Prognosis Of Head And Neck Cancer Research Articles

Role of N6-methyladenosine methylation in head and neck cancer and its regulation of innate immune pathways.

N6-methyladenosine (m6A) is considered the most prevalent methylation modification in messenger RNA (mRNA) that critically impacts head and neck cancer (HNC) pathogenesis and development. Alterations of m6A methylation related proteins are closely related to the progression, therapeutic effect, and prognosis of HNC. The human innate immune system activates immune pathways through pattern recognition receptors, which can not only resist pathogen infection, but also play a vital role in tumor immunity. Emerging evidence has confirmed that m6A methylation affects the activation of innate immune pathways such as TLR, cGAS-STING, and NLR by regulating RNA metabolism, revealing its potential mechanisms in the innate immune response of tumor cells. However, the relevant research is still in its infancy. This review elaborates the biological significance of RNA m6A methylation in HNC and discusses its potential regulatory relationship with TLR, cGAS-STING, and NLR pathways, providing a new perspective for in-depth understanding of the role of RNA methylation in the innate immune mechanism and therapeutic application of HNC.

Association of the cytochrome P450 and arylamine N-acetyltransferase gene polymorphisms with the incidence of head and neck cancer in Polish population.

Head and neck cancer (HNC) is one of the most common cancers. Most exogenous HNC is head and neck squamous cell carcinomas. Scientists are striving to develop diagnostic tests that will allow the prognosis of HNC. The aim of the study was to determine the risk of HNC. The research concerned changes caused by polymorphisms in genes encoding proteins responsible for the metabolism of xenobiotics. In group of 280 patients with HNC, the occurrence of polymorphic variants in NAT1(rs72554606), NAT2(rs1799930), CYP1A(rs1799814), CYP2D(rs3892097) were studied with TaqMan technique. The control group consisted of 260 cancer free people. The TNM scale was analyzed. Gene interactions of genotyped polymorphisms were investigated. The effects of smoking and alcohol consumption on HNC were assessed. The results indicated an increased risk of HNC in NAT1 polymorphisms in the GC genotype (OR = 1.772, 95% CI: 1.184-2.651, p = 0.005) and NAT2 polymorphism in the GA genotype (OR = 1.506, 95% CI: 1.023-2.216, p = 0.037). The protective phenomenon in the CYP1A polymorphism the GT genotype (OR = 0.587, 95% CI: 0.381-0.903, p = 0.015) and the TT genotype (OR = 0.268, 95% CI: 0.159-0.452, p = 0.001). The coexistence of GA-GC polymorphisms (OR = 2.687, 95% CI: 1.387-5.205, p = 0.003) in NAT2-NAT1 genes increases the risk of HNC. Risk-reducing effect in the polymorphism GG-GT (OR = 0.340, 95% CI: 0.149-0.800, p = 0.011), GG-TT (OR = 0.077, 95% CI: 0.028-0.215, p < 0.0001), GA-TT (OR = 0.250, 95% CI: 0.100-0.622, p = 0.002), AA-GT (OR = 0.276, 95% CI: 0.112-0.676, p = 0.002) in NAT2-CYP1A genes. In the CYP2D-CYP1A genes in the polymorphisms CT-CC (OR = 0.338, 95% CI: 0.132-0.870, p = 0.020), TT-GG (OR = 0.100, 95% CI: 0.027-0.359, p = 0.001), TT-GC (OR = 0.190, 95% CI: 0.072-0.502, p = 0.0004), TT-CC (OR = 0.305, 95% CI: 0.107-0.868, p = 0.024). Correlation was noted between cigarette smoking and HNC (OR = 7.297, 95% CI: 4.989-10.674, p < 0.0001) and consuming alcohol (OR = 1.572, 95% CI: 1.003-2.464, p = 0.047). The CYP1A polymorphism shows a protective association with HNC. On the other hand, NAT2, NAT1 polymorphism influence the susceptibility to developing HNC. The coexistence of the NAT2-NAT1 genotypes increases the risk of HNC. In contrast, NAT1-CYP1A and CYP1A-CYP2D reduce this risk. Smoking and alcohol consumption increase the incidence of HNC. Int J Occup Med Environ Health. 2023;36(6):812-24.

