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The proportion of oral and oropharyngeal squamous cell carcinoma (OOSCC) that can be attributed to human papillomavirus (HPV) infection is growing nowadays. A potential factor indicating the occurrence of HPV-positive OSCC is a change in the degree of methylation of gene promoters that play a key role in the immune response. In this study, we investigated the difference in the methylation of EDARADD, GBP4, HAVCR2, HLA DPB1, IL12RB1, MARCO, and SIGLEC12 gene promoters in samples of healthy oral mucosa versus samples of oral and oropharyngeal cancer. The presence of HPV infection in samples was examined earlier. To determine the difference in methylation of those gene promotors, isolated and bisulfite-modified DNA was analysed by the methylation-specific PCR method. The investigated gene promoters were found to be more hypomethylated in the oral and oropharyngeal cancer samples in comparison to normal tissue. The proportion of unmethylated gene promoters was similar in HPV-positive and HPV-negative cancers, although the data should be confirmed on a larger set of samples. To conclude, in samples of healthy oral mucosa, the investigated gene promoters were found to be methylated in a high percentage (73.3% to 100%), while in oral and oropharyngeal cancer samples, they were methylated in a low percentage (11.1% to 37%), regardless of HPV infection. [ABSTRACT FROM AUTHOR]

• Data on Mi and ITC in the lymph nodes of patients with OOSCC are scarce. • Mi seems to negatively affect the prognosis of patients with OOSCC. • Too few patients with ITC have been studied to draw even definitive conclusions. • The appropriate thresholds to differentiate Mi from ITC in OOSCC are not supported from solid data. An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas. [ABSTRACT FROM AUTHOR]

To date, no valid outcome measure has been developed in European Portuguese (EP) to assess the opinion of the patients with oral and oropharyngeal cancer about the speech impact in his/her related quality of life. This study aimed to cross-culturally adapt the speech handicap index (SHI) in EP and contribute to its validation in oral and oropharyngeal cancer patients. A cross-sectional study was carried out in two phases: (i) SHI translation, back-translation, expert analysis, and pilot study; (ii) application of the EP version of the SHI (EP-SHI) to 95 patients with oral and oropharyngeal cancer and 83 gender- and age-matched healthy individuals. A total of 23 randomly chosen patients were asked to re-fill the EP-SHI questionnaire after 3 weeks. The psychometric properties (feasibility, practicability, reliability, and validity) were assessed. The EP-SHI version brought together expert consensus and the acceptability of 75% of the participants in the pilot study. The EP-SHI questionnaire is feasible (no missing data and floor effect < 7%), practical (an average of 5.5 min to complete), possesses internal consistency reliability (Cronbach's alpha ≥ 0.90), test-retest reliability (interclass correlation coefficient, ICC ≥ 0.90), significantly strong convergent validity with EP-voice handicap index (VHI) (rô≥0.94), distinguishes patients from healthy speakers and within the patients' group according to individual speech rating and glossectomy surgery. The EP-SHI is a culturally relevant, valid and reliable patient reported outcome measure (PROM), and therefore, it is appropriate to be recommended for used with oral and oropharyngeal cancer patients. [ABSTRACT FROM AUTHOR]

