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BMC Cancer Apr 2021The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical significance of tumor-stroma ratio (TSR) has been examined in many tumors. Here we systematically reviewed all studies that evaluated TSR in head and neck cancer.
METHODS
Four databases (Scopus, Medline, PubMed and Web of Science) were searched using the term tumo(u)r-stroma ratio. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed.
RESULTS
TSR was studied in nine studies of different subsites (including cohorts of nasopharyngeal, oral, laryngeal and pharyngeal carcinomas). In all studies, TSR was evaluated using hematoxylin and eosin staining. Classifying tumors based on TSR seems to allow for identification of high-risk cases. In oral cancer, specifically, our meta-analysis showed that TSR is significantly associated with both cancer-related mortality (HR 2.10, 95%CI 1.56-2.84) and disease-free survival (HR 1.84, 95%CI 1.38-2.46).
CONCLUSIONS
The assessment of TSR has a promising prognostic value and can be implemented with minimum efforts in routine head and neck pathology.
Topics: Carcinoma, Squamous Cell; Disease-Free Survival; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Stromal Cells
PubMed: 33931044
DOI: 10.1186/s12885-021-08222-8 -
Medicine Oct 2020Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate the etiology, but the common carcinogenic mechanism remains unclear. Thus, we conducted the study to seek to find the common gene signatures and key functional pathways associated with oncogenesis and treatment in hypopharyngeal squamous cell carcinoma (HSCC) and ESCC by bioinformatic analysis.
METHODS
Three independent datasets (GSE2379, GSE20347, and GSE75241) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using database for annotation, visualization and integrated discovery (DAVID). Meanwhile, the protein-protein interaction network (PPI) constructed by search tool for the retrieval of interacting genes (STRING) was visualized using Cytoscape. Afterwards, the most key module and hub genes were extracted from the PPI network using the Molecular Complex Detection plugin. Moreover, the gene expression profiling interactive analysis (GEPIA) was applied to verify the expression differences and conduct the survival analyses of hub genes. Finally, the interaction network of miRNAs and hub genes constructed by encyclopedia of RNA interactomes (ENCORI) was visualized using Cytoscape.
RESULTS
A total of 43 DEGs were identified, comprising 25 upregulated genes and 18 downregulated genes, which were mainly involved in the extracellular matrix-receptor interaction, collagen metabolic, epidermis development, cell adhesion, and PI3K/Akt signaling pathways. Subsequently, 12 hub genes were obtained and survival analysis demonstrated SERPINE1 and SPP1 were closely related to poor prognosis of patients with HSCC and ESCC. Finally, hsa-miR-29c-3p, hsa-miR-29a-3p, and hsa-miR-29b-3p were confirmed as the top 3 interactive miRNAs that target the most hub genes according to the interaction network of miRNAs and hub genes.
CONCLUSION
The common gene signatures and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of HSCC and ESCC, and provide potential diagnostic and therapeutic targets.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Computational Biology; Databases, Genetic; Esophageal Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Humans; Pharyngeal Neoplasms; Prognosis
PubMed: 33080677
DOI: 10.1097/MD.0000000000022434 -
Cancers Apr 2020Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head-neck region and is characterized by the presence of squamous carcinomatous... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) is one of the main neoformations of the head-neck region and is characterized by the presence of squamous carcinomatous cells of the multi-layered epithelium lining the oral cavity, larynx, and pharynx. The annual incidence of squamous cell carcinoma of the head and neck (HNSCC) comprises approximately 600,000 new cases globally. Currently, the 5-year survival from HNSCC is less than 50%. Surgical, radiotherapy, and chemotherapy treatments strongly compromise patient quality of life. MicroRNAs (miRNAs) are a family of small noncoding endogenous RNAs that function in regulating gene expression by regulating several biological processes, including carcinogenesis. The main upregulated microRNAs associated with oral carcinoma are miR-21, miR-455-5p, miR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181, while the main downregulated miRNAs are miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b. miR-21 represents one of the first oncomirs studied. The present systematic review work was performed based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocol. A search was carried out in the PubMed and Scopus databases with the use of keywords. This search produced 628 records which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 7 included articles. The heterogeneity of the studies according to the odds ratio was high, with a Q value of 26.616 ( < 0.001), and the was 77.457% for specificity. The heterogeneity was high, with a Q value of 25.243 ( < 0.001) and the was 76.231% for sensitivity. The heterogeneity of data showed a Q value of 27.815 ( < 0.001) and the was 78.429%. Therefore, the random-effects model was selected. The diagnostic odds ratio was 7.620 (95% CI 3.613-16.070). The results showed that the sensitivity was 0.771 (95% CI 0.680-0.842) ( < 0.001) while, for specificity, we found 0.663 (95% CI 0.538-0.770) ( < 0.001). The negative likelihood ratio (NLR) was 0.321 (95% CI 0.186-0.554), and the positive likelihood ratio (PLR) was 2.144 (95% CI 1.563-2.943). The summary ROC plot demonstrates that the diagnostic test presents good specificity and sensitivity, and the area under the curve (AUC), as calculated from the graph, was 0.79.