The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

The Utility of Oncology Information Systems for Prognostic Modelling in Head and Neck Cancer

Cancer centres rely on electronic information in oncology information systems (OIS) to guide patient care. We investigated the completeness and accuracy of routinely collected head and neck cancer (HNC) data sourced from an OIS for suitability in prognostic modelling and other research. Three hundred and fifty-three adults diagnosed from 2000 to 2017 with head and neck squamous cell carcinoma, treated with radiotherapy, were eligible. Thirteen clinically relevant variables in HNC prognosis were extracted from a single-centre OIS and compared to that compiled separately in a research dataset. These two datasets were compared for agreement using Cohen’s kappa coefficient for categorical variables, and intraclass correlation coefficients for continuous variables. Research data was 96% complete compared to 84% for OIS data. Agreement was perfect for gender (κ = 1.000), high for age (κ = 0.993), site (κ = 0.992), T (κ = 0.851) and N (κ = 0.812) stage, radiotherapy dose (κ = 0.889), fractions (κ = 0.856), and duration (κ = 0.818), and chemotherapy treatment (κ = 0.871), substantial for overall stage (κ = 0.791) and vital status (κ = 0.689), moderate for grade (κ = 0.547), and poor for performance status (κ = 0.110). Thirty-one other variables were poorly captured and could not be statistically compared. Documentation of clinical information within the OIS for HNC patients is routine practice; however, OIS data was less correct and complete than data collected for research purposes. Substandard collection of routine data may hinder advancements in patient care. Improved data entry, integration with clinical activities and workflows, system usability, data dictionaries, and training are necessary for OIS data to generate robust research. Data mining from clinical documents may supplement structured data collection.

Integrative Analysis Identified CD38 As a Key Node That Correlates Highly with Immunophenotype, Chemoradiotherapy Resistance, And Prognosis of Head and Neck Cancer.

Head and neck cancer (HNC) is mainly treated by surgery, radiotherapy, and adjuvant chemotherapy; however, the prognosis of some patients with HNC is poor because of radiotherapy and chemotherapy resistance. In recent years, anti‑PD‑1 monoclonal antibodies have shown certain efficacy, and a change of the tumor immune microenvironment is the main reason for the failure of HNC immunotherapy. The present study aimed to identify and verify that CD38, which is closely related to the prognosis of HNC, is a potential biological marker of radiotherapy and chemotherapy resistance and PD-L1 immunotherapy resistance via a comprehensive bioinformatic analysis in The Cancer Genome Atlas and Gene Expression Omnibus databases. According to the UALCAN database, the transcript level of CD38 in HNC was analyzed using cluster analysis, and the expression of CD38 mRNA in HNC was detected using the Oncomine database. The characteristics of CD38-related oncogenes were identified by gene cluster enrichment analysis in LinkedOmics. The R2 and SEER databases were used to further evaluate the prognostic significance of the CD38 gene in HNC using receiver operating characteristic curve analysis of Kaplan-Meier (KM) survival and the clinical characteristics of the subjects. The protein-protein interaction network of the top 50 genes showing significant positive correlations with CD38 in HNC was analyzed using STRING. Finally, we used a nasopharyngeal carcinoma (NPC) cell line to verify the biological function. The results showed that the levels of CD38 mRNA expression in patients with HNC were significantly higher than those in healthy controls. The levels of CD38 mRNA expression in patients with HNC of different ages, sexes, and races were significantly higher than those in the healthy controls. CD38 is an independent prognostic factor for HNC, and high expression of CD38 indicates poor prognosis. CD38 expression correlated positively with the markers of many kinds of immune cells, and correlated significantly with the expression of PD-L1. We found that the high expression of CD38 suggested a poor prognosis in the subgroup of tumors treated with chemotherapeutic drugs in the G1/S phase. We used HNC cell lines to verify that the high expression of CD38 promoted the proliferation of NPC cells and produced radiotherapy tolerance. Through comprehensive bioinformatics analysis, we suggested that CD38 is a key gene involved in radiotherapy, chemotherapy, and immune drug resistance in HNC. This study provides a reliable biomarker to predict the prognosis of patients with HNC and a reference for clinical comprehensive treatment of HNC. Individualization combined with CD38 monoclonal antibodies might provide a promising treatment strategy for this fatal disease, and this comprehensive treatment might reduce the damage to normal tissue and improve the prognosis and quality of life of patients with HNC.

