.

Cancer stem cell markers ALDH1 and Bmi1 expression in oral erythroplakia revisited: Implication for driving the process of field cancerization.

The correlation of ALDH1 and Bmi1 expression in potentially malignant oral erythroplakia (OE) with oral carcinoma development was reported in our earlier study. Interestingly, a model of field cancerization orchestrated by the cancer stem cells (CSC) was proposed and suggested the identification of CSC-specific markers is useful for prognosis and providing novel targets for prevention and treatment of field cancerization. We revisited the correlation of ALDH1 and Bmi1 expression in OE with the second and multiple carcinomas development. Strikingly, we observed that the expression of ALDH1 and Bmi1 within a single potentially malignant OE lesion significantly correlate with subsequently developing multiple and multifocal carcinomas, which parallels the process of oral field cancerization. Significantly, ALDH1 and Bmi1 are well-defined markers of CSC for head and neck cancer. Consequently, we provided a preliminary evidence for CSC driving the process of field cancerization.

Clinical effect of auricular point therapy on burning mouth syndrome / 口腔疾病防治

Objective@#To evaluate the clinical efficacy of auricular acupoint application in the treatment of burning mouth syndrome(BMS).@*Methods@#A total of 155 patients diagnosed with BMS were randomly divided into the auricular acupoint application group (50 patients), drug treatment group (55 patients), and auricular acupoint application combined with drug treatment group (50 patients). One month represented one course of treatment. The changes in pain intensity were evaluated before treatment as well as one month and three months after treatment.@* Results@#The VAS scores in the auricular acupoint application group (t=8.949), the drug treatment group (t=10.52) and the auricular acupoint application combined with drug treatment group (t=19.33) all decreased 1 month after treatment, with a statistically significant difference compared with the scores before treatment (P < 0.01). The VAS scores of the auricular acupoint application combined with drug treatment group decreased significantly, and the difference was statistically significant compared with the scores in the drug treatment group (t=3.91, P=0.000 2). 3 months after treatment, the VAS scores of the three group decreased compared with that before treatment, but increased compared with that 1 month after treatment, and the VAS score of the drug treatment group increased most obviously, but the difference was not statistically significant compared with that of the auricular acupoint application group (t=2.047, P=0.043), other pairwise comparison differences were not statistically significant. There was no statistically significant difference in VAS score in the auricular acupoint application group (t=1.752) and in the drug treatment group (t=0.174) compared with that before treatment (P > 0.05). Compared with before treatment, the VAS score in the auricular acupoint application combined with drug treatment group also decreased significantly (t=3.282, P < 0.05). @*Conclusion@#Auricular point application is a safe and effective treatment for burning mouth syndrome, and the long-term effect is better when combined with drugs.

Differential expression of ghrelin and GHSR via the mTOR pathway during the dynamic carcinogenic process involving oral, potentially malignant disorders.

The purpose was to explore the sequence changes in ghrelin and GHSR in the mTOR signaling pathway during carcinogenesis involving oral, potentially malignant disorders (OPMD). The samples were confirmed through in vivo pathologic tissue screening and diagnosis. The immunohistochemical method was used to detect the expression of the ghrelin/growth hormone secretagogue receptor (GHSR) protein. The expression of ghrelin, GHSR 1α, GHSR 1ß, and mammalian target of rapamycin (mTOR) RNA were detected by real-time PCR. The expression of ghrelin, GHSR, mTOR, and phosphorylated mTOR (phosphor-mTOR) protein were detected by Western blot. The expression of ghrelin/GHSR increased gradually in the dynamic process of OPMD carcinogenesis. There was a correlation between the increase in ghrelin, GHSR, mTOR, and phospho-mTOR. The in vivo expression of ghrelin/GHSR protein was the most apparent pathologic change from normal-to-mild, moderate, and severe dysplasia, and finally to the dynamic process from normal-to-mild-to-moderate dysplasia. The in vitro cell experiments based on QPCR results also proved that GHSR 1a functional receptor of ghrelin had a peak expression in LEUK-1 cells. In conclusioin, the close relationship between ghrelin and OPMD carcinogenesis can be used as a new biological target to assess the carcinogenesis of OPMD.

Risk Factors Associated With Malignant Transformation in Patients With Oral Leukoplakia in a Chinese Population: A Retrospective Study.

