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Objectives: This study aimed to investigate the association between salivary matrix metalloproteinase‐1 (MMP‐1) and clinicopathological parameters of oral cavity squamous cell carcinoma (OSCC) and compare the prognostic efficacy of salivary MMP‐1 and other established circulating markers for OSCC. Methods: Saliva specimens from 479 OSCC subjects were examined using an enzyme‐linked immunosorbent assay. The area under the curve (AUC) values of salivary MMP‐1 and other markers were calculated, and survival analyses were conducted using Kaplan–Meier and multivariate regression methods. Results: Salivary MMP‐1 showed good discrimination in predicting overall survival, with an AUC of 0.638, which was significantly higher than that of albumin (0.530, p =.021) and Charlson comorbidity index (0.568, p =.048) and comparable with neutrophil‐to‐lymphocyte ratio (0.620, p =.987), platelet‐to‐lymphocyte ratio (0.575, p =.125), and squamous cell carcinoma antigen (0.609, p =.605). Elevated levels of salivary MMP‐1 were significantly associated with higher pT classification, pN classification, overall pathological stage, positive extranodal extension, tumor differentiation, positive lymphovascular invasion, positive perineural invasion, and tumor depth (p all <.05). Multivariate analyses indicated that a higher level of salivary MMP‐1 (≥2060.0 pg/mL) was an independent predictive factor of poorer overall survival (adjusted hazard ratio: 1.421 [95% confidential interval: 1.014–1.989], p =.041). Conclusion: The study found that the salivary MMP‐1 level was significantly associated with many adverse clinicopathological parameters of OSCC. In OSCC, it was found to have superior efficacy in predicting prognosis and was an independent prognostic factor of post‐treatment outcome. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

Objectives: Lymph node burden has been proposed to estimate the cumulative adverse effect of nodal metastasis. In this study, a meta‐analysis was conducted to evaluate the prognostic value of lymph node burden in oral cavity squamous cell carcinoma. Study Designs: Systemic review and meta‐analysis. Methods: PubMed, EMBASE and the Cochrane Library as well as manual searches were performed until April 2020. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival, disease‐specific survival, and disease‐free survival were extracted and pooled. Results: Eleven included studies were published between 2009 and 2019. The cumulative number of patients was 20,607 (range 35–14,554). Extranodal extension was adjusted or evaluated in all of the studies. The meta‐analysis indicated that a higher lymph node burden was significantly related to worse overall survival (HR 2.62, 95% CI 2.12–3.25), worse disease‐specific survival (HR 3.14, 95% CI 1.85–5.33) and worse disease‐free survival (HR 2.30, 95% CI 1.62–3.26). The highest hazard ratio was observed when the cutoff value was 3 for overall survival, 3 for disease‐specific survival, and 4 for disease‐free survival. The hazard ratio showed an upward trend before the cutoff value of 3 but no significant incremental change when the cutoff exceeded 3. Conclusions: In oral squamous cell carcinoma, lymph node burden is an independent prognosticator for survival outcomes. However, more prospective or high‐quality studies are required to determine the optimal cutoff. Level of Evidence: NA Laryngoscope, 132:88–95, 2022 [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To elucidate the associations among the immunohistochemical expression of tumor markers, clinicopathological variables, and disease-free survival (DFS) in patients with early-stage glottic squamous cell carcinoma (SCC) who underwent transoral laser microsurgery (TLM) as the primary treatment.Study Design: Retrospective chart review.Methods: The records of consecutive patients with Tis-T2N0 glottic SCC who underwent TLM between August 1, 2012 and October 31, 2015 were reviewed. Expression of Bcl-2, pRB, p16INK4A , p53, c-Myc, E-cadherin, and EGFR was examined using tissue microarrays containing tumor specimens through immunohistochemistry. Three-year DFS rates were calculated.Results: A total of 65 consecutive patients were identified, of which 28 were excluded due to insufficient tissue (n = 22) and low biomarker quality (n = 6). Therefore, 37 patients with complete records were included. The included patients were significantly older and had a more advanced type of cordectomy than did the excluded patients (P = .015 and .009, respectively). According to the findings of univariate analysis, age, betel quid chewing, type of cordectomy, BCL-2 expression, and pRB expression significantly predicted 3-year DFS. According to the findings of multivariate analysis, age (adjusted hazard ratio: 0.94, 95% CI: 0.88-1.00), betel quid chewing (adjusted hazard ratio: 5.07, 95% CI: 1.32-19.44), and pRB expression (adjusted hazard ratio: 0.02, 95% CI: 0.00-0.28) were independent predictors of 3-year DFS.Conclusions: Low pRB expression is a potential biomarker for predicting disease relapse after primary TLM for early-stage glottic SCC and may help to identify high-risk patients who can subsequently undergo intensive management.Level Of Evidence: 4 Laryngoscope, 129:E220-E226, 2019. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: The role of tumor-associated tissue eosinophilia (TATE) in oral cavity cancer remains quite controversial. This study investigated the potential role of TATE in tongue squamous cell carcinoma (TSCC).Study Design: Retrospective case series.Methods: This study retrospectively enrolled 259 consecutive TSCC patients who underwent surgery between July 2004 and December 2015. Histopathological examinations for TATE in TSCC tumors were reviewed, and the association of TATE with different clinicopathological factors was evaluated. A nomogram was generated based on several major clinicopathological factors and TATE to improve the accuracy of prognostic prediction.Results: Higher levels of TATE were significantly associated with male sex, alcohol consumption, cigarette smoking, higher pT classification, advanced disease stage, and tumor depth (P = .006, .003, .024, .041, .013 and .006, respectively). Our results indicated that extranodal extension, cell differentiation, and TATE were independent predictors of overall survival (P < .001, .004, and .032, respectively) and disease-free survival (P < .001, .012, and .013, respectively). TATE levels significantly correlated with circulating eosinophils (r = 0.139, P = .040), and the c-index of our nomogram foroverall survival was 0.786, which demonstrates better accuracy in prognosis prediction than the TNM stage only (c-index = 0.738).Conclusions: Higher levels of TATE were associated with several clinicopathological factors and poorer survival rates, and a nomogram incorporating TATE levels may strengthen the prediction accuracy of prognosis in TSCC patients.Level Of Evidence: 4 Laryngoscope, 129:1123-1129, 2019. [ABSTRACT FROM AUTHOR]