GPRASP1 is a candidate anti-oncogene and correlates with immune microenvironment and immunotherapeutic efficiency in head and neck cancer.

G-protein-coupled receptor-associated sorting protein 1 (GPRASP1) plays an important role in tumorigenesis. However, GPRASP1 specific role has not been clarified in head and neck cancer (HNC). HNC RNA sequencing (RNA-seq) datasets, DNA methylation data, somatic mutation data, copy number variation (CNV) data, and corresponding clinicopathologic information were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A comprehensive evaluation was performed to explore the relationship of GPRASP1 expression with clinicopathologic characteristics, CNV, and DNA methylation. Additionally, we employed HNC tissue microarray (TMA) to further confirm the relation between GPRASP1 expression and clinical features. Then, we systematically associated the GPRASP1 with immunological properties from numerous perspectives, such as immune cell infiltration, immune-related pathways, immune checkpoint inhibitors (ICIs), immunomodulators, immunogenicity, and immunotherapy. Analyzing TCGA, GEO, and TMA datasets, GPRASP1 is significantly down-regulated in HNC compared to normal tissues. The expression of GPRASP1 is significantly negatively correlated with clinical features (perineural invasion, histologic grade, T stage, and TNM stage), and is an independent predictor of favorable prognosis, regardless of other clinicopathological features (HR: 0.42, 95% CI 0.20-0.91, p=0.028). The etiological investigation found that the abnormal expression of GPRASP1 was related to DNA methylation, not CMV. Subsequently, the high expression of GPRASP1 was significantly correlated with immune cell infiltration (CD8+ T cell, tumor infiltrating lymphocyte), immune-related pathways (cytolytic activity, check-point, human leukocyte antigen), ICIs (CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT), immunomodulators (CCR4/5, CXCL9, CXCR3/4/5), and immunogenicity (immune score, neoantigen, tumor mutation burden). Finally, immunophenoscore and tumor immune dysfunction and exclusion analysis demonstrated that GPRASP1 expression levels can accurately predict the immunotherapeutic response. GPRASP1 is a promising candidate biomarker that plays a role in the occurrence, development, and prognosis of HNC. Evaluating GPRASP1 expression will aid in the characterization of tumor microenvironment infiltration and orient more efficient immunotherapy strategies.

Nutritional status at diagnosis is prognostic for pharyngeal cancer patients: a retrospective study.

Malnutrition in head and neck cancer (HNC) patients is associated with increased morbidity and mortality. Several nutrition indicators have been reported to be related to the prognosis of HNC. However, the prognostic effect of these multiple nutrition factors in HNC is not well elucidated. The aim of this study was to evaluate the prognostic effect of these factors, including the novel hemoglobin, albumin, lymphocyte, and platelet (HALP) score, for pharyngeal cancers. From 2008 to 2019, a total of 319 pharyngeal cancer patients were recruited. We collected adult patients with a diagnosis of nasopharyngeal carcinoma, oropharyngeal carcinoma and hypopharyngeal carcinoma. Patients who completed definite staging workup and treatment were selected for analysis. We traced nutritional and hematological parameters, including body mass index (BMI), albumin, and complete blood count, for survival analysis. We found that multiple nutritional markers, including BMI, hemoglobin, albumin, prognostic nutritional index (PNI), nutritional risk index (NRI) and HALP score, were important predictors for pharyngeal cancers in univariate Cox regression analysis. In multivariate analysis, we found that the HALP score was still an independent factor (HR: 1.62, 1.13-2.32 for overall survival [OS]) after adjusting of gender, age, cancer site, clinical stage, and BMI. The PNI was the most important independent factor for OS (HR: 3.12, 2.18-4.47) and cancer-specific survival (HR: 2.88, 1.88-4.41) in multivariate analysis. We found that multiple nutrition markers, including BMI, hemoglobin, albumin, PNI, NRI and HALP score, are important predictors for pharyngeal cancers. This is the first report confirming the prognostic effect of the HALP score for HNCs. Nutritional status at diagnosis should be given more attention in pharyngeal cancer patients.

