ABSTRACT
OBJECTIVES: To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of pathologically confirmed HPSCC patients who had definitive radiation between January 2020 and January 2022 at Fudan University Eye and ENT Hospital. The routine blood results of patients were obtained to determine if the baseline ALC was connected with the response to radiation. The receiver operator characteristic (ROC) curve and LASSO-based Cox regression were employed to assess the predictive value of ALC for the efficacy of radiotherapy (RT). MAIN OUTCOME MEASURES AND RESULTS: RT induced a considerable drop in ALC and the level of ALC did not revert to the baseline values 1 year after radiation. The baseline level of ALC was higher in patients who met complete response after RT. The baseline ALC and monocyte counts demonstrated the predictive value of radiation effectiveness and ALC was an independent predictor. CONCLUSION: In HPSCC, lymphocytes were sensitive to radiation and reduced significantly during RT. The baseline ALC might be regarded as a predictive indicator of the effectiveness of RT.
Subject(s)
Hypopharyngeal Neoplasms , Humans , Male , Lymphocyte Count , Retrospective Studies , Female , Hypopharyngeal Neoplasms/radiotherapy , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/pathology , Middle Aged , Aged , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Squamous Cell Carcinoma of Head and Neck/blood , Squamous Cell Carcinoma of Head and Neck/pathology , Treatment Outcome , Predictive Value of Tests , Adult , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/pathology , ROC CurveABSTRACT
Actin-binding proteins (ABPs) and various signaling systems are involved in the process of squamous cell carcinoma of the larynx and hypopharynx (SCCLH) metastasis. The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA levels of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAI1 and RND3 and SCCLH metastasis. The serum levels of the above ABPs were estimated and the relationship between them and their mRNA expressions was analyzed. The expression levels of ABP mRNAs were measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T1-4N0-1M0). Expression analysis was performed using the 2-ΔΔCT method. The levels of ABPs in the blood serum were measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. No significant difference in the mRNA gene expression in tumor tissue of patients with T1-3N0M0 SCCLH and patients with T2-4N1-2M0 SCCLH was found. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T2-4N1-2M0 patients, the level of PFN1 was lower by 21% and the level of CAP1 was higher by 75% than those observed in T1-4N0M0 patients. The data obtained showed that RND3 is involved in the regulation of molecular cascades of SCCLH metastasis. PFN1 and CAP1 serum levels can be good classifiers of metastases in patients with SCCLH.
Subject(s)
Hypopharyngeal Neoplasms/metabolism , Laryngeal Neoplasms/metabolism , Microfilament Proteins/genetics , Adult , Aged , Carcinoma, Squamous Cell/pathology , Cell Cycle Proteins/analysis , Cell Cycle Proteins/blood , Cell Cycle Proteins/genetics , Cofilin 1/analysis , Cofilin 1/blood , Cofilin 1/genetics , Cytoskeletal Proteins/analysis , Cytoskeletal Proteins/blood , Cytoskeletal Proteins/genetics , Cytoskeleton/metabolism , Female , Head and Neck Neoplasms/pathology , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/genetics , Laryngeal Neoplasms/blood , Male , Microfilament Proteins/metabolism , Middle Aged , Profilins/analysis , Profilins/blood , Profilins/genetics , RNA, Messenger/genetics , Russia , Serum/metabolism , Signal Transduction/genetics , Snail Family Transcription Factors/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , rho GTP-Binding Proteins/geneticsABSTRACT
BACKGROUND: Patient prognosis in hypopharyngeal carcinoma remains difficult to predict, necessitating new, readily available biomarkers. OBJECTIVE: Platelet-lymphocyte ratio (PLR)'s effects on recurrence-free survival (RFS) and overall survival (OS) were evaluated in individuals undergoing radical resection for advanced hypopharyngeal squamous cell carcinoma (HSCC). METHODS: A total of 89 patients were retrospectively assessed. PLR, and derived neutrophil-lymphocyte (dNLR) and neutrophil-lymphocyte (NLR) ratios were determined based on complete blood count. Then, the prognostic values of PLR, dNLR and NLR were assessed by univariate and multivariate Cox regression analyses adjusted for disease-specific prognostic factors. Endpoints of interest were RFS and OS. RESULTS: The optimal cutoff of PLR was 98.815, based on which individuals were categorized into the high- (PLR ≥98.815) and low- (PLR <98.815) PLR groups. High PLR (p = .022) had a significant association with reduced RFS, which still showed significance in multivariable analysis (HR = 2.020, 95%CI: 1.076-3.794, p = .029). In univariate analysis, PLR (p = .046) and positive surgical margin (p = .021) also had significant associations with OS. CONCLUSION: Elevated PLR has associations with increased risk of recurrence and reduced survival in advanced HSCC cases undergoing radical resection. High presurgical PLR may independently predict RFS. Therefore, further multi-institutional prospective studies are needed to better characterize the role of pre-operative blood PLR as prognostic factors in HSCC.