PubMed: 32290144
DOI: 10.3390/cancers12040936 -
Cells Sep 2019To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous...
OBJECTIVES
To review the current knowledge regarding the involvement of human papilloma virus (HPV) infection and the immune system in the development of head and neck squamous cell carcinoma (HNSCC).
METHODS
An electronic literature search was conducted to identify articles published between 1990 and 2019 pertaining to tumor-infiltrating immune cells (TICs) in HNSCC using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Issues of clinical relevance, including tumor location, the number of tumor samples, the inclusion of additional specimens (dysplastic or normal mucosa), tumor size, methods used for HPV detection, relationship between antigen expression and patient characteristics (age, gender, smoking, alcohol consumption, etc.), and prognostic data (overall survival (OS) and recurrence-free survival (RFS)) were assessed by four blinded investigators.
RESULTS
The search identified 335 relevant studies, of which 41 met the inclusion criteria. Of these, 7 studies focused on the peripheral blood immune cell concentration in patients with HNSCC according to HPV status, and 36 studies investigated TICs in the intraepithelial and/or stromal compartment(s) according to HPV status. The immune cells studied were CD8+ T cells (N = 19), CD4+ T cells (N = 7), regulatory T cells (Tregs, N = 15), macrophages (N = 13), myeloid-derived suppressor cells (MDSCs, N = 4), and Langerhans cells (LCs, N = 2).
CONCLUSIONS
Irrespective of tumor location, CD8+ and CD4+ T cells appear to play a key role in the development of HPV-related HNSCC, and their infiltration is likely associated with a significant impact on OS and RFS. To date, the roles and prognostic value of Tregs, macrophages, DCs and MDSCs remain unclear.
Topics: Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Langerhans Cells; Macrophages; Male; Myeloid-Derived Suppressor Cells; Oropharyngeal Neoplasms; Oropharynx; Papillomaviridae; Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes, Regulatory
PubMed: 31510065
DOI: 10.3390/cells8091061 -
Journal of Clinical Medicine Feb 2019The aim of this systematic review with meta-analysis was to investigate the available literature on transoral approaches in the treatment of hypopharyngeal squamous cell... (Review)
Review
The aim of this systematic review with meta-analysis was to investigate the available literature on transoral approaches in the treatment of hypopharyngeal squamous cell carcinoma, with a special focus on transoral robotic surgery (TORS). A systematic review was conducted according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) check-list, and 15 studies were included. Five of the included studies evaluated TORS, while ten studies focused on transoral laser microsurgery (TLM) for the treatment of early or advanced stage hypopharyngeal cancer. Overall, survival rates of TLM and TORS studies, analyzed together in the cumulative meta-analysis, were 66.4% (95% confidence interval (CI) 54.3%⁻76.7%) at 36+ months of follow up. The TORS subgroup showed a higher cumulative survival rate (85.5%, 95% CI 55.8%⁻96.5%) compared to TLM (58.5%, 95% CI 46.6%⁻69.6%). Cumulative data showed that 29.3% (95% CI 24.0%⁻35.3%) of deaths were attributable to cancer. The results were similar between TLM and TORS studies. The larynx function preservation cumulative rate was 94.3% (95% CI 91.8%⁻96.1%). The results were similar among the two subgroups. The present review supports the use of transoral approaches in the treatment of hypopharyngeal cancer. TORS is oncologically sound and provides excellent functional results with low complication rates.
