Prognostic importance of DNA from human papillomavirus in patients with oral squamous cell carcinoma

Background Survival of patients with oral squamous cell carcinoma (OSCC) is generally low, with the likelihood of locoregional recurrence or disease progression (LR/DP). Knowledge of prognostic factors for survival is key to achieving an understanding and increased survival. The present study aimed to identify prognostic factors for patients with OSCC, especially the presence of DNA from human papillomavirus (HPV).Material and Methods Retrospective cohort study including 119 patients with OSCC treated at the National Cancer Institute in Mexico City (2009-2013). Clinical information was obtained from patient records including LR/DP. Formalin-fixed, paraffin-embedded tissues were obtained and used for detecting DNA from different types of HPV. Potential prognostic factors for Overall Survival (OS) were analyzed using the Cox proportional hazards model.Results After model adjustment, factors associated with longer OS were a pre-treatment platelet count above 400,000/mm3 (HR=0.09, p=0.026) and response to primary treatment (HR=0.26, p=0.001). HPV DNA was present in 23 (19.3%) of the patients and importantly, type 16 found in 19 of them. Although survival of HPV-positive patients was longer, difference was not significant. However, among patients with LR/DP, HPV positivity was significantly associated with increased survival (HR=0.23, p=0.034). Importantly, survival was significantly different for HPV-positive patients with LR/DP > 6 months (HR=0.20, p=0.002), had higher absolute lymphocyte count at start of treatment (HR=0.50, p=0.028) or had local rescue treatment (HR=0.24, p=0.019).Conclusions Although HPV positivity was not associated with a longer OS of OSCC patients, a better prognosis was significantly associated with HPV positivity and recurring or progressing disease, particularly with HPV type 16. Key words:HPV, human papillomavirus, HPV-16, oral squamous cell carcinoma, oral cancer, survival, locoregional recurrence, disease progression.     

PD-L1的表达与口腔鳞癌预后及临床病理特征相关性的meta分析

目的: 采用meta分析评价PD-L1的表达与口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）预后及临床病理特征的关系。方法: 检索PubMed、EMBASE以及Cochrane等数据库中关于PD-L1蛋白表达与OSCC预后和临床病理特征相关的实验研究,采用RevMan 5.3软件进行meta分析。结果: 最终纳入12个研究共1595例患者。Meta分析合并风险比（HR）为1.02（95%CI= 0.93-1.11,P=0.71）,表明PD-L1的表达与OSCC生存率无显著相关性。合并比值比（OR）显示,PD-L1与患者性别（OR=0.64,95%CI=0.48-0.85,P=0.002）、肿瘤分化程度 （OR=0.58,95%CI=0.37-0.90,P=0.01）以及是否合并HPV感染（OR=1.91,95%CI=1.13-3.23,P=0.02）密切相关,但与肿瘤大小、颈淋巴结转移无明显相关性。结论: PD-L1的表达并不能作为判断OSCC预后的独立因素。在临床病理特征方面,PD-L1的表达与患者性别、肿瘤分化程度、HPV感染有显著相关性。该结论尚待更大样本的研究予以验证。     

中性粒细胞/淋巴细胞比值与口腔鳞状细胞癌预后相关性的Meta分析

目的探讨中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)患者预后及其临床病理特征的相关性。方法检索PubMed、Web of Science、Cochrane以及Embase等数据库中关于NLR与OSCC预后及临床病理特征相关性的文献,纳入结局的指标包括总体生存率(overall survival,OS)、无病生存率(disease free survival,DFS)、疾病特异性生存期(disease specific survival,DSS)、肿瘤大小、颈淋巴结转移、肿瘤分期、淋巴结包膜外侵犯、周围神经侵犯,采用RevMan5.3软件进行分析。结果纳入23篇文献,共计6 180例患者。分析显示NLR与OS[HR=1.62,95%CI(1.38,1.91),P <0.001]、DFS[HR=1.48,95%CI(1.24,1.77),P <0.001]、DSS[HR=1.87,95%CI(1.60,2.20),P <0.001]呈负...     