The impact of radiation induced lymphopenia in the prognosis of head and neck cancer: A systematic review and meta-analysis

ObjectivesRadiotherapy is a key part of head and neck cancer (HNC) treatment. Radiation induced lymphopenia (RIL) is a severe complication of radiotherapy. The aim of this study was to evaluate the prognostic role of RIL in HNC patients. MethodWe conducted a PRISMA guideline based systematic review and meta-analysis. The studies were identified on the PubMed, Embase and Cochrane Library from 2007 to October 2021. The quality of each study was assessed by Newcastle-Ottawa Quality Assessment Form for Cohort Studies (NOS). ResultsThere were 8 studies with 2,733 samples finally included in current study. The meta-analysis showed that the odds ratio of developing grade 3–4 RIL was 13.49 (95%CI = 7.03–25.89, I2 = 94%). The incidence rate of grade 3–4 RIL ranged from 73%-88%. Multivariate meta-analysis found that the RIL significantly decreased the overall survival (HR = 2.94, 95%CI = 1.83–4.74, I2 = 0%) and distant metastasis free survival of HNC (HR = 3.79, 95%CI = 2.06–6.97, I2 = 0%). After sensitivity analysis and excluding a potential study that caused heterogeneity, the new pooled multivariate meta-analysis showed RIL was a risk factor to the progression free survival of HNC patients (HR = 3.16, 95%CI = 1.77–5.63, I2 = 0%). ConclusionThis is the first meta-analysis which showed severe RIL decreased the overall survival and promoted the progression of HNC patients. Future large-scale prospective studies are required to evaluate the association between severe RIL and the prognosis of HNC.

Application of PET/CT-based deep learning radiomics in head and neck cancer prognosis: a systematic review

Background: Radiomics and deep learning have been widely investigated in the quantitative analysis of medical images. Deep learning radiomics (DLR), combining the strengths of both methods, is increasingly used in head and neck cancer (HNC). This systematic review was aimed at evaluating existing studies and assessing the potential application of DLR in HNC prognosis. Materials and methods: The PubMed, Embase, Scopus, Web of Science, and Cochrane databases were searched for articles published in the past 10 years with the keywords “radiomics,” “deep learning,” and “head and neck cancer” (and synonyms). Two independent reviewers searched, screened, and reviewed the English literature. The methodological quality of each article was evaluated with the Radiomics Quality Score (RQS). Data from the studies were extracted and collected in tables. A systematic review of radiomics prognostic prediction models for HNC incorporating deep learning techniques is presented. Result: A total of eight studies, published in 2012–2022, with a varying number of patients (59–707 cases), were included. Each study used deep learning; three studies performed automatic segmentation of regions of interest (ROI), and the Dice score range for automatic segmentation was 0.75–0.81. Four studies involved extraction of deep learning features, one study combined different modality features, and two studies performed predictive model building. The range of the area under the curve (AUC) was 0.84–0.96, the range of the concordance index (C-index) was 0.72–0.82, and the range of model accuracy (ACC) was 0.72–0.96. The median total RQS for these studies was 13 (10–15), corresponding to a percentage of 36.11% (27.78%–41.67). Low scores were due to a lack of prospective design, cost-effectiveness analysis, detection and discussion of biologically relevant factors, and external validation. Conclusion: DLR has potential to improve model performance in HNC prognosis.