Subject(s)
Hypopharyngeal Neoplasms/blood , Lymphocyte Count , Neck Dissection , Platelet Count , Squamous Cell Carcinoma of Head and Neck/blood , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/surgery , Laryngectomy , Male , Margins of Excision , Middle Aged , Neoplasm Recurrence, Local/mortality , Preoperative Care , Prognosis , ROC Curve , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/surgery , Survival AnalysisABSTRACT
BACKGROUND: There were heterogeneous or even conflicting data regarding the ability of platelet-to-lymphocyte ratio (PLR) for predicting the prognosis of laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC). The discrepancies were found to be largely due to the cutoff value of PLR. AIMS: The aims of this study were to rationally select an optimal PLR cutoff value and to analyze the relationship between pretreatment PLR and the prognosis. METHODS: A total of 180 male patients were eligible for this retrospective study. We included another 180 healthy male individuals as controls. The relationship between PLR and age in patients and the controls was determined. The optimal cutoff values of PLR were identified. PLR value was then dichotomized into two categories, and the relationship between PLR and the clinicopathologic parameters were calculated. Kaplan-Meier curves were used to evaluate the overall survival (OS), and the association between PLR and the OS was analyzed. RESULTS: The linear regression analysis showed a positive correlation between age and PLR in the control group, but not the patients. The optimal cutoff value of PLR was 112.5. The high PLR value group of patients exhibited significantly decreased OS. PLR was related to prognosis, as revealed by the univariate Cox regression. CONCLUSION: Patients with LHSCC have abnormal high PLR, and a high pretreatment PLR portends adverse survival.
Subject(s)
Carcinoma, Squamous Cell/blood , Hypopharyngeal Neoplasms/blood , Laryngeal Neoplasms/blood , Lymphocyte Count , Platelet Count , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/surgery , Kaplan-Meier Estimate , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Linear Models , Male , Middle Aged , Prognosis , Proportional Hazards Models , Reference Values , Retrospective StudiesABSTRACT
OBJECTIVES: To develop and validate a clinical prediction model (CPM) for survival in hypopharynx cancer, thereby aiming to improve individualized estimations of survival. METHODS: Retrospective cohort study of hypopharynx cancer patients. We randomly split the cohort into a derivation and validation dataset. The model was fitted on the derivation dataset and validated on the validation dataset. We used a Cox's proportional hazard model and least absolute shrinkage and selection operator (LASSO) selection. Performance (discrimination and calibration) of the CPM was tested. RESULTS: The final model consisted of gender, subsite, TNM classification, Adult Comorbidity Evaluation-27 score (ACE27), body mass index (BMI), hemoglobin, albumin, and leukocyte count. Of these, TNM classification, ACE27, BMI, hemoglobin, and albumin had independent significant associations with survival. The C Statistic was 0.62 after validation. The model could significantly identify clinical risk groups. CONCLUSIONS: ACE27, BMI, hemoglobin, and albumin are independent predictors of overall survival. The identification of high-risk patients can be used in the counseling process and tailoring of treatment strategy or follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2166-2172, 2020.