Background: We sought to compare the prognostic significance of different preoperative complete blood count cell ratios in patients with oral cavity squamous cell carcinoma (OSCC) treated with surgery and postoperative radiotherapy (PORT). Methods: We retrospectively reviewed the clinical records of 890 patients with OSCC who were treated with surgery and PORT. The following preoperative complete blood count cell ratios were collected: neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and lymphocyte‐to‐monocyte ratio (LMR). Overall survival (OS), local control, regional control, and distant control (DC) served as the main outcomes of interest. Results: The results of multivariate analysis in the entire study cohort revealed that a low NLR was the only independently favorable marker of both OS (adjusted hazard ratio [HR]: 0.794, 95% confidence interval (CI): 0.656–0.961, bootstrap p = 0.028) and DC (adjusted HR: 0.659, 95% CI: 0.478–0.909, bootstrap p = 0.015). Both LMR and PLR were not retained in the model as independent predictors. Subgroup analyses in high‐risk patients (i.e., those bearing T4 disease, N3 disease, or poor differentiation) revealed that a high NLR was a significant adverse risk factor for both OS and DC (all p < 0.03)—with a borderline significance being evident for DC in patients with T4 disease (p = 0.058). Conclusions: A high pretreatment NLR was an independent unfavorable risk factor for both OS and DC in patients with OSCC who underwent surgery and PORT. No other preoperative complete blood count parameters and cell ratios were found to have prognostic significance. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognostic value of the preoperative systemic immune‐inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC‐SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT). Materials and Methods: We retrospectively reviewed the clinical records of patients with OC‐SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden's index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC). Results: The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p < 0.001). No independent association between SII and LC/RC was observed. Conclusion: Increased SII values predict poor DC and OS in patients with OC‐SCC treated with curative resection and adjuvant RT/CCRT. Owing to the higher risk of systemic failure in this patient group, a thorough follow‐up surveillance schedule may be advisable pending independent confirmation of our data. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the association between preoperative glycated hemoglobin (HbA1c) levels and the treatment outcomes of oral cavity squamous cell carcinoma (OSCC). Methods: Three hundred and fifty‐eight OSCC patients were consecutively enrolled between July 2004 and July 2016. Clinicopathological parameters and survival outcomes were analyzed following HbA1c stratification of 6.5% (HbA1c ≥ 6.5%: n = 74, 20.6%) and 7.0% (HbA1c ≥ 7.0%: n = 53, 14.8%). Results: Higher HbA1c levels were associated with elevated body mass index, lower albumin levels, wider surgical margins, and prolonged hospital stays (HbA1c 6.5%: p =.001,.048,.030,.009, respectively; HbA1c 7.0%: p =.092,.032,.009,.015, respectively). Survival rates stratified by HbA1c 6.5% were as follows: locoregional recurrence‐free survival, p =.014; distant metastasis‐free survival, p =.013; second primary cancer‐free survival, p =.015; overall survival, p =.014; disease‐specific survival, p =.002 and HbA1c 7.0%: locoregional recurrence‐free survival, p =.013; distant metastasis‐free survival, p =.013; second primary cancer‐free survival, p =.014; overall survival, p =.015; disease‐specific survival, p =.004. Multivariate analyses identified HbA1c as an independent prognostic factor for overall and disease‐specific survival (HbA1c 6.5%: p =.014 and.002, respectively; HbA1c 7.0%: p =.036 and.013, respectively). Conclusions: Oral squamous cell carcinoma patients with higher preoperative HbA1c levels had longer hospitalization and worse survival outcomes. [ABSTRACT FROM AUTHOR]

Objective: There is no useful tool to clinically predict the occurrence of osteoradionecrosis (ORN) of the mandible quantitatively. The aim was to investigate the risk factors, including different modalities of radiotherapy, for developing mandibular ORN in patients undergoing marginal mandibulectomy and postoperative radiotherapy.Methods: Between January 2006 and December 2012, 167 subjects who underwent marginal mandibulectomy and postoperative radiotherapy with different modalities were enrolled. The association of ORN with mandibular bone measurements and patient variables was analyzed, and a nomogram was established.Results: Fifteen (8.98%) of the 167 patients developed ORN during the follow-up period, and ORN was significantly associated with diabetes mellitus (DM), body mass index (BMI), remaining bone height, remaining bone height to original bone height ratio, resected bone height to original bone height ratio, and mandibular dose (P: < 0.001, 0.004, 0.042, 0.018, 0.010, 0.020, respectively). Interestingly, the risk of ORN had no significant difference between conformal and intensity modulation radiation therapy (P = 0.407). Multivariate analysis revealed that DM and resected bone height to original bone height ratio ≥ 50% were independent risk factors for postoperative ORN. A nomogram consisting of BMI, DM, resected bone height to original bone height ratio, mandibulotomy, and mandibular dose for predicting the ORN-free probability was established; and the c-index of the nomogram for ORN status was 0.803.Conclusion: A nomogram based on the risk factors was plotted to strengthen the prediction of ORN quantitatively. Surgeons should be more discrete regarding the treatment plan for patients with higher probability of ORN.Level Of Evidence: 3b Laryngoscope, 130:101-107, 2020. [ABSTRACT FROM AUTHOR]

Background: Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies. Methods: Recent, relevant peer‐reviewed evidence were critically reviewed and summarized. Results: This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed. Conclusion: Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies. [ABSTRACT FROM AUTHOR]