IFNAR1在口腔鳞状细胞癌中的表达及意义

目的：观察Ⅰ型干扰素受体1（type I interferon receptor 1,IFNAR1）在口腔鳞状细胞癌（oral squamous cell carcinoma,OSCC）及正常口腔黏膜中的表达,探讨其与患者临床特征及预后的关系。方法：应用免疫组织化学方法检测IFNAR1在108例OSCC及16例正常黏膜组织中的表达水平,分析IFNAR1的表达水平与OSCC临床病理特征的关系。采用SPSS17.0软件包对数据进行统计学分析。结果：IFNAR1在OSCC的表达水平比正常黏膜组织高。IFNAR1的表达水平与T分期、颈淋巴结转移、TNM分期及病理分化程度显著相关（P<0.05）;与患者的性别、年龄、发生部位、吸烟和饮酒无相关性（P>0.05）。IFNAR1表达对OSCC患者生存预后的HR=1.879 （95%CI=0.967-3.651,P=0.063）。Log-rank检验显示,IFNAR1表达高低与OSCC患者预后相关（P=0.057）。结论：IFNAR1在OSCC患者中高表达,其表达上调对OSCC是一个潜在的危险因子,与OSCC患者的预后有相关趋势。     

Does the geriatric nutrition risk index predict the prognosis of patients with oral squamous cell carcinoma?

Malnutrition is associated with the prognosis of malignant disease. The geriatric nutritional risk index (GNRI), based on serum albumin (ALB) levels and the present and ideal body weight, is a simple screening tool with which to predict the risk of malnutrition and mortality in patients. We hypothesised that nutritional markers could predict the prognosis of patients with oral squamous cell carcinoma (OSCC). The primary predictor variable was the GNRI score and the primary outcome variable was overall survival (OS). Univariate and multivariate analyses were performed using a Cox proportional hazard model to identify independent prognostic factors. The sample comprised 155 patients, of whom 17 presented with a low GNRI score (≤98) and 138 with a high GNRI score (≥ 98). There was a significant difference in OS when patients were stratified according to GNRI scores, with OS rates of 29.2% and 76.4% for scores of 98 and under and scores of over 98, respectively (p < 0.001). Univariate analyses showed that OS was significantly associated with GNRI score, age, T classification, N classification, stage, body mass index (BMI), prognostic nutrition index, and ALB levels. Analysis identified three independent predictive factors for OS: age (hazard ratio (HR) 2.184; 95% confidence interval (CI) 1.119 to 4.261; p = 0.022), stage (HR 2.684; 95% CI 1.457 to 5.367; p = 0.011), and GNRI score (HR 4.559; 95% CI 2.172 to 9.570; p <0.001). The results suggest that the GNRI score (>98 vs ≤98) is a good prognostic marker in patients with OSCC, along with age and stage.     

Prognostic significance of dysplasia associated with oral squamous cell carcinoma in patients undergoing surgery with curative intent

The aim of this study was to evaluate the prognostic significance of dysplasia in patients undergoing primary surgery with curative intent in the treatment of oral squamous cell carcinoma (OSCC). This study specifically aimed to demonstrate the effect of dysplasia on local recurrence, disease specific survival (DSS) and overall survival (OS). Data collection for 833 patients with OSCC undergoing treatment for curative intent was undertaken retrospectively for the period of February 2006 to May 2020. Analysis of any association between known clinicopathological prognostic categorical variables with respect to dysplasia was undertaken using the chi squared test. A Kaplan-Meier analysis was performed to demonstrate the impact of dysplasia on DSS and OS, and Cox’s proportional-hazards model deployed to obtain hazard ratios associated with dysplasia and the outcomes of interest. Dysplasia was statistically significant in predicting disease specific and overall survival in patients undergoing primary surgery for OSCC (DSS p<0.001, HR 0.577; 95%CI 0.428 to 0.777), OS p<0.001 HR 0.691; 95%CI 0.562 to 0.850) with the absence of dysplasia predicting poorer outcomes. The absence of dysplasia correlated with pathological higher T and N stage, increased categorised depth of tumour invasion, non-cohesive invasive front, lymphovascular invasion, perineural invasion, extranodal extension and increased modified Glasgow Prognostic Score. No significant prognostic relationship was attributable to the presence of dysplasia at a surgical margin. The absence of dysplasia appeared to be a significant independent prognostic indicator for patients with OSCC. The presence or absence of dysplasia may provide a heuristic means of stratifying OSCC primary lesions in terms of disease hostility.     