PubMed: 30781660
DOI: 10.3390/jcm8020256 -
PloS One 2019Nasopharyngeal cancer (NPC), despite being one of the most malignant head and neck carcinomas (HNC), lacks comprehensive prognostic biomarkers that predict patient... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nasopharyngeal cancer (NPC), despite being one of the most malignant head and neck carcinomas (HNC), lacks comprehensive prognostic biomarkers that predict patient survival. Therefore, this systematic review and meta-analysis is aimed to evaluate the potential prognostic value of miRNAs as prognostic biomarkers in NPC.
METHODS
PRISMA guidelines were used to conduct this systematic review and meta-analysis study. Permutations of multiple "search key-words" were used for the search strategy, which was limited to articles published between January 2012 and March 2018. The retrieved articles were meticulously searched with multi-level screening by two reviewers and confirmed by other reviewers. Meta-analysis was performed using Hazard Ratios (HR) and associated 95% Confidence Interval (CI) of survival obtained from previously published studies. Publication bias was assessed by Egger's bias indicator test and funnel plot symmetry.
RESULTS
A total of 5069 patients across 21 studies were considered eligible for inclusion in the systematic review, with 65 miRNAs being evaluated in the subsequent meta-analysis. Most articles included in this study originated from China and one study from North Africa. The forest plot was generated using cumulated survival data, resulting in a pooled HR value of 1.196 (95% CI: 0.893-1.601) indicating that the upregulated miRNAs increased the likelihood of death of NPC patients by 19%.
CONCLUSION
To our knowledge, this is the first meta-analysis that examines the prognostic effectiveness of miRNAs as biomarkers in NPC patients. We noted that the combined effect estimate of HR across multiple studies indicated that increased miRNA expression in NPC potentially leads to poor overall survival. However, further large-scale prospective studies on the clinical significance of the miRNAs, with sizable cohorts are necessary in order to obtain conclusive results.
Topics: Biomarkers, Tumor; Humans; MicroRNAs; Nasopharyngeal Neoplasms; Nasopharynx; Prognosis; Survival Analysis
PubMed: 30735523
DOI: 10.1371/journal.pone.0209760 -
PloS One 2018Technological advancements in treatment planning and delivery have propelled the use of intensity-modulated radiation therapy (IMRT) in head and neck squamous cell... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analyses of intensity-modulated radiation therapy versus conventional two-dimensional and/or or three-dimensional radiotherapy in curative-intent management of head and neck squamous cell carcinoma.
INTRODUCTION
Technological advancements in treatment planning and delivery have propelled the use of intensity-modulated radiation therapy (IMRT) in head and neck squamous cell carcinoma (HNSCC). This review compares IMRT with conventional two-dimensional (2D) and/or three-dimensional (3D) radiotherapy (RT) in curative-intent management of HNSCC.
METHODS
Only randomized controlled trials (RCTs) offering curative-intent RT in patients with non-metastatic HNSCC were included. Outcome data was extracted independently by two reviewers, pooled using the Cochrane methodology, and expressed as risk ratio (RR) or hazard ratio (HR) as appropriate with 95% confidence intervals (CIs). Xerostomia was the primary outcome of interest whereas loco-regional control, overall survival and quality-of-life (QOL) were secondary endpoints.