Approximately, 25% of nasopharyngeal carcinoma (NPC) patients develop recurrent disease. NPC may involve relatively few genomic alterations compared to other cancers due to its association with Epstein‐Barr virus (EBV). We envisioned that in‐depth sequencing of tumor tissues might provide new insights into the genetic alterations of this cancer. Thirty‐three NPC paired tumor/adjacent normal or peripheral blood mononuclear cell samples were deep‐sequenced (>1000×) with respect to a panel of 409 cancer‐related genes. Newly identified mutations and its correlation with clinical outcomes were evaluated. Profiling of somatic mutations and copy number variations (CNV) in NPC tumors identified alterations in RTK/RAS/PI3K, NOTCH, DNA repair, chromatin remodeling, cell cycle, NF‐κB, and TGF‐β pathways. In addition, patients harbored CNV among 409 cancer‐related genes and missense mutations in TGF‐β/SMAD signaling were associated with poor overall survival and poor recurrence‐free survival, respectively. The CNV events were correlated with plasma EBV copies, while mutations in TGFBR2 and SMAD4 abrogate SMAD‐dependent TGF‐β signaling. Functional analysis revealed that the new TGFBR2 kinase domain mutants were incapable of transducing the signal, leading to failure of phosphorylation of SMAD2/3 and activation of downstream TGF‐β‐mediated cell growth arrest. This study provides evidence supporting CNV and dysregulated TGF‐β signaling contributes to exacerbating the NPC pathogenesis. [ABSTRACT FROM AUTHOR]

Background: The prognostic relevance of extranodal extension (ENE) for salivary gland carcinoma (SGC) remains unclear. The present study is undertaken to investigate the predictive significance of pathological nodal parameters in surgically treated patients with nodal metastatic SGC. Methods: This multicenter cohort included 114 patients with pathologically proven node‐positive SGC between 2000 and 2014. Possible correlations of clinicopathological parameters and outcomes were examined. Results: The median follow‐up was 69 months (range, 11‐173 months). The multivariate analysis identified metastatic node number (1‐2 vs 3‐6; 1‐2 vs ≥7) as an independent predictor for regional control (P = 0.005; P = 0.02), locoregional control (P = 0.008; P = 0.04), distant metastasis‐free survival (P = 0.17; P = 0.006), disease‐free survival (P = 0.05; P = 0.002), and overall survival (P = 0.18; P = 0.009), whereas ENE was not associated with survival outcomes. Conclusions: Metastatic node number, not ENE, is an independent node‐related prognosticator for SGC. Integration of ENE into the American Joint Committee on Cancer 8th edition staging criteria may not improve prognostic performance. [ABSTRACT FROM AUTHOR]

Abstract: Background: The purpose of this study was to elucidate the clinicopathological associations and molecular mechanisms of karyopherin alpha 2 (KPNA2) in oral cavity squamous cell carcinoma (SCC) progression. Methods: The KPNA2 expressions were analyzed by immunohistochemistry and enzyme‐linked immunosorbent assay in 209 tissues and 181 saliva samples, respectively. The functions of KPNA2 in migration and invasion were examined in KPNA2‐knowdown cells. The matrix metalloproteinase (MMP) levels were determined by real‐time quantitative polymerase chain reaction (qPCR). The subcellular fraction was used to obtain the nuclear distribution of nuclear factor‐kappa B (NF‐κB). Results: The KPNA2 overexpression was associated with extranodal extension (P < .05) and poor disease‐specific survival in patients with oral cavity SCC (P < .05). The salivary KPNA2 levels were elevated in patients with oral cavity SCC (P < .05). The KPNA2 knockdown reduced cell migration and invasion. This knockdown also suppressed the interleukin (IL)‐1β‐induced nuclear import of NF‐κB and MMP (MMP‐1, MMP‐3, and MMP‐9) transcription. Conclusion: The KPNA2 overexpression is an independent biomarker for poor prognosis of oral cavity SCC and is required for MMP‐mediated metastasis. [ABSTRACT FROM AUTHOR]

Abstract: We aimed to investigate the prognostic significance of combined pretreatment lymphocyte counts (LCs) and body mass index (BMI) in patients with head and neck cancer (HNC) treated with radiation therapy (RT). Nine hundred and twelve patients with HNC who were treated with RT were retrospectively reviewed. Survival was analyzed by stratifying the patients according to pretreatment LCs and BMI. Patients with low pretreatment LCs and BMI were characterized by a more advanced T stage, fewer nasopharyngeal subsites, less smoking and drinking, and fewer comorbidities. Patients with low pretreatment LCs and BMI had a significantly poorer overall and distant metastasis‐free survival than those with high pretreatment LCs and BMI. No significant differences were observed in terms of local or regional recurrence‐free survival. Combined pretreatment LCs and BMI may be more effective at predicting overall and distant metastasis‐free survival in patients with HNC treated with RT. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to investigate the potential prognostic role of the oral cancer systemic inflammation score (SIS) based on serum albumin levels and the lymphocyte-to-monocyte ratio in patients with oral squamous cell carcinoma (OSCC) after treatment. Study Design A retrospective cohort study. Setting Tertiary care center. Subjects and Methods The study involved 613 patients who were treated for OSCC between September 2005 and December 2014. The association of the oral cancer SIS with various clinicopathological features was investigated. A nomogram based on different clinicopathological features and SIS was established to predict prognosis. Results Higher SIS was significantly associated with older age ( P = .0013), advanced tumor status ( P < .0001), tumor depth ( P < .0001), advanced overall pathologic stage ( P < .0001), and extranodal extension ( P = .0045), as well as the presence of perineural invasion ( P = .0341). Higher SIS, older age, overall stage, and extranodal extension were demonstrated to be independent prognostic indicators for shorter overall survival ( P < .0001). A nomogram comprising SIS, TNM stage, and the degree of cell differentiation, as well as perineural invasion and extranodal extension, was developed to predict the prognosis of these patients. The c-index of the nomogram model based on TNM staging only was 0.688 and could be increased to 0.752 if SIS and several other clinicopathological parameters were incorporated. Conclusions Higher SIS is associated with many poor prognosticators, and the nomogram that was established and based on the incorporation of SIS might strengthen the prediction of prognosis in patients with OSCC. [ABSTRACT FROM AUTHOR]