Subject(s)
Clinical Decision Rules , Hypopharyngeal Neoplasms/mortality , Risk Assessment/standards , Aged , Body Mass Index , Calibration , Female , Hemoglobins/analysis , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Serum Albumin/analysisABSTRACT
Serum neutrophil-to-lymphocytes ratio (NLR) is a potential predictive and prognostic marker in head and neck cancers. This study aimed to determine the role of pretreatment serum NLR in patients with hypopharyngeal cancer (HPC) treated with definitive chemoradiotherapy. We retrospectively investigated the correlation between clinicopathological parameters and NLR status and analysed its impact on therapeutic response and survival. A total of 120 patients treated at a single institution between 2009 and 2015 were included. The median follow-up time was 24.1 months. High NLR (NLR ≥ 4) was associated with advanced T classification (p = 0.01*) and advanced stage (p = 0.02*) based on chi-square test. We also found that high pretreatment NLR was correlated with poor treatment response (HR = 2.42, 95% CI: 1.08-5.44, p = 0.03*). Pretreatment NLR was also an independent prognostic factor for progression-free survival (HR = 1.71, 95% CI: 1.01-2.90, p = 0.046*) and overall survival (HR = 1.99, 95% CI: 1.21-3.28, p = 0.01*) while correcting for known prognostic factors. Overall, these findings support that NLR is a potential biomarker for host response to tumour aggressiveness, therapeutic response to chemoradiotherapy and survival in HPC patients. This study is limited by its retrospective nature and further validation is warranted.
Subject(s)
Hypopharyngeal Neoplasms/drug therapy , Hypopharyngeal Neoplasms/radiotherapy , Leukocyte Count , Neutrophils , Chemoradiotherapy , Female , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/mortality , Lymphocyte Count , Male , Middle Aged , Pilot Projects , Prognosis , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: The C-reactive protein/albumin (CRP/Alb) ratio has been recently established as a prognostic indicator in various cancer types. However, few reports regarding the prognostic value of the CRP/Alb ratio in head and neck cancer exist. This study aimed to investigate the significance of the CRP/Alb ratio in clinical outcomes after invasive surgery involving laryngectomy for hypopharyngeal and laryngeal cancer. METHODS: We evaluated 56 patients who underwent total laryngectomy or total pharyngolaryngectomy between 2003 and 2012. Univariate and multivariate analyses were retrospectively performed to examine the prognostic value of the CRP/Alb ratio in these patients. RESULTS: The optimal cutoff value of the CRP/Alb ratio was 0.32. Multivariate analysis showed that the CRP/Alb ratio was a significant and independent predictor of poor overall and disease-free survival. CONCLUSION: The CRP/Alb ratio may be a novel and useful indicator for predicting postoperative outcomes in patients with hypopharyngeal and laryngeal cancer.
Subject(s)
Albumins/metabolism , Biomarkers, Tumor/blood , C-Reactive Protein/metabolism , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/surgery , Laryngectomy/mortality , Aged , Cohort Studies , Disease-Free Survival , Female , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Hypopharynx/surgery , Japan , Kaplan-Meier Estimate , Laryngeal Neoplasms/blood , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngectomy/methods , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk Assessment , Survival Analysis , Treatment OutcomeABSTRACT
Laryngeal carcinoma is one of the most common tumors concerning otorhinolaryngology head and neck surgery, however, the pathogenesis of laryngeal carcinoma remains unclear. MicroRNAs (miRNAs) have been reported to play vital roles in the pathogenesis of laryngeal carcinoma Herein, the present study was designed to explore the function and mechanism of miRNA98 in hypopharyngeal carcinoma. In brief, qRTPCR, MTT assay, western blot analysis, Transwell assay and luciferase reporter assay were performed. Based on the results, miRNA98 expression was downregulated in patients with hypopharyngeal carcinoma. Downregulation of miRNA98 promoted cell growth and migration, and decreased the apoptotic rate of hypopharyngeal carcinoma cells. Overexpression of miRNA98 increased the apoptotic rate, and inhibited cell growth and migration of hypopharyngeal carcinoma cells. Moreover, luciferase reporter assays revealed that MTDH is a direct target of miRNA98 and overexpression of miRNA98 induced the protein expression of PTEN and suppressed that of PI3K and pAkt. siMTDH attenuated the anticancer effects of miRNA98 on hypopharyngeal carcinoma via the PTEN/AKT pathway. To the best of our knowledge, the present study confirmed for the first time that miRNA98 inhibits hypopharyngeal carcinoma cell proliferation and induces apoptosis via the PTEN/AKT pathway by MTDH.