Is the addition of extranodal extension and lymph node yield of pN0 to the lymph node ratio useful as a prognostic parameter for patients with oral squamous cell carcinoma?

We investigated the value of the weighted lymph node ratio (WLNR), a new marker in pN0 patients that incorporates the number of metastatic lymph nodes with extranodal extension and the lymph node yield, for the prognosis and postsurgical management of oral squamous cell carcinoma (OSCC). We designed a retrospective study and enrolled patients with OSCC who were treated by neck dissection (ND). The predictor variable was WLNR, and the outcome variable was overall survival (OS). The Cox proportional-hazards model was used to identify independent prognostic factors. In 133 patients with OSCC, the WLNR cut-off value for predicting OS was 0.0363 (area under the curve 0.723, p<0.001). When stratified according to WLNR, there was a significant difference in OS (88.4% for low WLNR and 63.0% for high WLNR, p<0.001). Univariate analyses showed close associations between OS and age, dissection area, postoperative management, extranodal extension, number of positive lymph nodes, pN stage, WLNR, and nodal disease area. Cox multivariate analysis identified the WLNR as an independent predictive factor for OS (HR 3.273, 95% CI 1.227 to 8.731, p=0.018). As a predictive factor, a high WLNR (≥0.0363) in patients with pN0 disease, which included the addition of extranodal extension and lymph node yield to the LNR, was associated with diminished survival.     

Postoperative adjuvant therapy for patients with loco-regionally advanced oral squamous cell carcinoma who are at high risk of recurrence

Extranodal extension (ENE) of lymph node metastasis and the presence of a positive or close margin (PCM) are major risk factors for head and neck squamous cell carcinoma recurrence. This retrospective multicentre cohort study compared the prognostic impact of postoperative radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in oral squamous cell carcinoma (OSCC) patients at high risk of recurrence. One hundred and eighteen patients with PCM and/or ENE who underwent definitive surgery plus either adjuvant RT or CCRT using cisplatin for OSCC were investigated. The cohort-wide 5-year loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates (the main outcome measures) were 54.3%, 35.8%, and 43.2%, respectively. Multivariate analysis showed that age ≥64 years (hazard ratio (HR) 0.584), cT3–4 stage (HR 1.927), ≥4 metastatic lymph nodes (HR 1.912), and PCM (HR 2.014) were significant independent predictors of OS. Moreover, postoperative CCRT with cisplatin was associated with a significantly improved LRC rate, but not with improved DFS or OS rates, compared to postoperative RT (HR 0.360). Given that CCRT with cisplatin does not significantly improve survival, additional clinical trials will be required to validate new regimens that further improve the outcomes of patients with loco-regionally advanced OSCC going forward.     