RESULTS
Seven RCTs involving 1155 patients directly comparing IMRT with 2D/3D-RT in HNSCC were included. The primary objective in five of seven index RCTs was reduction in xerostomia, with only one trial each using loco-regional control and overall survival as primary endpoints for sample size calculation. The use of IMRT was associated with a 36% relative risk reduction in ≥grade 2 acute xerostomia (RR = 0.64, 95%CI = 0.49-0.84; p = 0.001) compared to 2D/3D-RT. More importantly, IMRT significantly reduced the risk of ≥grade 2 late xerostomia (RR = 0.44, 95%CI = 0.34-0.57; p = 0.00001) compared to non-IMRT techniques at all time-points. Within the limitations of inadequate sample size and low statistical power, IMRT also resulted in 24% relative reduction in the risk of loco-regional relapse (HR = 0.76, 0.57-1.01; p = 0.06) and 30% relative reduction in risk of death (HR = 0.70, 95%CI = 0.57-0.88; p = 0.002) compared to 2D/3D-RT. However, this benefit of IMRT for loco-regional control and overall survival was limited to nasopharyngeal cancer patients alone, with no significant difference in efficacy between the two techniques in patients with cancers of the laryngo-pharynx in this analysis, highlighting the inconsistency in results of subgroup analyses stratified by primary site. Inadequate reporting of data precluded statistically pooling of results for QOL outcomes.
CONCLUSIONS
There is consistent moderate-quality evidence that IMRT significantly reduces the risk of moderate to severe acute and late xerostomia compared to 2D/3D-RT in curative-intent radiotherapeutic management of HNSCC. However, the quality of evidence regarding the superiority of IMRT over conventional techniques for disease-related endpoints is rather low due to relative lack of power and inconsistency of results precluding robust conclusions.
Topics: Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Radiotherapy, Intensity-Modulated; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck; Treatment Outcome
PubMed: 29979726
DOI: 10.1371/journal.pone.0200137 -
World Journal of Surgical Oncology Jul 2016Solitary splenic metastases are a rare occurrence, and the nasopharyngeal carcinoma represents one of the most uncommon primary sources. The present study aimed to... (Review)
Review
BACKGROUND
Solitary splenic metastases are a rare occurrence, and the nasopharyngeal carcinoma represents one of the most uncommon primary sources. The present study aimed to describe a rare case of a solitary single splenic metastasis from nasopharyngeal carcinoma and to assess the number of cases of isolated nasopharyngeal carcinoma metastases to the spleen reported in the literature.
MAIN BODY
We describe the case of a 56-year-old man with a history of nasopharyngeal carcinoma and complete remission after chemo-radiotherapy. Three months after complete remission, positron emission tomography/computed tomography scan revealed a hypermetabolic splenic lesion without increased metabolic activity in other areas. After laparoscopic splenectomy, the pathology report confirmed a single splenic metastasis from undifferentiated carcinoma of the nasopharyngeal type. The postoperative period was uneventful. We also performed a systematic review of the literature using MEDLINE and Google Scholar databases. All articles reporting cases of splenic metastases from nasopharyngeal carcinoma, with or without histologic confirmation, were evaluated. The literature search yielded 15 relevant articles, which were very heterogeneous in their aims and methods and described only 25 cases of splenic metastases from nasopharyngeal carcinoma.
CONCLUSION
The present review shows that solitary splenic metastases from nasopharyngeal carcinoma are a rare event, but it should be considered in patients presenting with splenic lesions at imaging and a history of primary or recurrent nasopharyngeal carcinoma. No evidence supports a negative impact of splenectomy in patients with solitary splenic metastasis from nasopharyngeal carcinoma.
Topics: Biopsy; Carcinoma; Chemoradiotherapy; Herpesvirus 4, Human; Humans; Laparoscopy; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Neoadjuvant Therapy; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Rare Diseases; Splenectomy; Splenic Neoplasms; Treatment Outcome
PubMed: 27422630
DOI: 10.1186/s12957-016-0941-2 -
Brazilian Journal of Otorhinolaryngology 2015Human papillomavirus has been associated with head and neck squamous cell carcinoma. However, there is no conclusive evidence on the prevalence of oral or pharyngeal... (Review)
Review
INTRODUCTION
Human papillomavirus has been associated with head and neck squamous cell carcinoma. However, there is no conclusive evidence on the prevalence of oral or pharyngeal infection by human papillomavirus in the Brazilian population.