Abstract: We aimed to determine whether body composition assessment before treatment can predict outcomes in patients with head and neck cancer (HNC). All 881 patients with locoregional head and neck cancer treated with curative intent radiotherapy (RT) between 2005 and 2012 were retrospectively investigated. Body composition was analyzed via pre‐RT planning computed tomography (CT) images. Subcutaneous adipose tissue (SAT) and skeletal muscle (SM) indices were measured cross‐sectionally at the level of the third thoracic vertebra. Overall survival (OS), locoregional control (LRC), and distant metastasis‐free survival (MFS) were analyzed by body composition index and body mass index (BMI). Survivors were followed up for a median of 4.68 years. The SAT indices in female patients were significantly higher than those in males (P < 0.001). The median SAT and muscle indices were 18.6 and 34.3 cm2/m2 for women and 6.19 and 51.74 cm2/m2 for men, respectively. The 5‐ and 10‐year MFS, LRC, and OS rates were 83% and 82.1%, 73.4% and 71.4%, and 66.4 and 57.6%, respectively. Higher pretreatment SAT index was associated with MFS (hazard ratio [HR]: 0.65; P = 0.015), LRC (HR: 0.758; P = 0.047), and OS (HR: 0.604; P < 0.001). Higher pretreatment BMI was associated with MFS (HR: 0.642; P = 0.031) and OS (HR: 0.615; P < 0.001). The pretreatment SM index had no significant effect on MFS, LRC, and OS. Multivariate analysis revealed that T‐stage, N‐stage, lesion sites, age, and RT treatment days are independent factors associated with OS; T‐stage, N‐stage, and lesion sites are independent factors associated with MFS; and N‐stage, smoking history, and betel quid chewing history are independent factors associated with LRC. A higher CT‐assessed SAT index predicts superior MSF, LCR, and OS in patients with curative HNC, whereas SM does not predict survival or locoregional control. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the recovery kinetics of voice and quality of life (QOL) over time in patients with early glottic cancer who underwent transoral laser microsurgery (TLM). Methods A prospective cohort study was conducted in which acoustic and aerodynamic voice assessments and QOL analyses were done using health-related questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions [EORTC-QLQ-C30] and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35-questions [EORTC-QLQ-H&N35]) were administered at designated times. Results Most voice laboratory parameters worsened during the first month, then recovered to baseline after 6 months. The QLQ-H&N35 speech subscale was significantly improved. Among the voice laboratory parameters, pretreatment harmonics-to-noise ratio was an independent predictor ( P = .041) for improvement on the speech subscale at the endpoint. Conclusion Despite an initial deterioration of voice and QOL in the first month, patients who underwent TLM recovered to a plateau since the sixth month and then to better than preoperative status afterward. A greater improvement in QOL was seen in patients with poorer baseline voice quality. [ABSTRACT FROM AUTHOR]

We aimed to compare the overall survival ( OS) of patients with bone metastases ( BM) from solid tumors after standard-dose radiotherapy ([ RT]; 30 Gy administered in 10 fractions; EQD2Gy = 32.5 Gy) and dose-escalated RT (EQD2Gy > 32.5 Gy). We retrospectively reviewed the clinical charts of 1795 patients (median age, 62.3 years; age range, 18-96 years) with BM from solid tumors who were referred for RT to our institute between 2000 and 2013. These patients were assigned to the standard-dose ( n = 1125; 63%) and dose-escalated ( n = 670; 37%) RT groups. OS, estimated as the duration between the first RT session and death, served as the main outcome measure. The dose-escalated RT group had a significantly better OS than the standard-dose RT group ( P = 0.000). After allowing potential confounders in multivariate analysis, the RT dose retained its independent association with OS (hazard ratio [ HR], 0.837; 95% confidence interval [ CI], 0.753-0.929, P = 0.001). After propensity score matching of the baseline characteristics of both groups, RT dose retained its independent association with OS ( HR, 0.887; 95% CI, 0.737-0.951; P = 0.011) on multivariate analysis. Dose-escalated RT exerted more favorable effects on OS in patients with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. Dose-escalated RT was significantly associated with better OS in patients with BM from solid malignancies, particularly among those with non-lung cancer, those without multiple metastases, those without symptoms, and those with favorable prognosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Mutations in the human telomerase reverse transcriptase (TERT) promoter contribute to increased TERT activity. The purpose of the present study was to assess the prevalence of TERT promoter mutations in oral cavity squamous cell carcinoma (SCC). Methods Total DNA was extracted from 201 oral cavity SCC tumors and adjacent normal tissues. Primers were used to amplify the sequence region containing 2 TERT promoter mutations (C228T and C250T) that were then sequenced using the Sanger method. Results Sequencing revealed that 52.5% (104/201) and 12.9% (26/201) of oral cavity SCC tumor tissues and 6.0% (12/201) and 2.5% (5/201) of adjacent normal tissues contained C228T and C250T mutations, respectively. In addition, the C228T mutation was significantly associated with betel nut chewing. Conclusion Our results show that mutations in the TERT promoter occur in patients with oral cavity SCC at a high frequency. This suggests that somatic TERT promoter mutations could play a vital role in the pathogenesis and progression of oral cavity SCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1131-1137, 2017 [ABSTRACT FROM AUTHOR]