经首次根治性手术治疗口腔鳞状细胞癌患者的生存相关影响因素分析

目的分析口腔鳞状细胞癌(OSCC)患者的总体生存率,以及影响生存率的临床病理因素。方法采集对首次接受根治性外科手术治疗的78例OSCC患者的临床病理及随访资料进行回顾性分析。对计数、计量资料进行描述性分析;采用Kaplan-Meier法绘制生存曲线;采用COX比例风险回归模型进行单因素和多因素分析,分析患者的生存率及预后相关影响因素。结果最终纳入生存分析的患者共计68例,中位随访时间为63(6~87)个月,5年总体存活率为55.9%,随访期间因OSCC死亡患者的中位生存时间为20.5(6~52)个月。单因素分析表明,临床分期、原发灶大小、淋巴结转移、病理分化及复发转移是影响生存时间的暴露因素(P<0.05);多因素分析表明,病理分化、复发转移是影响生存时间的独立危险因素(P<0.05)。78例OSCC患者中合并发生食道鳞状细胞癌(ESCC)者有4例(5.1%)。结论根据肿瘤的临床分期(TNM分期)、原发灶大小、淋巴结转移、病理分化及复发转移可对患者的生存预后作出一定的预测,其中病理分化及复发转移是影响生存预后的独立危险因素。有吸烟饮酒史的OSCC患者应常规进行ESCC临床筛查。     

Evaluation of sarcopenia and sarcopenic obesity in patients affected by oral squamous cell carcinoma: A retrospective single-center study

This retrospective single-center study aimed to evaluate the relevance of sarcopenia and sarcopenic obesity as negative prognostic factors in patients with oral squamous cell carcinoma (OSCC).The study was performed on patients who underwent oral squamous cell carcinoma resection surgery. Patients’ demographic and clinical variables were collected at diagnosis (sex, age, height, weight, comorbidities, smoke and alcohol consumption, HPV positivity, TNM-stage) and corrected for known prognostic factors (age, body mass index, TNM-stage). The Skeletal Muscle Mass (SMM) and the Cross-Sectional Area (CSA) on pre-treatment CT scans and Body Mass Index (BMI) were measured to assess sarcopenia and sarcopenic obesity correlated to overall survival (OS).Chi-square statistics were used to analyze the differences between the frequencies of each categorical variable with the presence or absence of sarcopenia and sarcopenic obesity. The cumulative overall survival was calculated by the Kaplan-Meier method, and the differences between curves were evaluated by the log-rank test. A Cox proportional hazard regression model was used for univariate and multivariate analysis of the overall survival.Within the limitations of the study, in this sample, sarcopenia did not seem to cause a statistically significant reduction in the overall survival in patients with oral squamous cell carcinoma (Log Rank χ2 = 3.67, p = 0.055; HR 0.996, 95% CI 0.732–1.354, p = 0.979), however, sarcopenic obesity showed a meaningful negative prognostic impact on it (Log Rank χ2 = 5.71, p = 0.017; HR 0.985, 95% CI 0.424–2.286, p = 0.972).Within the limitations of the study it seems that sarcopenic obesity, age, BMI, and TNM-stage are more relevant negative prognostic factors, influencing overall survival in surgically treated OSCC, than sarcopenia.     

Carcinoma squamoso orale: caso clinico di una paziente non sottoposta a terapia con follow-up di 32 mesi

ObjectivesCases of patients affected by oral squamous cell carcinoma (OSCC) and not treated with surgery or radio-chemotherapy have not been reported yet. We present a case of an untreated patient with a 32-month follow-up.Materials and methodsA 95-year-old woman presented with a squamous cell carcinoma of the buccal and palatal gingiva from 1.3 to 2.2. Because of the patient's age, we decided not to treat the lesion with surgery or radio-chemotherapy.ResultsCurrently, the patient has a 32-month follow-up, without any evident worsening of her health.ConclusionsOSCC surgical therapy and radiotherapy often cause terrible deficiencies with a significant worsening in patients’ quality of life. Even if it has not been reported a cut-off age for surgical treatment, the need of therapy should be decided according to the patient's age, other diseases and quality of life.     

口腔鳞癌腮腺淋巴结转移的临床病理特征与预后分析

目的:探讨口腔鳞癌患者腮腺淋巴结转移的临床病理特征及预后影响因素.方法:回顾性分析2003年1月—2017年12月上海交通大学医学院附属第九人民医院收治的60例伴或不伴腮腺淋巴结转移的口腔鳞癌患者的临床病理资料及影像学资料,分析其临床病理和影像学特征及其与预后的相关性.采用SPSS 23.0软件包对数据进行统计学分析....     

