Oral And Oropharyngeal Squamous Cell Carcinoma Research Articles

THE IMPACT OF ORAL AND OROPHARYNGEAL CANCER PATIENT'S MEDICAL PROFILE ON TREATMENT-RELATED TOXICITIES.

Objective To characterize oral and oropharyngeal squamous cell carcinoma (OOPSCC) patients with dental needs before cancer treatment. Patient's pre-oncological treatment data, including medical and sociodemographic characteristics, and laboratory tests results, were correlated with treatment-related head and neck toxicities. Study Design A prospective cohort study. Results 110 patients were included. The most common comorbidities were hypertension, dyslipidemia, and diabetes. C-reactive protein, hemoglobin, and hematocrit were the most altered tests results. Toxicities were progressive over time. There was a positive correlation (0.268) between the number of medications and oral mucositis (OM), and a negative correlation (-0.257) between medications and dysgeusia. For OM, altered exams showed significative P-values: thyroxine (T4) and free thyroxine (FT4) starting at D15; calcium at D5/10/30; urea at D25/30/33-35; creatinine at D15/30; alkaline phosphatase at D20/25; syphilis at D15/30. Family income and housing were OM predictors. Oral candidiasis (OC) was associated with syphilis and HIV at D20. Conclusion OOPSCC patients have several comorbidities and abnormal laboratory results. No dental treatment before cancer treatment resulted in adverse events. Laboratory findings of altered T4, FT4, urea, calcium, alkaline phosphatase, creatinine, and syphilis may be useful predictors of OM. Syphilis and HIV may also be predictors of OC secondary to OOPSCC treatment. To characterize oral and oropharyngeal squamous cell carcinoma (OOPSCC) patients with dental needs before cancer treatment. Patient's pre-oncological treatment data, including medical and sociodemographic characteristics, and laboratory tests results, were correlated with treatment-related head and neck toxicities. A prospective cohort study. 110 patients were included. The most common comorbidities were hypertension, dyslipidemia, and diabetes. C-reactive protein, hemoglobin, and hematocrit were the most altered tests results. Toxicities were progressive over time. There was a positive correlation (0.268) between the number of medications and oral mucositis (OM), and a negative correlation (-0.257) between medications and dysgeusia. For OM, altered exams showed significative P-values: thyroxine (T4) and free thyroxine (FT4) starting at D15; calcium at D5/10/30; urea at D25/30/33-35; creatinine at D15/30; alkaline phosphatase at D20/25; syphilis at D15/30. Family income and housing were OM predictors. Oral candidiasis (OC) was associated with syphilis and HIV at D20. OOPSCC patients have several comorbidities and abnormal laboratory results. No dental treatment before cancer treatment resulted in adverse events. Laboratory findings of altered T4, FT4, urea, calcium, alkaline phosphatase, creatinine, and syphilis may be useful predictors of OM. Syphilis and HIV may also be predictors of OC secondary to OOPSCC treatment.

Outcomes of Oral and Oropharyngeal Squamous Cell Carcinoma Related to Healthcare Coverage: A Retrospective Cohort Study in Brazil

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.

Regulatory Mechanisms of Endogenous APOBEC3B Expression in HPV(+) and (–) Oral Premalignancies and Head and Neck Cancer