Objective: Chemoradiation (CRT) for nonlaryngeal head and neck cancer (HNC) can lead to voice and swallowing dysfunction. The purpose of this study was to examine voice and swallowing from the patient's perspective at least 5 years after treatment. Design: Patient survey. Methods: Twenty-eight patients treated with primary or adjuvant CRT at least 5 years ago (mean = 10.7 years, SD = 5.5, range, 5-28) completed a survey created based on previously validated questionnaires (the Patient Perception of Swallowing Function Questionnaire, PPSFQ; the Eating Assessment Tool, EAT-10; the Voice Handicap Index, VHI-10; the Voice Related Quality of Life, V-RQOL). Results: Patients reported some voice and swallowing dysfunction (39% of V-RQOL scores in categories of fair, poor, or worst possible and 32% of VHI-10 scores ≥20 or greater than 50% of the maximum; 39% of PPSFQ scores greater than 50% of the maximum and 32% of EAT-10 scores ≥20 or 50% of the maximum). There was a correlation between V-RQOL and VHI-10 scores (Pearson product moment correlation coefficient r =.96, calculated probability value p = 0), PPSFQ and EAT-10 scores (r = 0.87, p = 0.8 × 10−8), as well as between V-RQOL and PPSFQ/EAT-10 scores (r =.94, p = 0), VHI-10 and PPSFQ/EAT-10 scores (r =.97, p = 0). Conclusions: Perceived voice and swallowing dysfunction following CRT for nonlaryngeal HNC can persist or worsen beyond 5 years. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the prognoses outcomes of mandibular preservation method (MPM) and the mandibulotomy approach (MLA) in oral and oropharyngeal cancer (OOPC) patients.Method: We searched PubMed, Web of Science, EMBASE, Chinese BioMedical Literature Database (CBM), Cochrane Library, and clinicaltrials.gov up to September 2016 to identify the studies that compared the prognoses of the MPM versus the MLA in OOPC patients. Two authors individually extracted the data and performed quality assessment. The surgical margins, overall survival rate, total and local recurrence rates, fistula formation, and other functional outcomes were evaluated.Result: Six studies with 309 patients were included in our analysis. No significant difference was found regarding the surgical margins, overall survival rate, total and local recurrence rates, and speech and tongue movement between the MPM and MLA groups. However, the MPM group showed a significantly lower fistula formation rate than the MLA group after the operation.Conclusion: These findings suggest that the MPM may provide a similar clinical outcome to the MLA, but that the MPM has a lower complication rate in the treatment of OOPC patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the postoperative platelet count changes in patients with oral and oropharyngeal squamous cell carcinoma undergoing preoperative chemoradiotherapy in order to test the hypothesis that the failure of platelets to recover to normal range within 7 days after surgery represents a significant risk factor for poor survival. Materials and methods: A cohort of 102 patients with primary locally advanced oral and oropharyngeal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy and surgery was retrospectively analyzed. For each patient, platelet counts were evaluated prior to neoadjuvant treatment, prior to surgery and throughout postoperative days 1 to 7. The Kaplan-Meier method and Cox regression models were used to assess the impact of platelet count changes on survival. Results: Overall survival rate at 5 years was 28 % for patients whose platelets did not recover by day 7, with 52 % for patients whose platelets remained within a normal level or recovered to this by day 7 ( p = 0.005). In multivariate analysis, failure of platelet recovery by day 7 was independently associated with shorter overall survival ( p = 0.03). Conclusions: We demonstrated that the failure of platelets to recover to normal range by the seventh postoperative day is an independent adverse prognostic factor in patients with oral and oropharyngeal cancer undergoing neoadjuvant treatment and surgery. Clinical relevance: Our results indicate that physicians should pay closer attention to monitoring the postoperative platelet count course, as it may predict the clinical outcome of patients with oral and oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The hepatocellular carcinoma-related protein 1 (HCRPI) is a key factor in the degradation of the epidermal growth factor receptor. In this study, we assessed the prognostic significance of HCRP1 expression in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). METHODS: HCRP1 expression was determined by immunohistochemistry on tissue biopsy sections of III patients with locally advanced OOSCC undergoing neo-adjuvant chemoradiotherapy followed by surgery. The Kaplan-Meier method and Cox regression models were used for survival analyses. RESULTS: Low HCRP1 expression was associated with poor recurrence-free survival (P = 0.046) and overall survival (P = 0.03). Multivariate analysis revealed that low HCRP1 expression remained an independent risk factor for relapse (HR 2.98, 95% CI 1.19-7.49, P = 0.02) and death (HR 3.04, 95% CI 1.19-7.79, P = 0.02). CONCLUSION: Low HCRP1 expression was found to be of adverse prognostic significance in patients with OOS-CC who received preoperative chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Current CT-protocols for staging oral and oropharyngeal cancer include primary transversal slices and secondary tilted slices to avoid artifact-producing regions of dental metalwork. Some of the latest MDCT scanners do not allow gantry tilt. Hence, we assessed the relevance of secondary tilted slices in tumor staging. Materials and methods: Scans of a tiltable 64-row MDCT-scanner of 82 patients with oral or oropharyngeal cancer were retrospectively and independently evaluated twice by three readers: once using the primary transversal scans only, and once taking the transversal and secondary tilted scans into account. Tumor diameters and TN-stage were determined with both methods. Artifacts on transversal scans were analyzed using a 3-point-ranking-scale. Results: Image quality was impaired by severe artifacts in 24% of transversal slices of the oral cavity and in 12% of the oropharynx. The three readers detected an average of 57.7±2.1 of 82 tumors (70%) on transversal CT slices. An average of 6.3±0.6 more tumors (8%) were detected when transversal studies were evaluated in conjunction with secondary tilted slices, leading to a significantly (p =0.0156–0.0313) increased average detection rate of 64.0±2.0 tumors (78%). Moreover, secondary tilted slices led to a correction of underestimated tumor stages in up to six patients (7.3%). Conclusion: Tilted slices that avoid artifact-producing regions of dental metalwork significantly improve the reader''s sensitivity and are of incremental value for staging of oral and oropharyngeal cancers. [Copyright &y& Elsevier]