Retropharyngeal lymph node metastasis in oral cancer. Systematic review and survival analysis

IntroductionMetastasis to retropharyngeal lymph nodes (RPLN) from oral squamous cell carcinoma is rare and associated with poor outcomes. The poor prognosis of RPLN is multifactorial and includes the clinicopathological aggressiveness of the primary disease and the late presentation. The aim of this systematic review is to assess the evidence on RPLN in patients diagnosed with oral squamous cell carcinoma (OSCC), the quality of the diagnostic modalities and the available treatment options. We aimed to analyse the overall survival of these patients diagnosed with RPLN.MethodsA systematic review was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The initial literature search generated 289 articles. A total of 11 papers satisfied our criteria. Eight papers provided enough data to perform survival analysis and 3 papers compared the diagnostic modalities used in the detection of RPLN.ResultsA total of 73 OSCC patients diagnosed with RPLN metastasis were identified. The most common primary tumour subsites included the tongue (20), buccal mucosa (15) and gingiva (11). The cumulative 5-year OS rate was 17.8% while the 2-year overall survival was 35.9%.ConclusionThe presence of nodal metastasis is an independent prognostic factor in head and neck cancer. In this study, RPLN metastasis had a poorer prognosis (5 years overall survival is 17.8%) when compared to the survival rate of oral cancer without RPLN metastasis (5 years overall survival is 40%). There was no statistically significant difference between the overall survival in primary RPLN metastasis and recurrent RPLN disease.     

PMS2: a potential prognostic protein marker in oral squamous cell carcinoma

Background An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction in exposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors could be contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 protein immunoexpression on the prognosis of patients with OSCC. Material and Methods This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohistochemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed at a 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallis tests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteristics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p<0.05). Results An overexpression of PMS2 was observed in N0/1 tumors and in oral cancers found in unusual locations. In patients ≤60 years of age, high levels of PMS2 ( >60%; p=0.041) were associated with low survival (p=0.029). In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression (p=0.042) significantly increased the risk of death for ≤60 years old patients. Conclusions The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCC patients 60 years of age and younger. Key words:Squamous cell carcinoma, mouth neoplasms, mismatch repair endonuclease PMS2, survival.     

Myofibroblast presence in apparently normal mucosa adjacent to oral squamous cell carcinoma associated with chronic tobacco/areca nut use: evidence for field cancerization

Objective. Myofibroblasts are primary cellular components of activated tumor stroma, associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, their role in field cancerization has not been addressed. This study aims to evaluate the presence of myofibroblasts in patient-matched histologically normal mucosa adjacent to oral squamous cell carcinoma (HNMAOSCC) and OSCC tissues. Materials and methods. Fifty patient-matched tissues of OSCC and HNMAOSCC associated with chronic areca nut/tobacco use were subjected to immunohistochemistry using α-SMA for detection of myofibroblasts. Normal oral mucosa (n = 15) were stained as controls. Results. The number of α-SMA stained myofibroblasts in OSCC and HNMAOSCC were significantly increased as compared to that of the normal controls (p < 0.001). Further, a significant correlation was established for the presence of myofibroblasts in the stroma of OSCC and HNMAOSCC. Conclusions. Myofibroblasts are an early stromal change in the HNMAOSCC, highlighting the possible role of myofibroblasts as likely mediators for field cancerization and their potential use as a field effect marker.     