<h3>Introduction</h3> HPV(+) oral and oropharyngeal squamous cell carcinoma (OOPSCC) shows strong association with high-risk HPV16 and 18. The DNA cytosine deaminase APOBEC3B constitutes a major endogenous source of muta- tions in a wide variety of cancers. APOBEC3B causes C-to-T/-G base substitutions in 5'-TCA/T trinucleotide motifs and is overexpressed in head and neck cancer (HNC). High-risk HPV infection and dysregulation of the RB/E2F axis regu- late <i>APOBEC3B in vitro</i>. Here, we investigate changes of APOBEC3B levels in HPV(+) and (–) oral epithelial dysplasia (OED) and OOPSCC, and probe whether APOBEC3B upregulation correlates with cellular proliferation. <h3>Materials and Methods</h3> APOBEC3B and Ki67 expression was assessed by immunohistochemistry in HPV(+) OED (n=10) and OOPSCC (n=28), and HPV(–) low-grade (n=42) and high-grade OED (n=38), and OSCC (n=46). Epithelial hyperplasia (OEH, n=14) and normal adjacent epithelium (n=10) served as controls. APOBEC3B H-scores and per- centage of Ki67(+) cells were calculated using the Aperio ScanScope XT platform. Public NGS datasets available through TCGA were mined to identify molecular mechanisms associated with APOBEC3B upregulation in HNC. <h3>Results</h3> High-risk HPV significantly upregulated APOBEC3B in OED (Kruskal-Wallis test, p<0.05) and OOPSCC (p<0.01) compared to OEH. HPV(+) OEDs and tumors showed strong and diffuse, nuclear APOBEC3B immunore- activity which mirrored p16 staining and coincided with disrupted p53 expression. Progressive APOBEC3B up- regulation was observed in HPV(–) lesions; high-grade premalignancies and OSCCs showed significantly elevated APOBEC3B H-scores compared to low-grade OED (p<0.01) and controls (p<0.01). High mRNA and protein APOBEC3B levels strongly associated with advanced histologic grading in HPV(–) OSCC (p<0.01). A positive linear correlation was evident between APOBEC3B and Ki67 expression (Pearson's r=0.5), while RNAseq analysis suggests cell cycle regulation of APOBEC3B in HPV(–) HNC. <h3>Conclusions</h3> High-risk HPV drives upregulation of APOBEC3B in viral-related OED and HNC. In non-viral lesions, APOBEC3B levels also increase in a mechanism associated in part with cellular proliferation.

Are Survival Outcomes Different for Young and Old Patients with Oral and Oropharyngeal Squamous Cell Carcinoma? A Systematic Review and Meta-Analysis.

Simple SummaryOral cancer was considered a disease of old age. However, there has been a recent surge in the incidence of oral cancer in young individuals. Age dependence on survival outcomes such as overall survival, disease-free survival, recurrence, distant metastasis and second primary in surgically treated oral cancer has been investigated several times and the results differ. This systematic review and meta-analysis has been conducted to address this concern. The results of the present research may facilitate age-dependent prognosis stratification, which would assist in treatment planning in oral cancer patients.This systematic review and meta-analysis aims to address whether age can be a determinant of overall survival (OS), disease-free survival (DFS), recurrence, distant metastasis (DM) and second primary (SP) in surgically treated oral and oropharyngeal squamous cell carcinoma (OOPSCC). A total of 4981 cases and 44254 controls from 25 comparative observational studies were included in the analysis. A significantly better OS (matched subgroup analysis: OR 1.64; 95% CI 1.31–2.04, overall analysis: OR 1.48; 95% CI 1.09–2.01) was observed in young patients compared to older adults, with heterogeneity ranging from moderate to severe. Worse DFS (unmatched subgroup analysis OR 0.43; 95% CI 0.27–0.68) was observed in young patients compared to older adults with minimal to moderate heterogeneity. The frequency of recurrence (OR 1.49; 95% CI 1.10–2.02) and DM (OR 1.83; 95% CI 1.10–3.03) was significantly higher in the young patients, as found in unmatched and matched subgroup analysis, with the least heterogeneities. Young age can be considered as an independent prognostic factor for recurrence and distant metastases in OOP-SCC. Larger and methodologically robust observational studies with longer follow-up are needed to establish the definitive role of age as an independent prognostic factor on OS and DFS in OOPSCC.

Developing a predictive risk score for perioperative blood transfusion: a retrospective study in patients with oral and oropharyngeal squamous cell carcinoma undergoing free flap reconstruction surgery.

BackgroundA simple and accurate scoring system to predict risk of blood transfusion in patients having surgical tumor resection with immediate free flap reconstruction primary surgery for oral and oropharyngeal squamous cell carcinoma (OOSCC) is lacking. Anticipating the blood transfusion requirements in patients with oral cancer is of great clinical importance. This research aimed to propose a valid model to predict transfusion requirements in patients undergoing surgery with free flap reconstruction for an OOSCC.MethodsThis retrospective study consisted of 385 patients who underwent oncologic surgery with immediate free flap reconstruction for locally advanced OOSCC from 2012 to 2019. The primary outcome measured was the exposure of patients to perioperative allogeneic blood transfusion. Based on a multivariate model of independent risk variables and their odds ratio, a blood transfusion risk score (TRS) was developed to predict the likelihood of the perioperative blood transfusion. The discriminatory accuracy of the model was evaluated using the area under the receiver operating characteristic (ROC) curve, and Youden index was used to identify the optimal cut-point.ResultsLogistic regression analyses identified lymph node status, preoperative hemoglobin (Hb) levels, bone resection, osseous free tissue transfer, and operative duration were identified as independent predictors of blood transfusion. A TRS integrating these variables was separated into three categories. The TRS assessed the transfusion risk with good predictive ability, with an overall area under the ROC curve (AUC) was 0.826. At the optimal cut-point of 5.5, the TRS had a sensitivity of 72.3% and a specificity of 78.2%. The ROC analysis showed that patients with a TRS of 5.5 or more had a greater requirement for perioperative transfusion.ConclusionsThe use of the integer-based TRS allowed the identification of high-risk patients who may require perioperative transfusion undergoing tumor resection surgery for the treatment of OOSCC.