OBJECTIVE
To determine the rate of human papillomavirus infection in the Brazilian population.
METHODS
Systematic review of published articles. Medline, The Cochrane Library, Embase, Lilacs (Latin American and Caribbean Health Sciences) and Scielo electronic databases were searched. The search included published articles up to December 2014 in Portuguese, Spanish and English. A wide search strategy was employed in order to avoid publication biases and to assess studies dealing only with oral and/or oropharyngeal human papillomavirus infections in the Brazilian population.
RESULTS
A total of 42 articles included 4066 enrolled patients. It was observed that oral or oropharyngeal human papillomavirus infections were identified in 738 patients (18.2%; IC 95 17.6-18.8), varying between 0.0% and 91.9%. The prevalences of oral or oropharyngeal human papillomavirus infections were respectively 6.2%, 44.6%, 44.4%, 27.4%, 38.5% and 11.9% for healthy people, those with benign oral lesions, pre-malignant lesions, oral or oropharyngeal squamous cell carcinoma, risk groups (patients with genital human papillomavirus lesions or infected partners) and immunocompromised patients. The risk of human papillomavirus infection was estimated for each subgroup and it was evident that, when compared to the healthy population, the risk of human papillomavirus infection was approximately 1.5-9.0 times higher, especially in patients with an immunodeficiency, oral lesions and squamous cell carcinoma. The rates of the most well-known oncogenic types (human papillomavirus 16 and/or 18) also show this increased risk.
CONCLUSIONS
Globally, the Brazilian healthy population has a very low oral human papillomavirus infection rate. Other groups, such as at-risk patients or their partners, immunocompromised patients, people with oral lesions and patients with oral cavity or oropharyngeal squamous cell carcinoma have a high risk of human papillomavirus infection.
Topics: Brazil; Carcinoma, Squamous Cell; Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Prevalence
PubMed: 26248966
DOI: 10.1016/j.bjorl.2015.04.001 -
BMC Cancer Dec 2014Infection with human papillomavirus (HPV) is necessary for the development of cervical carcinoma. By contrast, the role of HPV in the pathogenesis of other malignancies,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Infection with human papillomavirus (HPV) is necessary for the development of cervical carcinoma. By contrast, the role of HPV in the pathogenesis of other malignancies, such as head and neck cancers, is less well characterised. This study aimed to address key information gaps by conducting a systematic review and meta-analysis of the prevalence of HPV infection in head and neck cancers, focusing on data for European populations.
METHODS
MEDLINE, Embase and grey literature sources were systematically searched for primary studies that were published in English between July 2002 and July 2012, and which reported on the prevalence of HPV infection in head and neck cancers in European populations. Studies on non-European populations, those not published in English, and those assessing patients co-infected with human immunodeficiency virus were excluded. Eligible studies were combined in a meta-analysis. In addition, the potential statistical association between the head and neck cancers and certain HPV types was investigated.
RESULTS
Thirty-nine publications met the inclusion criteria. The prevalence of HPV of any type in 3,649 patients with head and neck cancers was 40.0% (95% confidence interval, 34.6% to 45.5%), and was highest in tonsillar cancer (66.4%) and lowest in pharyngeal (15.3%) and tongue (25.7%) cancers. There were no statistically significant associations between the HPV types analysed and the geographical setting, type of sample analysed or type of primer used to analyse samples in head and neck cancers.
CONCLUSIONS
The prevalence of HPV infection in European patients with head and neck cancers is high but varies between the different anatomical sites of these malignancies. There appears to be no association between HPV type and geographical setting, type of samples analysed or type of primer used to analyse samples in such cancers.
Topics: Europe; Head and Neck Neoplasms; Humans; Papillomaviridae; Papillomavirus Infections; Prevalence; White People
PubMed: 25515630
DOI: 10.1186/1471-2407-14-968