Subject(s)
Carcinoma/genetics , Cell Adhesion Molecules/genetics , Gene Expression Regulation, Neoplastic , Hypopharyngeal Neoplasms/genetics , MicroRNAs/metabolism , Signal Transduction/genetics , Apoptosis/genetics , Carcinoma/blood , Carcinoma/pathology , Case-Control Studies , Cell Adhesion Molecules/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Disease Progression , Down-Regulation , Female , Gene Expression Profiling , Healthy Volunteers , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/pathology , Male , Membrane Proteins , MicroRNAs/blood , MicroRNAs/genetics , Neoplasm Invasiveness/pathology , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA-Binding ProteinsABSTRACT
OBJECTIVE: The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC. METHODS: Serum samples for the analysis of SCCA1, SCCA2 and SCC antigen were taken from head and neck SCC patients before treatment. Serum SCC antigen was assayed with a solid phase immunoradiometric assay. The SCCA1 and SCCA2 protein level was determined by a sandwich ELISA. RESULTS: Fifty-two of 96 cases (54%) showed evaluated serum SCC antigen levels above the upper limit. The serum SCCA2 level was significantly higher in the head and neck SCC patients than in control group, whereas there were no significant differences in the serum SCCA1 level between head and neck SCC patients and control group. 72% of head and neck SCC patients demonstrated SCCA2 levels higher than 0.15, whereas 68% of the control subjects had SCCA2 levels less than 0.15. CONCLUSION: The serum SCCA2 levels were increased during the progression of cancer and might be a useful tool for the management of head and neck SCC.
Subject(s)
Antigens, Neoplasm/blood , Head and Neck Neoplasms/blood , Serpins/blood , Squamous Cell Carcinoma of Head and Neck/blood , Adult , Aged , Aged, 80 and over , Case-Control Studies , Disease Progression , Female , Humans , Hypopharyngeal Neoplasms/blood , Laryngeal Neoplasms/blood , Male , Middle Aged , Mouth Neoplasms/blood , Nose Neoplasms/blood , Oropharyngeal Neoplasms/blood , Paranasal Sinus Neoplasms/blood , Young AdultABSTRACT
BACKGROUND/AIM: The purpose of this study is to investigate the prognostic significance of the pretreatment F-NLR score, which is based on fibrinogen (F) and neutrophil-to-lymphocyte ratio (NLR) in patients with advanced hypopharyngeal carcinoma (HPC). MATERIALS AND METHODS: A total of 111 advanced HPC patients treated with radiotherapy, chemoradiotherapy, or bioradiotherapy were classified into three groups: F-NLR score of 2 (fibrinogen ≥341 mg/dl and NLR≥3.59), score of 1 (fibrinogen ≥341 mg/dl or NLR≥3.59), and score of 0 (fibrinogen <341 mg/dl and NLR<3.59). RESULTS: F-NLR score of 2 was an independent prognostic factor for overall (OS) and progression-free survival (PFS) in patients with advanced HPC in the multivariate analysis. Both OS and PFS were significantly lower in patients with an F-NLR score of 2 than in those with an F-NLR score of 0. CONCLUSION: F-NLR score was useful to stratify patients to extract poor prognostic characteristics in patients with advanced HPC.
Subject(s)
Carcinoma, Squamous Cell/blood , Decision Support Techniques , Fibrinogen/analysis , Head and Neck Neoplasms/blood , Hypopharyngeal Neoplasms/blood , Lymphocytes , Neutrophils , Aged , Aged, 80 and over , Area Under Curve , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Disease Progression , Disease-Free Survival , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/therapy , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Hypopharyngeal Neoplasms/therapy , Kaplan-Meier Estimate , Lymphocyte Count , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Proportional Hazards Models , ROC Curve , Reproducibility of Results , Retrospective Studies , Risk Factors , Squamous Cell Carcinoma of Head and Neck , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying 'true' residual disease. METHODS: We prospectively recruited test (n=55) and validation (n=33) cohorts. HPV status was confirmed by E7 RT-PCR. We developed a novel amplicon-based next generation sequencing assay (HPV16-detect) to detect circulating HPV DNA. Circulating HPV DNA levels post-CCRT were correlated to disease response (PET-CT). RESULTS: In pre-CCRT plasma, HPV-detect demonstrated 100% sensitivity and 93% specificity, and 90% sensitivity and 100% specificity for the test (27 HPV+) and validation (20 HPV+) cohorts, respectively. Thirty-six out of 37 patients (test and validation cohort) with complete samples-set had negative HPV-detect at end of treatment. Six patients underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had no viable tumour. One patient had positive HPV-detect and positive PET-CT and liver biopsy, indicating 100% agreement for HPV-detect and residual cancer. CONCLUSIONS: We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response.