ABSTRACT Background The purpose of this study was to test the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting recurrence risk of major salivary gland carcinoma in an Asian cohort. Methods We retrospectively enrolled 149 patients who had undergone intended curative resections for major salivary gland carcinoma between 2007 and 2012. The performance of the MSKCC nomogram and the American Joint Committee on Cancer (AJCC) seventh staging system in predicting recurrence risk was compared. Results The MSKCC nomogram and the AJCC staging system both accurately predicted the 5-year recurrence probabilities, with the concordance index (c-index = 0.82; 95% confidence interval [CI], 0.75-0.89 vs c-index, 0.77; 95% CI, 0.68-0.87; p = .45) in patients with major salivary gland carcinomas after curative surgeries. Comparing to the actual observed events, the calibration plot indicated that the MSKCC nomogram accurately estimated the recurrence in low-risk groups but tended to overestimate in high-risk groups. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the prediction was very good for patients with AJCC stages I and II disease (c-index = 0.92 and 0.90, respectively) and modest for those of AJCC stages III and IVa (c-index = 0.51 and 0.62, respectively). Conclusion The MSKCC nomogram and the AJCC staging system each had its value in predicting recurrence of major salivary gland cancers. When using the MSKCC nomogram to predict the 5-year recurrence-free probability in each AJCC stage, the MSKCC nomogram was more accurate in predicting recurrence risks in those patients with AJCC stage I and II diseases than those with late-stage diseases. © 2017 Wiley Periodicals, Inc. Head Neck 39: 860-867, 2017 [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Plasma Epstein-Barr virus (EBV) DNA concentrations predict prognosis in patients with nasopharyngeal carcinoma (NPC). Recent evidence also indicates that intratumor heterogeneity on F-18 fluorodeoxyglucose positron emission tomography (18 F-FDG PET) scans is predictive of treatment outcomes in different solid malignancies. Here, we sought to investigate the prognostic value of heterogeneity parameters in patients with primary NPC.Study Design: Retrospective cohort study.Methods: We examined 101 patients with primary NPC who underwent pretreatment 18 F-FDG PET/computed tomography. Circulating levels of EBV DNA were measured in all participants. The following PET heterogeneity parameters were collected: histogram-based heterogeneity parameters, second-order texture features (uniformity, contrast, entropy, homogeneity, dissimilarity, inverse difference moment), and higher-order (coarseness, contrast, busyness, complexity, strength) texture features.Results: The median follow-up time was 5.14 years. Total lesion glycolysis (TLG), tumor heterogeneity measured by histogram-based parameter skewness, and the majority of second-order or higher-order texture features were significantly associated with overall survival (OS) and/or recurrence-free survival (RFS). In multivariate analysis, age (P =.005), EBV DNA load (P = .0002), and uniformity (P = .001) independently predicted OS. Only skewness retained the independent prognostic significance for RFS. Tumor stage, standardized uptake value, or TLG did not show an independent association with survival endpoints. The combination of uniformity, EBV DNA load, and age resulted in a more reliable prognostic stratification (P < .001).Conclusions: Tumor heterogeneity is superior to traditional PET parameters for predicting outcomes in primary NPC. The combination of uniformity with EBV DNA load can improve prognostic stratification in this clinical entity.Level Of Evidence: 4 Laryngoscope, 127:E22-E28, 2017. [ABSTRACT FROM AUTHOR]

Background Frontonasal fistulas can lead to life-threatening intracranial infections. Our refinement of the myocutaneous anterolateral thigh (ALT) flap for treating these fistulas is described. Methods A retrospective review of the microsurgical treatment of frontonasal fistulas is presented. Demographics, etiologies, outcomes, and complications were evaluated. Results Ten myocutaneous ALT flaps were used to reconstruct frontonasal fistula. The mean follow-up was 35 ± 2.5 months. Nine fistulas were secondary to oncologic resections, and one was due to a traumatic origin. Complications included a recurrent abscess in 1 case (10%); there were no cases of cerebrospinal fluid (CSF) leak or flap loss. Preoperative intracranial infections were present in 7 cases, with 6 successfully resolving their infection after surgical intervention and flap obliteration of their fistulas. Conclusion Refinements in the myocutaneous ALT flap design have been illustrated to provide robust dead-space obliteration with vascularized muscle and reliable simultaneous scalp coverage in the treatment of frontonasal fistulas. © 2015 Wiley Periodicals, Inc. Head Neck 38: E552-E558, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC). Methods We retrospectively examined 1616 patients with oral cavity SCC who underwent radical surgery between 1996 and 2011. The study participants were classified into 2 subgroups according to the use of MDTC. Results Five-year outcomes were significantly better in the MDTC group than in the no-MDTC group (neck control, 88% vs 84%, p = .0397; disease-specific survival [DSS], 83% vs 78%, p = .0114; and overall survival [OS], 70% vs 64%, p = .0002, respectively). Among patients who were scheduled to undergo adjuvant therapy, the number who completed their adjuvant treatment was significantly higher in the MDTC group than in the no-MDTC group (90% vs 60% to 70%, p < .001). Conclusion The association of MDTC with improved outcomes may be potentially explained by a better therapeutic alliance between the patient and the tumor board, and/or a greater thoroughness in clinical management. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1544-E1553, 2016 [ABSTRACT FROM AUTHOR]

Background Vocal cord leukoplakia comprises a variety of lesions. The purpose of this study was to stratify vocal leukoplakias before surgery. Methods Patients with an initial diagnosis of vocal leukoplakia who underwent surgical excision at a tertiary referral center in Taiwan were recruited for this study. Their clinical records, including age, sex, preoperative laryngoscopic images in the office setting, and final pathology reports were collected and analyzed. Results Patient age ( p = .010), nonhomogenous lesion texture ( p = .001), and existence of hyperemia ( p = .014) were identified as independent factors predicting malignancy. A predictive formula was established accordingly. The model showed an excellent discrimination role by receiver operating characteristic curve analysis (area under the curve = 0.86; p < .001). Conclusion This study confirmed the value of a scoring system based on laryngoscopic characteristics and patient age for predicting the histologic results in vocal leukoplakia. It is helpful for classifying vocal leukoplakia and pretreatment planning. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1998-E2003, 2016 [ABSTRACT FROM AUTHOR]