Treatment of oral and oropharyngeal cancer may cause dysphagia. Purpose is to examine whether cine magnetic resonance imaging (MRI) yields additional information compared to standard examination in the evaluation of posttreatment dysphagia and mobility of oral and oropharyngeal structures. Thirty-four cine MRIs were made in 23 patients with advanced oral and oropharyngeal cancer, consisting of an MR image every 800 ms during swallowing which is compared to videofluoroscopy and quality of life questionnaires. A scoring system was applied to assess mobility on cine MR and videofluoroscopy leading to a score ranging from 9 to 17. Cine MRI of the swallowing in a midsagittal plane visualized the tumor (if located in the same plane), important anatomic structures and surgical reconstructions. Posttreatment mobility on cine MRI and videofluoroscopy was significantly diminished compared to pretreatment, mean pretreatment cine MRI score was 10.8 and posttreatment 12.4 ( p = 0.017). Impaired mobility on cine MRI was significantly correlated to more swallowing problems (Spearman's correlation coefficient 0.73, p = 0.04), on videofluoroscopy not. Cine MRI is a promising new technique as an adjunct to standard examinations for evaluation of swallowing in patients with oral and oropharyngeal cancer. Cine MRI directly visualizes the dynamics of swallowing and allows evaluation of pre- and posttreatment differences. Abnormal findings are significantly correlated with subjective swallowing complaints of patients. [ABSTRACT FROM AUTHOR]

Summary: Evidence indicates that allogenic packed red blood cell transfusion results in the host’s immunomodulation, and is associated with adverse clinical outcomes after surgery. The aim of this study was to test whether allogenic leukocyte-depleted blood transfusion represents a significant risk factor for postoperative morbidity after oral and oropharyngeal cancer surgery. A total of 142 patients, diagnosed for the first time with oral and oropharyngeal squamous cell carcinoma, and receiving neoadjuvant chemoradiotherapy followed by surgery between 2000 and 2008 were retrospectively included in this study. Univariate and multivariate logistic regression models were calculated to identify predictors of postoperative complications. We found a significantly higher complication rate in the group of transfused patients compared to patients not exposed to transfusion (complication rate of 84% and 39%, respectively, p <0.001). On multivariate analysis, the amount of packed red blood cells transfused (for 1–4units transfused: adjusted OR, 2.59; 95% CI, 1.24–5.39; p =0.011; for more than >4units transfused: adjusted OR, 5.29; 95% CI, 2.01–13.88; p =0.001) and Charlson’s comorbidity score ⩾1 (adjusted OR, 2.81; 95% CI, 1.38–5.70; p <0.004) were independently associated with the development of postoperative complications. Allogenic leukocyte-depleted blood transfusion is independently associated with increased postoperative complications in patients undergoing surgery for oral and oropharyngeal cancer. This association follows a dose–response relationship, as patients who received larger amounts of packed red blood cells showed a significant trend toward higher postoperative morbidity. [Copyright &y& Elsevier]