Subject(s)
Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , DNA, Viral/blood , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/therapy , Human papillomavirus 16/genetics , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/pathology , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/pathology , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/blood , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/therapy , Neck Dissection , Neoplasm, Residual , Oropharyngeal Neoplasms/blood , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/therapy , Prospective Studies , Sensitivity and Specificity , Treatment OutcomeABSTRACT
BACKGROUND: The use of plasma as a "liquid biopsy" has gained increasing attention. The purpose of the present study was to evaluate the diagnostic and prognostic utility of the perioperative detection and quantitation of mRNAs encoding human telomerase reverse transcriptase (hTERT) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in plasma from patients with cancer of the larynx or hypopharynx. METHODS: We recruited 47 patients with laryngeal cancer and 2 patients with hypopharyngeal cancer, plus 27 healthy subjects. A blood sample was taken from each patient before and after surgical resection of the tumor. We quantified hTERT mRNA and GAPDH mRNA in plasma by real-time polymerase chain reaction (PCR). RESULTS: Detection of hTERT mRNA before surgery had diagnostic value (sensitivity, 22%; specificity, 100%). Detection was more frequent in patients with supraglottic tumors than glottic tumors (p = .02) and was related to subsequent recurrence (p = .02). Preoperative levels of hTERT mRNA in plasma were higher in patients with subsequent recurrence (p = .046) and/or metastases (p = .047). The disease-free survival (DFS) and overall survival (OS) of patients with plasma samples positive for hTERT mRNA was poorer than that of patients with negative samples. Mean levels of plasma GAPDH mRNA in untreated patients were higher than in healthy subjects (p < .001). CONCLUSION: Detection and quantitation of hTERT and GAPDH mRNA in patients' plasma might be clinically significant in cases of laryngeal and hypopharyngeal cancer. © 2017 Wiley Periodicals, Inc. Head Neck 39: 647-655, 2017.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Hypopharyngeal Neoplasms/blood , Laryngeal Neoplasms/blood , RNA, Messenger/blood , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Case-Control Studies , Disease-Free Survival , Female , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Hypopharyngeal Neoplasms/surgery , Kaplan-Meier Estimate , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Male , Middle Aged , Perioperative Care/methods , Polymerase Chain Reaction/methods , Prognosis , Retrospective Studies , Spain , Statistics, Nonparametric , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: The purpose of this study was to analyze the relationship between pretreatment inflammatory markers and the prognosis of patients with oropharyngeal, hypopharyngeal, and laryngeal cancers. METHODS: The data for 285 patients treated with curative intent by concurrent chemoradiotherapy (CRT) were obtained and their pretreatment inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. RESULTS: Significant relationships were observed between a high NLR and oropharyngeal or hypopharyngeal cancer, T3 to T4, N2b to N3, and clinical stage III to IV, whereas significant relationships were observed between a high LMR and laryngeal cancer, T1 to T2, and clinical stage I to II. With regard to survival outcomes, a high NLR, a high PLR, and a low LMR were all significantly associated with decreases in overall survival (OS) and disease-free survival (DFS). Furthermore, multivariate analysis showed that LMR was an independent prognostic factor. CONCLUSION: Pretreatment LMR was found to be an independent prognostic factor for patients with head and neck cancers treated by concurrent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 39: 247-253, 2017.