Recent studies conducted in patients with chronic diseases have reported an inverse association between body mass index ( BMI) and mortality. However, the question as to whether BMI may predict prognosis in patients with metastatic cancer remains open. We therefore designed the current retrospective study to investigate the potential association between BMI and overall survival ( OS) in patients with distant metastases ( DM) and a favorable performance status. Between 2000 and 2012, a total of 4010 cancer patients with DM who required radiotherapy ( RT) and had their BMI measured at the initiation of RT were identified. The relation between BMI and OS was examined by univariate and multivariable analysis. The median OS time was 3.23 months (range: 0.1-122.17) for underweight patients, 6.08 months (range: 0.03-149.46) for normal-weight patients, 7.99 months (range: 0.07-158.01) for overweight patients, and 12.49 months (range, 0.2-164.1) for obese patients (log-rank: P < 0.001). Compared with normal-weight patients, both obese ( HR = 0.676; 95% P < 0.001) and overweight individuals ( HR = 0.84; P < 0.001) had a reduced risk of all-cause mortality in multivariable analysis. Conversely, underweight patients had a significantly higher risk of death from all causes ( HR = 1.41; P < 0.001). Overweight and obesity are independent predictors of better OS in metastatic patients with a good performance status. Increased BMI may play a role to identify metastatic patients with superior survival outcome and exhibit a potential to encourage aggressive management in those patients even with metastases. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Bone marrow stromal cell antigen 2 (BST2) was one of the proteins that were found to be related to tumor metastasis in our previous proteomic study. Now we examine its clinical role on the oral cavity squamous cell carcinoma (OSCC). Study Design Individual retrospective cohort study and basic research. Methods Immunohistochemical analysis, Western blotting, and quantitative real-time polymerase chain reaction were used to demonstrate the expression levels of BST2 on 159 OSCC tumors. RNA interference was utilized for cell migration and proliferation study in vitro. Results BST2 expression was significantly higher in OSCC cells of metastatic lymph nodes and primary tumor cells, compared to adjacent normal epithelia. Higher BST2 expression was associated with positive N stage, advanced overall stage, perineural invasion, and tumor depth ( P = .049, .015, .021, and .010, respectively). OSCC patients with higher BST2 expression had poorer prognosis for disease-specific and disease-free survival ( P = .009 and .001, respectively). Multivariate analyses also demonstrated that higher BST2 expression is an independent prognostic factor of disease-specific and disease-free survival ( P = .047 and .013, respectively). In vitro suppression of BST2 expression in OEC-M1 cells showed that BST2 contributes to tumor migration of OSCC cells. Conclusions The findings in this study indicate that BST2 expression in OSCC tumors is an independent prognostic factor of patient survival and associated with tumor metastasis. Level of Evidence NA Laryngoscope, 124:E354-E360, 2014 [ABSTRACT FROM AUTHOR]

BACKGROUND A previous comparative tissue proteomics study by the authors of the current study led to the identification of caldesmon (CaD) as one of the proteins associated with cervical metastasis of oral cavity squamous cell carcinoma (OSCC). In the current investigation, the authors focused on the potential functions of CaD in patients with OSCC. METHODS CaD expression was examined in tissue samples from 155 patients using immunohistochemical analysis. The expression of CaD variants was determined by Western blot analysis and reverse transcriptase-polymerase chain reaction. In addition, the specific effects of CaD gene overexpression and silence were determined in OSCC cell lines. RESULTS CaD expression was found to be significantly higher in tumor cells from metastatic lymph nodes compared with primary tumor cells, and was nearly absent in normal oral epithelia. Higher CaD expression was found to be correlated with positive N classification, poor differentiation, perineural invasion, and tumor depth ( P = .001, P = .029, P = .001, and P = .031, respectively). In survival analyses, OSCC patients with higher CaD expression were found to have poorer prognosis with regard to disease-specific survival and disease-free survival ( P = .003 and P = .014, respectively). Multivariate analyses further indicated that higher CaD expression was an independent predictor of disease-specific survival ( P = .043). Serum CaD levels were found to be significantly higher in patients with OSCC, but this finding was not associated with clinicopathological manifestations. Data obtained from in vitro suppression, rescue, and overexpression of CaD in OEC-M1 cells indicated that CaD promotes migration and invasive processes in OSCC cells. CONCLUSIONS The findings of the current study collectively suggest that the low-molecular-weight CaD expression in OSCC tumors is associated with tumor metastasis and patient survival. Cancer 2013;119:4003-4011. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

This article presents a study to determine the role of serum interleukin-6 concentration for oral cavity in case of squamous cell carcinomas. The study employed cohort analysis which employed 237 untreated patients, 104 individuals with oral premalignant lesions and 125 health individuals. The serum concentration was measured by the enzyme-linked immunosorbent assay. The study revealed that serum interleukin-6 level was associated with tumor.

Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 and NLRP3, respectively. In mice, tumour-derived IL-1β inhibits tumour growth and enhances survival through host responses. Mechanistically, IL-1β-mediated anti-tumour effects depend on infiltrated immunostimulatory neutrophils. We show further that presence of tumour-associated neutrophils is significantly associated with better survival in NPC patients. Thus, tumour inflammasomes play a key role in tumour control by recruiting neutrophils, and their expression levels are favourable prognostic markers and promising therapeutic targets in patients. [ABSTRACT FROM AUTHOR]

Hence, the events per variable (EPV) number was three (15 patients with occurrence of osteoradionecrosis [ORN] while examining five variables) instead of 0.9. A nomogram to predict osteoradionecrosis in oral cancer after marginal mandibulectomy and radiotherapy [published online February 20, 2019]. [Extracted from the article]