PURPOSE: The study aim was to investigate the risk factors for the progression of oral leukoplakia (OLK) to malignancy. PATIENTS AND METHODS: The data from 2,628 patients with OLK were retrospectively reviewed. Of these 2,628 patients, 192 had undergone sequential biopsies and were separated into 4 groups according to their final diagnosis. The risk factors were analyzed using Kaplan-Meier univariate survival analysis and Cox multivariate analysis. RESULTS: In 41 of the 2,628 patients (1.7%), the OLK had progressed to cancer, with a mean interval to malignancy of 26.7 months. Of the 192 patients with sequential biopsies, OLK was maintained or had progressed to mild, moderate, or severe dysplasia or carcinoma in 50, 66, 35, and 41 patients, respectively. The 3- and 5-year oral cancer-free survival (OCFS) was 78.9 and 72.5%, respectively. The factors associated with worse overall survival were lesions located in the ventral tongue (P = .04), alcohol use (P = .025), nonhomogeneous lesions (P < .01), and high-risk dysplasia (P < .01). Cox regression analyses indicated that nonhomogeneous lesions (P = .03) and high-risk dysplasia (P < .01) were independent prognostic factors for the progression of OLK to malignancy. CONCLUSIONS: High-risk dysplasia and nonhomogeneous lesions were shown to be important factors for progression to malignancy in patients with OLK. Thus, such patients should receive close follow-up and undergo sequential biopsies in the first 2 to 3 years for early screening of OLK evolving into a malignancy.

Potential role of autofluorescence imaging in determining biopsy of oral potentially malignant disorders: A large prospective diagnostic study.

Autofluorescence examination of oral tissues using the VELscope has been suggested as an adjunctive tool for cancer detection and diagnosis. This study aimed to determine the diagnostic value of VELscope in a large prospective study of 517 patients with oral potentially malignant disorders (OPMD). For the outcome assessments of discrimination of carcinoma form general OPMD and distinguishing high-risk lesions (moderate/severe dysplasia and carcinoma) from low-risk lesions (no/mild dysplasia), high sensitivity (100% and 95.9% respectively) and negative predictive value (100% and 98.2% respectively) were observed. All the carcinoma and showed loss of autofluorescence (LAF) and only 3 (0.6%) moderate/severe dysplasia were observed without LAF. These data indicate that the cases without LAF using VELscope substantially rule out the presence of high-risk lesions including cancer. This may prove to be useful specially to alleviate patient anxiety regarding a clinically suspicious oral lesion without the LAF, and to avoid a unnecessary biopsy for these cases. Collectively, a perspective to highlight was that a no biopsy strategy may be appropriate for OPMD without LAF using VELscope after conventional oral examination.

Role of the human papillomavirus in malignant transformation of oral leukoplakia distinct from oropharyngeal squamous cell carcinoma: A study of 76 patients with internal-control specimens.

OBJECTIVE: This study sought to investigate the role of human papillomavirus (HPV) in the carcinogenesis of oral leukoplakia (OLK), with the oral cavity as the site of interest. STUDY DESIGN: A total of 76 patients (152 specimens) were enrolled in the study. The patients were divided into 2 groups: the malignant transformation of OLK (OLK-MT) group and the non-malignant transformation of OLK (OLK-non-MT) group. HPV reverse dot blot analysis, HPV DNA polymerase chain reaction (PCR), and p16INK4A immunohistochemistry (IHC) were used to determine HPV infection status. RESULTS: Transformation of OLK commonly occurred in the lateral/ventral tongue, buccal mucosa, and gingiva. On the basis of the initial analysis of specimens, only 5.3% (4 of 76) of patients were found to be HPV-16 positive, and these patients' final specimens yielded negative results. Overexpression of p16INK4A in the dysplastic stage was associated with the transformation of OLK (P = .013; odds ratio = 3.544). CONCLUSIONS: Transformation of OLK was common in patients who are elderly, in females, and in nonsmokers/nondrinkers; lesions were located in the lateral/ventral tongue, with dysplasia and overexpressed p16INK4A seen during the initial stage. HPV may be an opportunistic infection in the oral cavity and may not be a cause of malignant transformation of OLK. p16INK4A expression, which initially increases and then diminishes or disappears, may be an early predictor of malignant transformation.

A Cross-Sectional Study of Oral Lichen Planus Associated With Thyroid Diseases in East China.

Objective: To investigate the prevalence of thyroid diseases in patients with oral lichen planus (OLP) and to explore the correlation between the two diseases. Methods: A cross-sectional study was conducted to investigate the history of thyroid disease in 585 patients with oral lichen planus diagnosed in the Department of Oral Mucosal Diseases of the Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine from June 2017 to April 2018 and in 10,441 normal people in an epidemiological survey conducted by endocrinology department of Ninth People's Hospitalin eastern China from 2014 to 2015. Personal medical history of thyroid disease was obtained through questionnaire and thyroid function was also tested. Results: Of the 585 patients with OLP, 190 (32.48%) had thyroid disease (excluding coexistence of multiple thyroid diseases), 62 (32.6%) had thyroid nodules, and 71 (37.4%) had Hashimoto's thyroiditis. Hyperthyroidism was diagnosed in six patients (3.2%), hypothyroidism in seven patients (3.7%), and thyroid cancer in 11 patients (5.8%). The prevalence of Hashimoto's thyroiditis was significantly higher in patients with oral lichen planus than in the general population. The probability of thyroid disease was significantly higher in women with OLP than in men with OLP (P < 0.001). Conclusion: OLP is associated with a high probability of developing thyroid disease, especially Hashimoto's thyroiditis. In the management of OLP patients, especially in female patients, thyroid disease must be screened.