Subject(s)
Chemoradiotherapy/methods , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/mortality , Inflammation Mediators/blood , Laryngectomy/methods , Adult , Aged , Aged, 80 and over , Cohort Studies , Databases, Factual , Disease-Free Survival , Female , Head and Neck Neoplasms/therapy , Hospitals, University , Humans , Hypopharyngeal Neoplasms/blood , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/therapy , Japan , Kaplan-Meier Estimate , Laryngeal Neoplasms/blood , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/therapy , Lymphocyte Count , Male , Middle Aged , Monocytes/cytology , Neck Dissection/methods , Oropharyngeal Neoplasms/blood , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/therapy , Platelet Count , Preoperative Care/methods , Proportional Hazards Models , ROC Curve , Retrospective Studies , Survival AnalysisABSTRACT
PURPOSE: Locally advanced carcinomas arising in the hypopharynx have been traditionally treated by resection of the hypopharynx, larynx, and cervical esophagus. However, the prognosis of these patients is still low. In the present study, we retrospectively analyzed the long-term survival of patients with locally advanced hypopharyngeal squamous cell carcinoma (HSCC) reconstructed by jejunal graft. METHODS: Between 2004 and 2014, 68 patients with HSCC were treated at Tottori University Hospital. Nine patients with synchronous esophageal cancer were excluded. We analyzed the overall survival of 59 patients with clinical stage III and IV HSCC who underwent pharyngo-laryngo-cervical esophagectomy with definitive tracheostomy followed by free jejunal graft reconstruction. Additionally, prognostic significances of preoperative patients' Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio (NLR), and prognostic nutritional index were analyzed. RESULTS: Postoperative complications occurred in 18.6 % of 59 patients. There were no cases of graft loss, and no patient died from complications. Preoperative poor performance status of patients was a risk factor for postoperative complications. The 5-year overall survival rate of the 59 patients was 46.1 %, and the median survival time was 28 months. In univariate and multivariate survival analyses, high GPS (1 or 2), and high NLR (≥5) were recognized as independent poor prognostic markers for patients with HSCCs. CONCLUSIONS: Pharyngo-laryngo-cervical esophagectomy followed by free jejunal reconstruction was performed safely. Additional treatment, such as chemoradiotherapy, should be introduced for patients with high preoperative GPS or NLR after curative operation.
Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/surgery , Hypopharyngeal Neoplasms/diagnosis , Hypopharyngeal Neoplasms/surgery , Neck Dissection , Aged , Carcinoma, Squamous Cell/blood , Female , Glasgow Outcome Scale , Humans , Hypopharyngeal Neoplasms/blood , Lymphocyte Count , Male , Middle Aged , Neoplasm Staging , Neutrophils , Nutritional Status , Prognosis , Retrospective Studies , Survival AnalysisABSTRACT
BACKGROUND: Hepatitis C virus (HCV) infection is associated with hepatocellular carcinoma and non-Hodgkin's lymphoma. In 2009, MD Anderson established the first US clinic for treating HCV-infected cancer patients, where we observed an unexpectedly large number of patients with head and neck cancers (HNCs). We sought to determine whether HCV is associated with HNCs. METHODS: In this case-control study, medical records of cancer patients tested for HCV antibodies at our center from 2004 through 2014 were identified. Case subjects had new-onset primary oropharyngeal or nonoropharyngeal (oral cavity, nasopharynx, hypopharynx, or larynx) HNCs. Control subjects had smoking-associated (lung, esophagus, or urinary bladder) cancers. Biopsy reports of oropharyngeal cancers tested for human papillomavirus (HPV) were reviewed. Patients with lymphoma were excluded. Multivariable logistic regression models were constructed. All statistical tests were two-sided. RESULTS: Of 34 545 cancer patients tested for HCV antibodies, 409 case subjects (164 oropharyngeal and 245 nonoropharyngeal) and 694 control subjects (378 lung, 168 esophagus, and 148 urinary bladder) were studied. The prevalence of HCV seropositivity was higher in oropharyngeal cancer patients (14.0%, 95% confidence interval [CI] = 8.7% to 19.4%, vs 6.5%, 95% CI = 4.6% to 8.3%), particularly HPV-positive oropharyngeal cancer patients (16.9%, 95% CI = 8.7% to 24.9%, vs 6.5%, 95% CI = 4.6% to 8.3%), and nonoropharyngeal HNC patients (20.0%, 95% CI = 14.9% to 25.0%, vs 6.5%, 95% CI = 4.6% to 8.3%) than in control subjects. Adjusted models showed a statistically significant association of HCV seropositivity with nonoropharyngeal (except nasopharyngeal) HNCs (odds ratio [OR] = 2.85, 95% CI = 1.38 to 5.88) and HPV-positive oropharyngeal cancers (OR = 2.97, 95% CI = 1.31 to 6.76). CONCLUSIONS: HCV is associated with nonoropharyngeal (except nasopharyngeal) and HPV-positive oropharyngeal HNCs. Further studies are required to explore the possible interaction between HCV and HPV, and the association between HCV and other HPV-related malignancies.