Background To investigate the pretreatment copy number and the clearance rate of plasma Epstein-Barr virus (EBV) DNA as novel prognostic outcome markers for metastatic nasopharyngeal carcinoma (NPC). Methods Seventy-three patients with metastatic NPC were treated at outpatient department. Plasma EBV DNA concentrations and half-life values of plasma viral clearance rates, were determined by real-time quantitative polymerase chain reaction. Results Treatment response evaluated after 3 to 6 months of treatment showed that the overall response rate was 53.5%. The pretreatment plasma EBV DNA concentrations and the half-life of plasma EBV DNA clearance rates had significant effects on treatment response and overall survival prediction. In the chemotherapy regimen, gemcitabine plus cisplatin had a better treatment outcome than the cisplatin plus oral UFT and calcium folinate-based regimens. Conclusions The pretreatment plasma EBV DNA copy number and their clearance rates are significant predictors for NPC treatment outcome. © 2011 Wiley Periodicals, Inc. Head Neck, 2012 [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous intracranial germinoma (IG) studies have investigated the effect of different radiotherapy (RT) volumes and the necessity for adjunctive chemotherapy, but there is currently no consensus on the best treatment for this tumor. METHODS: From January 1989 to December 2009, 80 IG patients (≤20 years old) were treated with various RT regimens. Of them, 14 patients had craniospinal irradiation (CSI) + primary boost (PB); 8 patients had whole-brain irradiation (WBI) + PB; 31 patients had whole ventricular irradiation (WVI) + PB; and 27 patients had focal RT only. Twenty-nine patients (36.2%) also received systemic chemotherapy (CHT). Survival was estimated by the Kaplan-Meier method and variables affecting survival were analyzed by the Cox proportional hazard model. RESULTS: Eleven patients (13.8%) developed local recurrence or dissemination after treatment, and 10 of these patients were in the focal RT group. The 5-year relapse-free survival (RFS) for the CSI, WBI, WVI, and focal RT patients were 100%, 85.7%, 100%, and 84.6%, respectively ( P = .001). The 5-year overall survival (OS) for CSI, WBI, WVI, and focal RT patients was 100%, 83.3%, 100%, and 87.9%, respectively ( P = .125). Focal irradiation ( P = .02) and initial use of CHT ( P = .021) were negatively associated with RFS. CONCLUSIONS: Focal RT plus CHT were associated with inferior control of IG and a higher incidence of CHT-related toxicities. Adjustment of the radiation volume to the whole ventricular system without CHT is sufficient for treatment of nondisseminated IGs, even with lower primary RT doses (<36 Gy). Cancer 2011. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This study evaluated associations between the histological differentiation of oral squamous cell carcinoma and additional clinicopathological manifestations, adverse events after treatment, and the outcomes of patients in a region prevalent for betel quid chewing. Study Design: Case series with chart review. Setting: Tertiary referral center. Subjects and Methods: A total of 150 patients with primary oral squamous cell carcinomas who underwent surgery with or without adjuvant therapy were enrolled. Results: Well, moderate, and poorly differentiated oral squamous cell carcinomas were reported in 54 (36%), 84 (56%), and 12 (8%) patients, respectively. There were no significant differences among different histological differentiations in age, sex, tumor, node, metastasis stage, bone invasion, depth of invasion, and history of carcinogen exposure. However, we found significant associations between tumor histological differentiation and nodal metastasis (P < 0.0001), extracapsular spread (P = 0.002), and perineural invasion (P < 0.0001). In the analysis of adverse events for survival during patient follow-up, oral squamous cell carcinomas with poor differentiation had a higher probability of developing neck recurrence (P = 0.001) and distant metastasis (P = 0.019), but not local recurrence or a second primary cancer. For survival analysis, univariate analysis showed that patient age, tumor stage, extracapsular spread, presence of perineural invasion, and tumor differentiation were significant factors. Multivariate analysis further demonstrated that poor differentiation (P = 0.007) was still a statistically significant factor. Conclusion: The current study demonstrates that poorer tumor histological classifications of oral squamous cell carcinoma are significantly associated with positive nodal status, extracapsular spread, perineural invasion of primary tumors, and the probability of developing neck recurrence and distant metastasis after treatment. [Copyright &y& Elsevier]

Objectives: The objective of this study was to determine the characteristics of medially originated inverted papilloma (MOIP) and compare them with laterally originated inverted papilloma (LOIP). Methods: A retrospective review of the charts for a total of 83 patients with sinonasal inverted papilloma (IP) was conducted. Tumors originating from the nasal septum or the turbinates were categorized as MOIP, whereas tumors originating from the four sinuses were categorized as LOIP. Results: Twenty-eight (34%) and 55 (66%) cases were categorized as MOIP and LOIP. MOIP from the middle turbinate behaved more aggressively than LOIP from the ethmoid sinus (P = 0.009), but less aggressively than LOIP from the maxillary medial wall (P < 0.05). Radical procedures were implemented in 14 patients with LOIP, but not in any patients with MOIP (P = 0.002). The recurrence rates were comparable in both groups (P = 0.472). Conclusions: The categorization of IP on the basis of tumor origin enabled a better surgical design and more accurate excision of the tumor. Although in some cases MOIP may behave more aggressively, radical procedures were indicated in only the late Krouse stage LOIP without compromising the recurrence rate. [Copyright &y& Elsevier]

Objective: To evaluate the difference in anatomical and invasive characteristics of primary and secondary paranasal sinus mucoceles. Study Design: A retrospective chart review at a tertiary academic center. Results: During a 10-year period, 57 and 109 patients with primary and secondary mucoceles were enrolled, respectively. Thirty-five (61.4%) of primary and 26 (23.9%) of secondary mucoceles had intraorbital extension (IOE), while seven (12.3%) of primary and two (1.8%) of secondary mucoceles had intracranial extension (ICE). In comparison of tendency for IOE or ICE between primary and secondary mucoceles in each sinus, only primary maxillary mucoceles were shown to have a significantly higher probability of IOE than secondary maxillary mucoceles. Among primary mucoceles, ethmoid mucoceles had a significantly greater capability to cause IOE while maxillary mucoceles had the least. Among secondary mucoceles, frontal and ethmoid mucoceles had a greater ability to cause IOE while maxillary mucoceles had the least. As for ICE, sphenoid mucoceles had a greater potential in both groups. Conclusions: Primary mucoceles seem to have a greater potential to cause IOE and ICE than secondary mucoceles. In both groups, ethmoid mucoceles have a higher potential of IOE, while sphenoid mucoceles have a greater tendency to cause ICE. [Copyright &y& Elsevier]

Background. The C-terminal activation region 2 (CTAR2) of Epstein-Barr virus latent membrane protein 1 is the major site that correlates with metastasis-related signaling pathway. The variation of CTAR2 sequence may affect the incidence of distant metastasis in patients with nasopharyngeal carcinoma (NPC). Methods. Two hundred forty-nine specimens from consecutive patients with nonmetastatic NPC were collected. Amplification by polymerase chain reaction and sequence analysis of CTAR2 were performed. DNA sequence identical to the Cao strain was grouped as Cao CTAR2, whereas sequences differing from Cao made up non-Cao CTAR2. Clinical characteristics and CTAR2 status were subjected to statistical analysis for distant metastasis. Results. Non-Cao CTAR2 was associated with a statistically significant lower distance metastasis and superior survival rate. A combination of clinical stage and CTAR2 expression provided an accurate method of identifying high risk of metastasis. Conclusion. NPC patients with non-Cao CTAR2 were less likely to have metastasis develop than those characterized by Cao CTAR2. © 2006 Wiley Periodicals, Inc. Head Neck 2007 [ABSTRACT FROM AUTHOR]