Association of PON1, TNF-α and TGF-β gene polymorphisms with prognosis in oral and oropharyngeal squamous cell carcinoma

Objective The oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for 90–95% of tumours in the oral cavity. Single nucleotide polymorphism (SNP) in the coding region of PON1, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) have been associated with to development of different cancers. Our aim was to investigate the prognostic value of PON1 (rs854560 and rs662), TNF-α (rs1800629 and rs361525) and TGF-β (rs1800469) SNPs in OOSCC. Materials and methods We genotyped 163 OOSCC patients and 146 patients from group of control for PON1 (rs854560 and rs662), TNF-α (rs1800629 and rs361525) and TGF-β (rs1800469) SNPs by real-time polymerase chain reaction (PCR). Results TNF-α (rs1800629) GG genotype was significantly more frequent in intraoral lesions and clinical stages III and IV, while the polymorphic AA genotype in lip lesion and clinical stages I and II. Moreover, TGF-β (rs1800469) AG and AA genotypes were significantly more frequent in larger tumours (T3 e T4). TNF-α (rs1800629) AG genotype had poor survival and patients carrying the PON1 (rs662) TT genotype tended to poor survival. Conclusions Results suggest that the rs1800629 and rs1800469 could exert influence in the more aggressive behaviour of OOSCC and the genotypes AG of rs1800629, and TT of rs662 could be markers with prognostic value in OOSCC.

ASSOCIATION OF PON1, TNFα, AND TGFβ GENE POLYMORPHISMS WITH PROGNOSIS IN ORAL AND OROPHARYNGEAL SQUAMOUS CELL CARCINOMA

The oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for 90% to 95% of tumors in the oral cavity. Single nucleotide polymorphism (SNP) in the coding region of PON1, TNFα, and TGFβ have been associated with the development of different cancers. Objective: Investigate the prognostic value of PON1 (rs854560 and rs662), TNFα (rs1800629 and rs361525), and TGFβ (rs1800469) SNPs in OOSCC. Study Design: One hundred sixty-three patients with OOSCC were genotyped along with 146 control patients for PON1 (rs854560 and rs662); TNFα (rs1800629 and rs361525); and TGFβ (rs1800469) SNPs by real-time polymerase chain reaction. Results: TNFα (rs1800629) GG genotype was significantly more frequent in intraoral lesions and clinical stages III and IV, while the polymorphic AA genotype was found predominantly in lip lesions and clinical stages I and II. Moreover, TGFβ (rs1800469) AG and AA genotypes were significantly more frequent in larger tumors (T3 e T4). The TNFα (rs1800629) AG genotype was associated with poor survival and patients carrying the PON1 (rs662) TT genotype also had a tendency for poor survival. CONCLUSIONS: The results suggest that the rs1800629 and rs1800469 variations could exert influence on the more aggressive behavior of OOSCC, and the genotypes AG of rs1800629 and TT of rs662 could be markers with prognostic value in OOSCC. The oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for 90% to 95% of tumors in the oral cavity. Single nucleotide polymorphism (SNP) in the coding region of PON1, TNFα, and TGFβ have been associated with the development of different cancers. Objective: Investigate the prognostic value of PON1 (rs854560 and rs662), TNFα (rs1800629 and rs361525), and TGFβ (rs1800469) SNPs in OOSCC. Study Design: One hundred sixty-three patients with OOSCC were genotyped along with 146 control patients for PON1 (rs854560 and rs662); TNFα (rs1800629 and rs361525); and TGFβ (rs1800469) SNPs by real-time polymerase chain reaction. Results: TNFα (rs1800629) GG genotype was significantly more frequent in intraoral lesions and clinical stages III and IV, while the polymorphic AA genotype was found predominantly in lip lesions and clinical stages I and II. Moreover, TGFβ (rs1800469) AG and AA genotypes were significantly more frequent in larger tumors (T3 e T4). The TNFα (rs1800629) AG genotype was associated with poor survival and patients carrying the PON1 (rs662) TT genotype also had a tendency for poor survival. CONCLUSIONS: The results suggest that the rs1800629 and rs1800469 variations could exert influence on the more aggressive behavior of OOSCC, and the genotypes AG of rs1800629 and TT of rs662 could be markers with prognostic value in OOSCC.