Subject(s)
Esophageal Neoplasms/blood , Hepacivirus/immunology , Hepatitis C Antibodies/blood , Hypopharyngeal Neoplasms/epidemiology , Laryngeal Neoplasms/epidemiology , Lung Neoplasms/blood , Mouth Neoplasms/epidemiology , Nasopharyngeal Neoplasms/epidemiology , Oropharyngeal Neoplasms/epidemiology , Urinary Bladder Neoplasms/blood , Aged , Case-Control Studies , Esophageal Neoplasms/etiology , Female , Humans , Hypopharyngeal Neoplasms/blood , Laryngeal Neoplasms/blood , Lung Neoplasms/etiology , Male , Middle Aged , Mouth Neoplasms/blood , Nasopharyngeal Neoplasms/blood , Oropharyngeal Neoplasms/blood , Papillomaviridae/immunology , Seroepidemiologic Studies , Smoking/adverse effects , Urinary Bladder Neoplasms/etiologyABSTRACT
Hypopharyngeal squamous cell carcinoma (HSCC) has very poor prognosis compared with other head and neck squamous cell carcinomas. Late-stage diagnosis of HSCC increases mortality. Therefore, more effective biomarkers for early diagnosis of HSCC are necessary. Unfortunately, appropriate biomarkers for clinical diagnosis and prognosis have not been identified yet. However, recent progresses in quantitative proteomics have offered opportunities to identify plasma proteins as biomarkers for HSCC. In the present study, plasma samples were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE), and differentially expressed proteins were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). A total of 26 proteins representing 12 unique gene products were identified. The up-regulation proteins were alpha-2-HS-glycoprotein (AHSG), complement C4-B, haptoglobin, C-reactive protein, and ceruloplasmin, whereas the down-regulation proteins were serum albumin, angiotensinogen, alpha-1-antichymotrypsin, Ig gamma-3 chain C region, fibrinogen gamma chain, apolipoprotein A-I, and Ig kappa chain C region. Among all the differentially expressed proteins, AHSG was validated by western blot and ELISA. The results were consistent with the data from 2D-DIGE, further suggesting that AHSG may be employed as a potential biomarker for the early diagnosis of HSCC. In summary, this study was the first to use 2D-DIGE and MALDI-TOF/TOF platform to identify the potential plasma biomarkers for HSCC. The plasma AHSG showed great potential for HSCC screening.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/diagnosis , Hypopharyngeal Neoplasms/diagnosis , alpha-2-HS-Glycoprotein/metabolism , Carcinoma, Squamous Cell/blood , Down-Regulation , Humans , Hypopharyngeal Neoplasms/blood , Proteomics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Up-RegulationABSTRACT
BACKGROUND: P16 and cyclin-D1 are cell cycle proteins commonly dysregulated in head and neck carcinoma. We assessed their expression, clinicopathological variables, and overall survival (OS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC). METHODS: Clinical characteristics and p16 and cyclin-D1 expression were evaluated in 101 patients with oropharyngeal SCC and 75 patients with hypopharyngeal SCC. Associations with OS were assessed using Cox regression and Kaplan-Meier analysis. RESULTS: Compared to oropharyngeal SCC, patients with hypopharyngeal SCC were older, men, ever-smokers with higher mean Charlson Comorbidity Index (CCI), lower p16 expression, and poorer median OS (24.8 vs 62.3 months; p < .01). In oropharyngeal SCC, CCI (p < .001), cyclin-D1 (hazard ratio [HR] = 3.55; p = .007), current smoking (HR = 5.72; p = .004), and former smoking (HR = 4.12; p = .035) were independently associated with OS. In hypopharyngeal SCC, only nodal and Eastern Cooperative Oncology Group status were associated with OS. CONCLUSION: In oropharyngeal SCC, cyclin-D1 expression is correlated with survival, whereas smoking status and CCI may allow further stratification of outcome.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/blood , Cyclin D1/metabolism , Human papillomavirus 16/metabolism , Hypopharyngeal Neoplasms/blood , Oropharyngeal Neoplasms/blood , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cohort Studies , Databases, Factual , Disease-Free Survival , Female , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Staging , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Prognosis , Proportional Hazards Models , Retrospective Studies , Singapore , Survival AnalysisABSTRACT