TXNIP, CXCL1, and AREG as key genes in formaldehyde-induced head and neck carcinoma: an in silico analysis

Background Reports have shown that formaldehyde (FA) can induce malignant transformation in cells via complicated mechanisms. Therefore, we aimed to investigate the possible molecules, pathways, and therapeutic agents for FA-induced head and neck cancer (HNC) by using bioinformatics approaches. Methods High throughput data were analyzed to screen the differentially expressed genes (DEGs) between FA-treated nasal epithelium cells and controls. Then, the functions of the DEGs were annotated and the hub genes, as well as the key genes, were further screened out. Afterwards, potential drugs were predicted by using the connectivity map (CMAP) tool. Results The information of a microarray-based dataset GSE21477 was extracted and analyzed. A total of 210 upregulated and 83 downregulated DEGs were generated, which might be enriched in various pathways, such as Cytokine–cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Among these DEGs, three hub genes including TXNIP, CXCL1, and AREG, were identified as the key genes because they might affect the prognosis of HNC. Finally, a major active ingredient of blister beetles, Cantharidin, was predicted to be one of the potential drugs reversing FA-induced malignant transformation in head and neck epithelium cells. Conclusion The present analysis gave us a novel insight into the mechanisms of FA-induced malignant transformation in head and neck epithelium cells, and predicted several small agents for the prevention or treatment of HNC. Future experiment studies are warranted to validate the findings.

Ubiquitin Carboxyl-Terminal Hydrolases and Human Malignancies: The Novel Prognostic and Therapeutic Implications for Head and Neck Cancer.

Ubiquitin C-terminal hydrolases (UCHs), a subfamily of deubiquitinating enzymes (DUBs), have been found in a variety of tumor entities and play distinct roles in the pathogenesis and development of various cancers including head and neck cancer (HNC). HNC is a heterogeneous disease arising from the mucosal epithelia of the upper aerodigestive tract, including different anatomic sites, distinct histopathologic types, as well as human papillomavirus (HPV)-positive and negative subgroups. Despite advances in multi-disciplinary treatment for HNC, the long-term survival rate of patients with HNC remains low. Emerging evidence has revealed the members of UCHs are associated with the pathogenesis and clinical prognosis of HNC, which highlights the prognostic and therapeutic implications of UCHs for patients with HNC. In this review, we summarize the physiological and pathological functions of the UCHs family, which provides enlightenment of potential mechanisms of UCHs family in HNC pathogenesis and highlights the potential consideration of UCHs as attractive drug targets.

Elderly Black Non-Hispanic Patients With Head and Neck Squamous Cell Cancer Have the Worst Survival Outcomes.

In this population study, we compared head and neck cancer (HNC) prognosis and risk factors in 2 underserved minority groups (Hispanic and Black non-Hispanic patients) with those in other racial/ethnicity groups. In this SEER-Medicare database study in patients with HNC diagnosed in 2006 through 2015, we evaluated cancer-specific survival (CSS) between different racial/ethnic cohorts as the main outcome. Patient demographics, tumor factors, socioeconomic status, and treatments were analyzed in relation to the primary outcomes between racial/ethnic groups. Black non-Hispanic patients had significantly worse CSS than all other racial/ethnic groups, including Hispanic patients, in unadjusted univariate analysis (Black non-Hispanic patients: hazard ratio, 1.48; 95% CI, 1.33-1.65; Hispanic patients: hazard ratio, 1.12; 95% CI, 0.99-1.28). To investigate the association of several variables with CSS, data were stratified for multivariate analysis using forward Cox regression. This identified socioeconomic status, cancer stage, and receipt of treatment as predictive factors for the survival differences. Black non-Hispanic patients were most likely to present at a later stage (odds ratio, 1.62; 95% CI, 1.38-1.90) and to receive less treatment (odds ratio, 0.67; 95% CI, 0.55-0.81). Unmarried status, high poverty areas, increased emergency department visits, and receipt of healthcare at non-NCI/nonteaching hospitals also significantly impacted stage and treatment. Black non-Hispanic patients have a worse HNC prognosis than patients in all other racial/ethnic groups, including Hispanic patients. Modifiable risk factors include access to nonemergent care and prevention measures, such as tobacco cessation; presence of social support; communication barriers; and access to tertiary centers for appropriate treatment of their cancers.

Identifying potential prognostic biomarkers in head and neck cancer based on the analysis of microRNA expression profiles in TCGA database.