Human papillomavirus genotypes and p16 expression in oral leukoplakia and squamous cell carcinoma.

Several studies have shown a broad variation in the prevalence of human papillomavirus (HPV) in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), whereas the relationship is less well-defined and specific HPV genotypes lack examination in OLK. In the present study, the role of HPV and surrogate p16 expression was investigated to explore the correlation and pathogenesis in OLK and OSCC. Polymerase chain reaction (PCR) and flow-through hybridization technology were utilized to detect HPV genotypes in oral exfoliated cells from 30 healthy volunteers, 103 OLK and 30 OSCC patients. Expression of p16 was assessed by immunohistochemistry (IHC) in biopsies from these OLK and OSCC, in addition to 15 normal oral mucosal tissues as the control group. The healthy controls showed 3.3% (1/30) HPV presence; In OLK and OSCC, the detection rate was 4.9% (5/103), 3.3% (1/30), respectively. No significant relationship between HPV and OLK or OSCC was observed when compared with the control group (P>0.05). All 6 HPV-positive OLK and OSCC cases had p16 overexpression. But the sensitivity of p16 IHC was poor, because 88.4% (38/43) of p16 over-expressed OLK were HPV negative. There was no statistical significance between HPV and the sex, age, site, alcohol consumption, or smoking. These findings suggested HPV had a low prevalence in OLK and OSCC. This suggests the detection of HPV genotypes by PCR in exfoliated cells combined with p16 IHC may be more accurate to represent HPV infection.

A prognostic scoring model based on the HPV status of oropharyngeal carcinoma patients treated with postoperative radiotherapy in China.

OBJECTIVES: Prognostic models that can predict prognosis and guide postoperative radiotherapy (PRT) and that are based on the human papillomavirus (HPV) status of patients with oropharyngeal carcinoma (OPSCC) in China are rare. METHODS: Survival was analyzed by performing a Kaplan-Meier analysis and log-rank test. A Cox regression analysis was performed for the multivariate analyses. A prognostic scoring model was constructed according to the regression coefficient obtained from the Cox regression model. RESULTS: A prognostic model that included gender, clinical stage, histologic stage, metastasis, and HPV status was created and used to divide patients into high-risk (PI ≥ -0.008) and low-risk (PI < -0.008) groups. The results showed that the patients who received PRT had a longer overall survival time than those who did not receive PRT (47.31 months vs. 28.31 months). Furthermore, the patients who received PRT in the high-risk group had a longer survival time when the survival was greater than 20 months (P = 0.024), and PRT may indicate a worse prognosis in the low-risk group (P = 0.071). CONCLUSION: This model will contribute to the formulation of individualized treatment programs for OPSCC patients. PRT should be administered to high-risk patients.

Expression of DNA doublestrand repair proteins in oral leukoplakia and the risk of malignant transformation.

The present study assessed the expression of the DNA doublestrand repair (DDR) proteins ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2) and γH2A histone family member X (γH2AFX) in oral leukoplakia (OL) and evaluated their clinical significance and usefulness as biomarkers for predicting OL transformation. Retrospectively, ATM, CHEK2 and γH2AFX protein levels were evaluated using immunohistochemical analysis in 61 OL, 33 oral squamous cell carcinoma (OSCC) and 15 normal oral mucosa tissues. OL tissues were classified into two groups according to the epithelial dysplasia pathology: The low risk dysplasia group (n=41) and the high-risk dysplasia group (n=20). The results of the present study revealed that the expression of ATM and γH2AFX in OSCC was significantly increased compared with that in OL with low-risk dysplasia and normal oral mucosa tissues. There was no statistically significant difference in CHEK2 expression among the groups. ATM expression was correlated with that of γH2AFX in OSCC tissue. The prognostic values of the DDR proteins and their correlation with clinical and pathological parameters were evaluated further in 99 OL patients with low risk dysplasia. Multivariate analysis revealed that increased expression of ATM and γH2AFX was significantly associated with an increased risk of malignant transformation. Immunohistochemical analysis of ATM and γH2AFX protein expression provided useful prognostic information on the carcinogenesis of OL. Increased ATM and γH2AFX expression may indicate a poor prognosis.