J Oral Pathol Med (2012) 41: 40-46 Background: The purpose of this study was to evaluate whether the immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 can predict therapy response and survival in patients with oral and oropharyngeal squamous cell carcinoma treated with preoperative chemoradiation. Methods: Biomarker expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded pretreatment biopsies of 111 homogenously treated patients. We assessed the association between clinicopathological variables including response to neoadjuvant chemoradiotherapy as well as the survival of the patients and the expression of the biomarkers as both dichotomized (positive vs. negative) and continuous variables. Results: Biomarker overexpression on the basis of pre-selected cutoff points was seen in 66 of 111 (59%) cases for p53, in 77 (69%) for p21, in 48 (43%) for p27, in 81 (73%) for cyclin D1, and in 54 (49%) cases for Ki67, respectively. None of the examined biomarkers was able to predict response to neoadjuvant chemoradiotherapy or was associated with survival outcome. Post-treatment pathologic TNM stage ( P < 0.001), pathologic response ( P < 0.001), and perineural invasion ( P < 0.001) were the only factors having a significant effect on recurrence-free survival. Post-treatment pathologic N stage ( P = 0.005), post-treatment pathologic TNM stage ( P < 0.001), pathologic response ( P < 0.001), and perineural invasion ( P = 0.001) had a significant impact on overall survival. Conclusions: Our results suggest that the biomarkers p53, p21, p27, cyclin D1, and Ki67 have no impact on treatment response and survival in patients with oral and oropharyngeal cancer treated with preoperative chemoradiation. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to determine the value of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative assessment of mandibular invasion in squamous cell carcinomas (SCC), adjacent or fixed to the mandible. DCE-MRI was performed with gadolinium diethylene triamine pentaacetic acid (Gd-DTPA). Data were obtained from 25 patients. From pharmacokinetic analysis of the tissue uptake of Gd-DTPA, the DCE-MRI parameters (k ep, K trans and v e) were determined, with k ep representing the exchange rate constant, K trans the volume transfer constant and v e the volume of extracellular space per unit volume of tissue. The histology of the resection specimens was used as gold standard for the extent of mandibular invasion. SCC with medullary invasion showed higher mean k ep and K trans compared with SCC without medullary invasion (ANOVA, p <0.001). ROC analysis of k ep and K trans revealed reliable threshold values for medullary invasion. In conclusion, DCE-MRI can discriminate SCC with medullary invasion from SCC without medullary invasion and may serve as a valuable tool in preoperative tumour staging with regard to the delineation of medullary invasion. [Copyright &y& Elsevier]

Summary: Treatment of the clinical N0 neck in squamous cell carcinoma (SCC) of oral cavity and oropharynx remains a dilemma. None of the current imaging modalities are able to detect the presence of micrometastases in the lymph nodes of clinical N0 necks reliably. The aim of this study was to determine the diagnostic properties of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) in patients clinically staged as N0. FDG PET results of 38 patients were compared to histologic specimens obtained with neck dissections or to follow-up. FDG PET performance was compared to computed tomography (CT), magnetic resonance imaging (MRI) or ultrasonography-guided fine needle aspiration cytology (USgFNAC). Sensitivity and specificity of FDG PET in detecting occult cervical metastases were 50% and 97% respectively. Although FDG PET performed better than conventional imaging modalities, sensitivity was lower than desired. As a consequence, clinical application of FDG PET in the patient staged as N0 is limited. [Copyright &y& Elsevier]