The present study aimed to identify sensitive, specific and independent prognostic biomarkers in head and neck cancer (HNC) based on microRNA expression profiles and other high‑throughput sequencing data in The Cancer Genome Atlas (TCGA) database. Identification of such prognostic biomarkers could provide insight into HNC diagnosis and treatment. The differential expression profiles of microRNAs between HNC tissues and adjacent cancer tissues in the TCGA database were analyzed (log fold‑change >2; P<0.01). Univariate and multivariate Cox regression analyses of the differentially expressed microRNAs were performed to determine those significantly related to the survival of patients with HNC. The identified microRNAs were verified by survival and receiver operating characteristic curve analyses. To better predict prognosis, a combined prognostic model (risk equation) was established based on the risk coefficient of each microRNA, calculated by a multivariate Cox regression analysis, and the risk score was calculated. To explore the signaling pathways related to prognosis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on the differentially expressed genes between the high‑risk and low‑risk groups, grouped according to the median risk score. A total of 89 differentially expressed microRNAs between HNC and adjacent cancer tissues were screened, 11 of which were identified as risk factors related to HNC survival by the univariate Cox regression analysis (P<0.05). The multivariate Cox regression analysis showed that three of the 11 microRNAs, hsa‑miR‑99a, hsa‑miR‑499a and hsa‑miR‑1911 (all P<0.01), were identified as independent risk factors significantly related to patient survival. The risk equation used was as follows: Risk score=(‑0.1597xhsa‑miR‑99a) + (0.1871 x hsa‑miR‑499a) + (0.1033 x hsa‑miR‑1911). KEGG and GO analyses showed that the JAK‑STAT signaling pathway and some metabolic pathways were associated with HNC prognosis. The present study suggested that hsa‑miR‑99a, hsa‑miR‑499a and hsa‑miR‑1911 may serve as potential prognostic biomarkers in HNC.

Diabetes and its Potential Impact on Head and Neck Oncogenesis.

In recent years, the incidence of diabetes mellitus and cancer has increased sharply; indeed, these have become the two most important diseases threatening health and survival. Head and neck (HN) tumors are the sixth most common malignancies in humans. Numerous studies have shown that there are many common risk factors for diabetes mellitus and HN squamous cell carcinoma, including advanced age, poor diet and lifestyle, and environmental factors. However, the mechanism linking the two diseases has not been identified. A number of studies have shown that diabetes affects the development, metastasis, and prognosis of HN cancer, potentially through the associated hyperglycemia, hyperinsulinemia and insulin resistance, or chronic inflammation. More recent studies show that metformin, the first-line drug for the treatment of type 2 diabetes, can significantly reduce the risk of HN tumor development and reduce mortality in diabetic patients. Here, we review recent progress in the study of the relationship between diabetes mellitus and HN carcinogenesis, and its potential mechanisms, in order to provide a scientific basis for the early diagnosis and effective treatment of these diseases.

Prognostic Value of miRNAs in Head and Neck Cancers: A Comprehensive Systematic and Meta-Analysis

Head and Neck Cancer (HNC) is the sixth most common type of cancer across the globe, with more than 300,000 deaths each year, globally. However, there are currently no standardised molecular markers that assist in determining HNC prognosis. The literature for this systematic review and meta-analysis were sourced from multiple bibliographic databases. This review followed PRISMA guidelines. The Hazard Ratio (HR) was selected as the effect size metric to independently assess overall survival (OS), disease-free survival (DFS), and prognosis. Subgroup analysis was performed for individual highly represented miRNA. A total of 6843 patients across 50 studies were included in the systematic review and 34 studies were included in the meta-analysis. Studies across 12 countries were assessed, with China representing 36.7% of all included studies. The analysis of the survival endpoints of OS and DFS were conducted separately, with the overall pooled effect size (HR) for each being 1.825 (95% CI 1.527–2.181; p < 0.05) and 2.596 (95% CI 1.917–3.515; p < 0.05), respectively. Subgroup analysis was conducted for impact of miR-21, 200b, 155, 18a, 34c-5p, 125b, 20a and 375 on OS, and miR-21 and 34a on DFS. The pooled results were found to be statistically significant for both OS and DFS. The meta-analysis indicated that miRNA alterations can account for an 82.5% decrease in OS probability and a 159.6% decrease in DFS probability. These results indicate that miRNAs have potential clinical value as prognostic biomarkers in HNC, with miR-21, 125b, 34c-5p and 18a, in particular, showing great potential as prognostic molecular markers. Further large scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

Systematic analysis of differentially methylated expressed genes and site-specific methylation as potential prognostic markers in head and neck cancer.