Background. Composite maxillary defects often involve the maxilla, nasal mucosa, palate, and maxillary sinus. We presented the surgical techniques and outcome of the osteomyocutaneous peroneal artery perforator (PAP) flap for reconstruction of composite maxillary defects. Methods. Six patients underwent an osteomyocutaneous PAP flap reconstruction of composite maxillary defects. The average age was 52 years. The defects were Cordeiro type II in three patients and type IV midfacial defects in another three patients. Results. No total or partial flap failures occurred. At a mean 12-month follow-up, five patients had a normal speech and were able to eat a regular diet. One patient tolerated a soft diet and had intelligible speech. One patient had ectropion develop. Excellent cosmesis was found in five patients. Conclusions. The osteomyocutaneous PAP flap represents a further refinement of the fibula flap and increases its versatility, with multiple skin paddles, bone segments, and soleus muscle independently isolated. It is a comparable reconstruction option for composite maxillary defects. © 2005 Wiley Periodicals, Inc. Head Neck28: 297–304, 2006 [ABSTRACT FROM AUTHOR]

Background. Atypical carcinoid tumor is a neuroendocrine tumor; its occurrence in the larynx is uncommon, and clinical manifestations are rare. We report an unusual case of atypical carcinoid tumor of the epiglottis mimicking a supraglottic retention cyst. Methods. A 44-year-old woman complained of an intermittent globus sensation of the throat of 2 years' duration. A 1.0- × 0.8-cm cystic lesion was found over the tip of the epiglottis. A supraglottic retention cyst was initially diagnosed, and the patient was treated medically. Her symptoms persisted, so we performed a laryngoscopic biopsy, which suggested an atypical carcinoid tumor. Results. Transoral endoscopic CO2 laser surgery and bilateral elective neck dissection were subsequently performed. The 2-year follow-up did not reveal any locoregional recurrence or distant metastasis. Conclusions. This aggressive neoplasm may cause only a few, unremarkable symptoms and masquerade as a supraglottic cyst. Endoscopic CO2 laser surgery can be used to resect this uncommon tumor, with oncologically sound results and without surgical morbidity. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005 [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of ultrasound-guided percutaneous closed drainage in the management of abscesses in the head and neck. Study Design: Prospective, controlled study. Methods: From January 1998 to December 1999, patients presenting with a unilocular abscess in the head and neck and who subsequently underwent echo-guided percutaneous drainage were enrolled in the study. Results: Fourteen patients were enrolled in the study. No patients needed open surgical drainage afterward. By our protocol, only 8 patients had an indwelling catheter. After treatment, all patients were cured of their disease completely without any complication. Conclusions: Ultrasound-guided percutaneous closed drainage is a safe and effective procedure and might be most beneficial in well-defined and/or unilocular abscess in the head and neck. Closed drainage could be tried initially in an abscess of the deeper visceral spaces and will not impede any subsequent intervention by surgery. Hospital stay can be shortened and potential surgical complications may be avoided by using this procedure. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the feasibility of molecular diagnosis of nasopharyngeal carcinoma (NPC) by combining nasopharyngeal swab and polymerase chain reaction (PCR) to detect Epstein-Barr virus (EBV) derived latent membrane protein-1 gene (LMP-1) and Epstein-Barr nuclear antigen gene (EBNA).Methods: 437 adults underwent nasopharyngoscopy, possible biopsy, and nasopharyngeal swab to obtain nasopharyngeal cells for the detection of LMP-1 and EBNA by PCR.Results: By detecting LMP-1 and EBNA in the nasopharyngeal swabs, NPC could be diagnosed with a false-positive rate of 1.7% (6/354), a false-negative rate of 8.6% (6/70), a sensitivity of 91.4% (64/70), a specificity of 98.3% (348/354), positive predictive value of 91.4% (64/70), and negative predictive value of 98.3% (348/354).Conclusion: Detecting EBV genomic LMP-1 and EBNA by nasopharyngeal swab verifies NPC with a sensitivity of 91.4% and specificity of 98.3%. The nasopharyngeal swab coupled with PCR based EBV LMP-1 and EBNA detection could serve as a good supplement to pathological diagnosis of NPC. [ABSTRACT FROM AUTHOR]

Objectives: Epstein-Barr virus (EBV) is closely related to nasopharyngeal carcinoma (NPC). Detection of EBV genomic DNA in a nasopharyngeal swab specimen may indicate the presence of NPC, and the EBV genomic DNA is only detected in patients with NPC and not in other head and neck cancers. This study aims to prove that detection of EBV genomic DNA by means of the latent membrane protein (LMP)-1 gene and the Epstein-Barr nuclear antigen (EBNA)-1 gene in the nasopharynx in NPC patients after radiation therapy indicates local recurrence of NPC.Study Design: Prospective.Methods: Nasopharyngeal swab with polymerase chain reaction (PCR)-based LMP-1 and EBNA-1 gene detection was used to monitor local recurrence in 84 NPC patients who completed radiation therapy.Results: Of the 12 patients demonstrating positive LMP-1 and EBNA-1 gene, 11 had local recurrence, and 10 of them had early rT1 mucosal recurrence. Subsequent salvage nasopharyngectomy controlled local disease in nine. Only one local recurrence in the skull base failed to show LMP-1 gene initially. Detection of LMP-1 gene and later verification with EBNA-1 gene from nasopharyngeal swabs in NPC patients after radiation therapy predicted local recurrence with a sensitivity of 91.7% and a specificity of 98.6%.Conclusions: Nasopharyngeal swab with LMP-1 and EBNA-1 gene detection is a useful and reliable method to monitor local recurrence in NPC patients. It helps to detect recurrence early and may improve local control and enhance survival. [ABSTRACT FROM AUTHOR]