Connexin 43, Bcl-2, Bax,Ki67, and E-cadherin patterns in oral squamous cell carcinoma and its relationship with GJA1 rs12197797 C/G

Background To our knowledge, there is no useful and accurate prognostic biomarker or biomarkers for patients with oral squamous cell carcinoma (OSCC), a tumor with uncertain biological behavior, and unpredicTable clinical progress. The purposes of this study were: a) to determine the expresión profile of Connexin 43, Bcl-2, Bax, E-cadherin, and Ki67 in patients with OSCC; b) identify the GJCA1 rs12197797 genotypic composition.Material and Methods A cross-sectional study using genomic DNA and biopsy samples extracted from the oral mucosa with/without OSCC, older than 18 years, both genders, attended at Facultad de Odontología, Universidad Nacional Córdoba. Immunostaining for Cx43, Bcl-2, Bax, E-cadherin, and Ki67 and genotyping GJA1 rs12197797 by RFLP were performed. Odds Ratio (95% CI), Spearman Coefficient were estimated. Mann-Whitney test was applied to analyze immunostaining between controls/cases (p <0.05 was set for statistical significance).Results GG (mutant) was the most frequent genotype in patients with OSCC diagnosis (53.2%) in relation to CC “healthy” genotype (p=0.00487; OR=7.33; CI95% [1.1-54.7]). And, the allele G (mutant) had a presence in 75.5% of OSCC patients. However, no significant association was observed between alleles C/G and diagnosis (p=0.0565). The heterozygous genotype was the most frequent in the patients of both groups Cx43 and E-cadherin markers were lower in OSCCs in relation to controls. Ki67 and Bcl-2 immunolabeling were high on OSCC, and Bax immunomarker was diminished in OSCC.Conclusions We hypothesized that the oral epithelium losses Connexin 43 and E-cadherin in the membrane, which modifies cell differentiation. The Ki67 and Bcl2 overexpression would increase the cell density in the tissue, by promoting proliferation and decreasing apoptosis. And, this study shows evidence that patients who carry on allele G of GJA1rs12197797 could be at risk of developing OSCC. Key words:Cx43, E-cadherin, Ki67, Bax, Bcl-2, immunostaining expression profile, GJA1 rs12197797 genotyping.     

Pain is associated with an endophytic cancer growth pattern in patients with oral squamous cell carcinoma before treatment

The origins and mechanisms of pain arising from oral cancer are important. Oral cancer pain impairs a patient’s quality of life. This study was undertaken to elucidate significant risk factors associated with spontaneous pain in patients with untreated oral squamous cell carcinoma (OSCC) before treatment. A total of 113 patients (82 men, 31 women; median age, 64 years) with untreated OSCC were examined. Correlations between spontaneous pain in the primary site and sex, age, primary site, TN stage, clinical stage, and clinical growth type of cancer (exophytic or endophytic), as well as the degree of histological differentiation and the histological mode of invasion were evaluated. At the initial examination, 42 (37%) of patients had spontaneous pain. In univariate statistical analyses, reported pain correlated significantly with patient age and the clinical growth type of the cancer, as well as with the degree of histological differentiation and the histological mode of invasion. Multiple logistic regression analysis showed significant correlations between reported spontaneous pain and the clinical growth type of the cancer (P = 0.0003; odds ratio, 9.5; 95% confidence interval, 2.8-32.3), as well as reported spontaneous pain and the histological mode of invasion (P = 0.0026; odds ratio, 4.7; 95% confidence interval, 1.7-12.7). Clinical and histological endophytic growth patterns of OSCC might be significant risk factors for the presence of spontaneous pain before treatment.     

口腔白斑和鳞癌组织中emsl基因扩增的临床意义

目的：探讨emsl基因在口腔白斑和口腔鳞癌组织中扩增的临床意义。方法：采用显微解剖和差示PCR方法在15例正常口腔黏膜组织，30例口腔白斑组织和33例口腔鳞癌组织中检测emsl扩增，Logistic回归分析其与患者临床病理参数之间的相关关系。结果：emsl扩增与口腔鳞癌原发肿瘤大小T分级（P=0．025）、分化程度（P=0．043）、淋巴结状态（P=0．015）、临床分期（P=0．038）有显著相关性。结论：有emsl扩增的口腔鳞癌患者其预后可能较差，提示emsl扩增对OSCC预后有一定的预测价值。