Summary: Histopathological assessment of the surgical resection specimen continues to provide information that is central to determining the post-operative treatment needs and prognosis for an individual patient with oral/oropharyngeal squamous cell carcinoma. This review describes the prognostic value of histopathological features related to the primary tumour and the cervical lymph nodes, and considers their relative merits. In addition, a brief overview of more general patient factors is included. Throughout the review, guidance is offered on practical aspects of the histopathological assessment together with brief mention of potential inaccuracies. Emphasis is given also to the importance of the partnership between the surgeon and the pathologist, the need for standardisation during all stages of the histopathological assessment, and the value of accurate documentation of the findings. [Copyright &y& Elsevier]

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000–2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38–2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41–2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12–1.88, p = 0.005 and HR 1.42, 95% CI 1.14–1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10–2.43, p = 0.014 and HR 1.55, 95% CI 1.12–2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to evaluate the prognostic significance of the pre- treatment C-reactive protein (CRP) level in a cohort of 503 patients with oral and oropharyngeal cancer treated at a tertiary academic center between 2000 and 2017. Cancer-specific survival (CSS), overall survival (OS) and loco-regional control (LC) were calculated using Kaplan-Meier analysis. To evaluate the prognostic value of the CRP level for the clinical endpoints, univariate and multivariate Cox regression models were applied. The median follow-up period was 61 months. Patients were divided into elevated CRP (≥5 mg/L) and normal CRP groups, according to pre-treatment plasma levels. An increased CRP level was significantly associated with shorter CSS (p < 0.001, log-rank test), as well as with shorter OS (p < 0.001, log-rank test) and loco-regional control (p = 0.001, log-rank test). In addition, multivariate analysis identified CRP as an independent predictor for CSS (hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.08–2.35; p = 0.020) as well as for OS (HR 1.62, 95%CI 1.17–2.24; p = 0.004) and LC (HR 1.50, 95%CI 1.06–2.14; p = 0.023). In subgroup analysis, Kaplan Meier curves revealed that an elevated pre-treatment CRP level was a consistent prognostic factor for poor CSS (p = 0.003, log-rank test), OS (p = 0.001, log-rank test), and LC (p = 0.028, log-rank test) in patients treated with definitive (chemo-) radiotherapy, whereas a significant association in patients undergoing surgery and postoperative radiotherapy was not detected. The pre-treatment CRP level seems to represent a prognostic factor for CSS, OS, and LC in patients with oral and oropharyngeal cancer, particularly in those treated with definitive (chemo-) radiotherapy. Additional large-scale prospective studies are warranted to confirm and extend our findings. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to evaluate feasibility, reliability, validity of the SWAL-QOL (a questionnaire on swallowing problems in daily life), and to define sample size calculations and a clinically relevant cut-off score. One hundred and two patients were treated for cancer of the oral cavity or pharynx and 111 healthy subjects completed the SWAL-QOL and the EORTC H and N35 questionnaire. A randomly selected subset of patients (n =29) completed the SWAL-QOL twice to assess test–retest stability. For the patient sample, data on tumor site (oral or oropharyngeal) and stage (I–IV), treatment modality (surgery, radiation, surgery+radiation, chemoradiation), and presence of a PEG tube were abstracted from medical records. Reliability of the SWAL-QOL was high with high internal consistency and test–retest stability. Feasibility was good, except for patients with tube feeding, of whom 38% did not complete the questionnaire (versus 9% of those with oral feeding). A cut-off score of 14 points (or higher) was defined regarding the total SWAL-QOL score to identify patients with swallowing problems with 94% sensitivity and 84% specificity. A difference score of 12 points or more is proposed to be used in study designs with multiple groups. It can be concluded that the SWAL-QOL is a feasible, reliable, and valid questionnaire to assess patients’ swallowing impairment. It can be used in future comparative studies for oral and oropharyngeal cancer and in clinical practice to identify patients in need of further diagnostics and/or swallowing rehabilitation services. [Copyright &y& Elsevier]