CD44 and associated markers in oral rinses and tissues from oral and oropharyngeal cancer patients

Oral and oropharyngeal squamous cell carcinoma (OOPSCC) is a debilitating disease. Salivary rinses contain soluble tumor markers including CD44 (solCD44) and total protein (TP) that may aid detection and prognosis of these aggressive tumors. Here we aim to examine the relationship between these salivary biomarkers and tissue markers p16 and CD44 and determine whether these markers can predict progression-free survival (PFS) and overall survival (OS). Prospective study to update biomarkers using oral rinses and tissues from OOPSC patients enrolled between 2007 and 2012 at an academic tertiary referral center. 64 cases from a 300-subject case-control study with archived tissue for immunohistochemistry were included. 82.8% were male, 84.4% were ever smokers, 70.3% had disease stage T3-T4, and 57.8% presented with nodal disease. Nineteen patients (25%) were p16 positive. The group with strong tissue CD44 expression in membrane and cytoplasm had higher levels of solCD44 (mean 10.73ng/ml) than other groups (5.47ng/ml) (p=0.033). TP levels were significantly reduced in oral rinses from subjects with p16 universal gross tumor tissue staining (mean 0.80 vs. 1.08mg/ml; p=0.039). On multivariate analysis, universal CD44 gross tissue staining and TP levels≥1 mg/ml demonstrated poorer PFS, with the latter also affecting OS. Poorer survival was associated with soluble CD44≥5.33 ng/ml and TP≥1 mg/ml. Direct associations were found between high solCD44 levels and strong membrane and cytoplasmic CD44 expression, and between high TP levels and peripheral/mixed p16 gross staining. Poorer PFS and OS are significantly associated with higher levels of solCD44 and protein in oral rinses.

Tumor heterogeneity in oral and oropharyngeal squamous cell carcinoma assessed by texture analysis of CT and conventional MRI: a potential marker of overall survival.

BackgroundThe combined prognostic value of texture analysis on computed tomography (CT) and conventional magnetic resonance imaging (MRI) in oral and oropharyngeal squamous cell carcinoma (OOSCC) h...

Clinicopathological features, management and outcome of patients with poorly-differentiated oral and oropharyngeal squamous cell carcinoma

BackgroundThe purpose of this study was to explore the clinicopathological features, risk factors, and management of poorly differentiated oral and oropharyngeal squamous cell carcinoma (OOSCC) patients in the northern Chinese population. MethodA total of 118 poorly differentiated OOSCC patients from 2236 consecutive cases were retrospectively enrolled in this study. ResultsCox regression analysis showed that site (hazard ratio (HR): 2.561, 95% confidence interval (CI): 1.064–6.164, p = 0.036) and lymph node ratio (LNR) (HR: 3.915, 95% CI: 1.797–8.530, p = 0.001) were independent predictive factors for 5-year disease-specific survival (DSS). LNR >0.036, oropharynx site, and advanced clinical stage formulate a model of risk stratification. The patients with a risk score of ≥2 were identified as the high-risk population, and patients with a risk score of 0 or 1 were identified as the low-risk population. Patients in the high-risk population who underwent surgery plus concurrent chemoradiotherapy (CCRT) had markedly better 5-year DSS than those who only underwent surgery (60.0% vs. 20.0%, p = 0.016). However, patients in the low-risk population who underwent surgery alone exhibited a similar 5-year DSS (68.2%) compared with those who received surgery plus radiotherapy (RT) (68.2%) or surgery plus CCRT (50.0%) (p = 0.907). ConclusionsHigh LNR, oropharynx site and advanced clinical stage constitute a model of risk stratification for patients with poorly differentiated OOSCC. If two or more risk factors are present, surgery and adjuvant chemoradiotherapy can give the best prognosis.

Prevalence of EGFR Tyrosine Kinase Domain Mutations in Head and Neck Squamous Cell Carcinoma: Cohort Study and Systematic Review.

Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain (TKD) are associated with response and resistance to targeted therapy. The EGFR mutation status in patients with advanced oral and oropharyngeal squamous cell carcinoma (OOSCC) was evaluated. A systematic literature review was undertaken to summarize current evidence and estimate the overall prevalence of EGFR TKD mutations in patients with head and neck squamous cell carcinoma (HNSCC). Genomic DNA was extracted from formalin-fixed, paraffin-embedded tumor samples of 113 patients with OOSCC. Pyrosequencing was performed to investigate mutations in EGFR exons 18 to 21. Medline databases were searched for relevant studies. Studies reporting mutations in the EGFR TKD in HNSCC were eligible for inclusion in the systematic review. No mutations in the EGFR TKD were observed in 113 samples of OOSCC. A total of 53 eligible studies were included in the systematic review. In total, from the review, 117 patients harboring a total of 159 EGFR TKD mutations were reported among 4122 patients with HNSCC. The overall prevalence of EGFR TKD mutations in HNSCC was 2.8%. Large-scale studies are warranted to provide further evidence regarding the mutation status of EGFR in patients with HNSCC.

Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer

BackgroundWe aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC).MethodsA cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan–Meier curves were used for survival analyses.ResultsSeventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09–2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11–2.86, p = 0.016).ConclusionElevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC.

Identification of methylation markers for the prediction of nodal metastasis in oral and oropharyngeal squamous cell carcinoma

Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed.

Sentinel Lymph Node Biopsy in Oral and Oropharyngeal Squamous Cell Carcinoma: Statistical Validation and Impact of Micrometastasis Involvement on the Neck Dissection Decision

To evaluate the effectiveness of sentinel lymph node biopsy (SLNB) as an optimal staging method in oral and oropharyngeal squamous cell carcinoma (OOSCC) and the impact of the extent of SLN involvement on the decision for neck dissection (ND). A prospective cohort study was performed in 96 consecutive patients with stage T1 to T4N0M0 OOSCC (mean follow-up, 62.9 months). SLN localization was determined using cervical lymphoscintigraphy and single-photon emission computed tomography. Patients underwent SLNB examination and ND. The ND specimen was investigated by hematoxylin and eosin (H&E) staining and the SLNs were investigated using H&E staining and step-serial sectioning and cytokeratin antibodies AE1 and AE3. The statistical study calculated the sensitivity and negative predictive value (NPV). The sample size of 96 patients was calculated for a 95% confidence interval with an accuracy of ±2% and an estimated a priori sensitivity of 99% compared with the benchmark. The impact of extent of SLN involvement on the decision for ND was analyzed by χ(2) test. A logistic regression model was used to assess the association of predictor variables with SLN involvement and neck disease. The diagnostic accuracy, sensitivity, NPV, and negative likelihood ratio were 95%, 88%, 94%, and 0.06. The statistical comparison between the extent of metastatic involvement of the SLN and neck disease was important for SLN macrometastasis (odds ratio = 11.9), but not for SLN micrometastasis (odds ratio = 0.93). SLNB examination is an excellent staging method in OOSCC. The present data indicate a very small risk of additional lymph node metastasis with SLN micrometastasis.

High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma – 5-year follow up of a population-based study

Conclusion: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. Objectives: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. Methods: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000–2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. Results: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.

Polymorphisms in NAT2 and GSTP1 are associated with survival in oral and oropharyngeal cancer

Introduction: Functional polymorphisms in drug metabolizing enzymes (DMEs) may be determinants of survival in oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods: OOSCC cases (N=159) with a history of either tobacco or alcohol use were genotyped for polymorphisms in eight DMEs. Overall and disease-specific survival were analyzed using Kaplan–Meier plots and the log-rank test. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) in exploratory analyses of patient subgroups. Results: Kaplan–Meier analyses showed N-acteyltransferase-2 (NAT2) fast acetylators experienced a 19.7% higher 5-year survival rate than slow acetylators (P=0.03) and this association was similar in oropharyngeal and oral cancer. After multiple adjustment, including tumor site and stage, the NAT2 fast acetylator phenotype was associated with improved overall survival (vs. slow acetylators) provided chemotherapy or radiation were not used (HR, 0.26; 95% CI, 0.10–0.66). However, NAT2 phenotype was unrelated to survival in patients treated with chemoradiotherapy (HR, 1.21; 95% CI, 0.54–2.73) or radiotherapy (HR, 0.67; 95% CI, 0.31–1.59) (P-for-NAT2/treatment-interaction=0.04). Normal activity GSTP1 was associated with a 19.2% reduction in 5-year disease-specific survival relative to reduced activity GSTP1 (P=0.04) but this association was not modified by treatment. Conclusions: Our results suggest that functional polymorphisms in NAT2 and GSTP1 are associated with OOSCC survival. Confirmation of these results in larger studies is required.