BACKGROUND: Head and neck squamous cell cancer (HNSCC) includes tumors of various anatomical sites sharing common etiological factors. Serum levels of MMP1, MMP2, and MMP9 were analyzed in patients with oropharyngeal, laryngeal, and hypopharyngeal carcinomas in an effort to elucidate the pathobiology and in order to find useful biomarkers of site-specific HNSCC. PATIENTS AND METHODS: The study group comprised of 46 patients with HNSCC (21 with oropharyngeal, 21 with laryngeal and 4 with hypopharyngeal cancer). Serum levels of MMP1, -2, and -9 were determined by the MAGPIX multiplex method. P16 protein was detected by immunohistochemistry. Serum levels of matrix metalloproteinases (MMPs) were correlated with clinicopathological features of carcinomas and were compared with respect to tumor site. RESULTS: Significant correlations were confirmed between p16 positivity and oropharyngeal cancer, MMP1 and p16 positivity, and recurrence and smoking. Statistically significant differences in serum levels of MMPs between cancer of different locations were not found. CONCLUSION: MMP1 expression is significantly affected by smoking habit and by p16 and might mediate etiopathogenetical process in cancerogenesis of HNSCC. Our pilot study did not establish any utility of MMP1, -2, or -9 in clinical practice as diagnostic/prognostic markers.
Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Head and Neck Neoplasms/blood , Matrix Metalloproteinase 1/blood , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 9/blood , Alcoholism , Cyclin-Dependent Kinase Inhibitor p16/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Hypopharyngeal Neoplasms/blood , Immunohistochemistry , Laryngeal Neoplasms/blood , Male , Middle Aged , Neoplasm Recurrence, Local , Oropharyngeal Neoplasms/blood , Pilot Projects , Preoperative Period , Prognosis , Smoking/adverse effects , Squamous Cell Carcinoma of Head and NeckABSTRACT
OBJECTIVE: To screen tumor biomarkers in the plasma close related with hypopharyngeal carcinoma. METHODS: Pooled plasma from 6 patients with hypopharyngeal carcinoma and 6 healthy individuals were collected. After removal of high-abundance plasma proteins, two-dimensional gel electrophoresis (2-DE) was performed to isolate the total proteins, and the protein spots with more than 2-fold differential expressions were detected by 2D analysis software followed by identification by MALDI-TOF/TOF mass spectrometer. Western blotting was performed to validate the expression level of α2-HS-glycoprotein. RESULTS: A total of 11 differentially expressed protein spots were selected, including 5 upregulated proteins and 6 downregulated proteins. MALDI-TOF/TOF identified the upregulated proteins in hypopharyngeal carcinoma patients as alpha-2-HS-glycoprotein and haptoglobin and downregulated ones as Ig kappa chain C region and apolipoprotein A-I. Western blotting demonstrated that α-2-HS- glycoprotein expression level was consistent with that detected by 2-DE. CONCLUSION: Patients with hypopharyngeal carcinoma show different plasma protein profiles from healthy individuals. These differentially expressed proteins may serve as potential specific tumor biomarkers for hypopharyngeal carcinoma.
Subject(s)
Biomarkers, Tumor/blood , Blood Proteins/metabolism , Hypopharyngeal Neoplasms/blood , Proteomics/methods , Humans , Male , Middle AgedABSTRACT
BACKGROUND: The immune system plays an important role in tumour immune surveillance. Head and neck squamous cell carcinoma patients are often immune compromised. OBJECTIVE: To chart the baseline levels of T-cell subpopulation frequencies in patients with cancer prior to treatment. SUBJECTS AND METHODS: Blood samples of patients were taken at the time of diagnosis, analysed with flowcytometry and compared with blood samples of healthy donors. RESULTS: Compared to healthy donors, a significant shift from naive to effector memory T cells was observed. This effect was most prominent in stage II patients. A similar shift from naive to effector memory T cells was noted in patients with oropharynx or larynx squamous cell carcinomas. Furthermore, the percentage of effector memory and effector T cells was higher in the group of patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas, compared with patients with human papillomavirus-negative tumours, suggestive of virus-induced T-cell activation. CONCLUSION: Here, we provide a simple and easily implementable tool to document T lymphocyte subsets in the peripheral blood of head and neck cancer patients, which might be useful for prognosis and/or therapy response prediction.