Survival of patients with pathologic T0N+ oral and oropharyngeal cancer after neoadjuvant therapy and surgery: the minority report

Treatment outcome of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) achieving complete pathologic response at the primary site (ypT0) but incomplete response in loco-regional lymph nodes after preoperative chemoradiation (ypN+) is poorly described in the literature. This study's objective was to assess the survival of patients with OOSCC with ypT0N+ disease. 176 patients with primary locally advanced OOSCC undergoing preoperative chemoradiotherapy were stratified according to the pathologic TNM classification into 6 groups: ypT0N0M0 (46%), ypT0N+M0 (10%), ypTNM I (24%), ypTNM II (4%), ypTNM III (6%), and ypTNM IV (10%). Three-year overall survival (OS) and recurrence-free survival (RFS) rates for the ypT0N+M0 group were both 61.8% and were similar to those of the ypTNM I group (OS 62.4%; RFS rate of 59.2%). Survival analyses showed that patients with OOSCC with ypT0N+ disease have a similar prognosis to those with pathologic TNM stage I.

HCRP1 expression status is a significant prognostic marker in oral and oropharyngeal cancer

The hepatocellular carcinoma-related protein 1 (HCRP1) 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). HCRP1 expression was determined by immunohistochemistry on tissue biopsy sections of 111 patients with locally advanced OOSCC undergoing neoadjuvant chemoradiotherapy followed by surgery. The Kaplan-Meier method and Cox regression models were used for survival analyses. 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). Low HCRP1 expression was found to be of adverse prognostic significance in patients with OOSCC who received preoperative chemoradiotherapy.

Failure in Oral or Oropharyngeal Cancer with Single‐Node Metastasis

Objective: 1) Analyze the oncologic results and related clinicopathologic factors of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) who presented as clinically single lymph node metastasis, nd underwent surgery. 2) To find out a rationale for optimal management in these selected cases. Method: Study design: Retrospective. Year study conducted: 10 years. Disease studied: Oral or oral cavity carcinoma with clinically single lymph node metastasis. Subjects: 54 patients. Setting: Tertiary center. Outcome measurement: Patterns of treatment failure, related clinicopathologic factors. Results: There was no metastasis in level V as clinical presentation, and only 1 case showed occult metastasis. Among the 15 cases (28%) of treatment failure, recurrence of lymph node metastasis was identified in only 1 case (1.9%). The most common cause of treatment failure or death was distant metastasis, which occurred in 10 patients (18.5%). Clinical ( P = .005) and pathologic ( P = .003) T stage were risk factors for the distant metastasis. Conclusion: Nodal recurrence was rare, and distant metastasis was the main cause of failure and death with OOPSCC with single lymph node metastasis. While there is feasibility to save level V in these cases, distant metastasis should be considered in adjuvant therapy and follow up for patients with advanced T stage.

Performance of 18F-FDG PET/contrast-enhanced CT in the staging of squamous cell carcinoma of the oral cavity and oropharynx

The aim of this study was to assess the diagnostic value of integrated whole body positron emission tomography/contrast-enhanced CT (PET/CECT) as a one step examination in the initial staging of oral and oropharyngeal squamous cell carcinoma (OOSCC). Seventy three consecutive OOSCC patients who underwent PET/CECT for initial staging and tumour resection and neck dissection as primary treatment, were included. For each PET/CECT result, the contribution of fluorine-18 fluorodeoxyglucose ( 18F-FDG)-uptake and radiologic criteria was assessed. PET/CECT results were correlated to histological specimens obtained with tumour resection and neck dissection. For detecting the primary tumour PET/CECT showed a sensitivity of 96% and for detecting cervical metastases a sensitivity and specificity of 89% and 81%, respectively. In the clinically N0 subgroup ( n = 37), PET/CECT showed a sensitivity and specificity of 64% and 81%, respectively. In five of six patients PET/CECT detected a second primary tumour. The results show that the use of diagnostic PET/CECT as a one step examination is a reliable alternative for PET/CT in combination with a separate diagnostic CT in patients with OOSC for initial staging. The need for treatment of the neck in the clinically negative neck should not be based on PET/CECT results only, due to the risk of missing a small metastasis.