Head and neck cancer (HNC) remains one of the most malignant tumors with a significantly high mortality. DNA methylation exerts a vital role in the prognosis of HNC. In this study, we try to screen abnormal differential methylation genes (DMGs) and pathways in Head–Neck Squamous Cell Carcinoma via integral bioinformatics analysis. Data of gene expression microarrays and gene methylation microarrays were obtained from the Cancer Genome Atlas database. Aberrant DMGs were identified by the R Limma package. We conducted the Cox regression analysis to select the prognostic aberrant DMGs and site‐specific methylation. Five aberrant DMGs were recognized that significantly correlated with overall survival. The prognostic model was constructed based on five DMGs (PAX9, STK33, GPR150, INSM1, and EPHX3). The five DMG models acted as prognostic biomarkers for HNC. The area under the curve based on the five DMGs predicting 5‐year survival is 0.665. Moreover, the correlation between the DMGs/site‐specific methylation and gene expression was also explored. The findings demonstrated that the five DMGs can be used as independent prognostic biomarkers for predicting the prognosis of patients with HNC. Our study might lay the groundwork for further mechanism exploration in HNC and may help identify diagnostic biomarkers for early stage HNC.

The Influence of Prediagnosis Alcohol Consumption and the Polymorphisms of Ethanol-Metabolizing Genes on the Survival of Head and Neck Cancer Patients.

Although alcohol drinking is an established risk factor of head and neck cancer (HNC), less is known about its role in the prognosis of HNC. The current study investigated the association between pretreatment alcohol consumption and the overall survival (OS) of HNC patients. Cox proportional hazards models were performed to evaluate the association between prediagnosis alcohol drinking and the OS of HNC patients. In addition, the influence of the polymorphisms of two ethanol-metabolizing genes, ADH1B and ALDH2, on this relationship was also evaluated. The results showed a significant positive dose-response relationship between prediagnosis alcohol use and worse OS of HNC patients. This association was more significant for oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer than for oral cancer. The association between alcohol use and the poorer OS of HNC patients was mainly through its association with a higher stage of HNC at diagnosis. The worst OS associated with alcohol use was observed among HNC patients with the fast ADH1B and the slow/nonfunctional ALDH2 genotype combination. Our analysis showed a significant positive dose-response relationship between prediagnosis alcohol use and a worse OS of HNC. This association was mainly due to the higher stage of HNC among alcohol drinkers. In addition, the polymorphisms of the ethanol-metabolizing genes, ADH1B and ALDH2, modified the relationship between prediagnosis alcohol use and the OS of HNC patients. Prediagnosis alcohol use may be a prognostic indicator of HNC.

The high-sensitivity modified Glasgow prognostic score is superior to the modified Glasgow prognostic score as a prognostic predictor for head and neck cancer.

BackgroundThere is increasing evidence that the inflammatory indices of modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) play important roles in predicting the survival in many cancer; however, evidence supporting such an association in head and neck cancer (HNC) is scarce.Materials and MethodsWe evaluated the impact of the mGPS and HS-mGPS on the overall survival (OS) in 129 patients with HNC treated at Aichi Cancer Center Central Hospital from 2012-2013. The mGPS was calculated as follows: mGPS of 0, C-reactive protein (CRP) ≤1.0 mg/dl; 1, CRP >1.0 mg/dl; 2, CRP>1.0 mg/dl and albumin <3.5 mg/dl. Regarding the HS-mGPS, the CRP threshold level was set as 0.3 mg/dl. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models after adjusting for potential confounders.ResultsThe prognosis of HNC worsened significantly as both the mGPS and HS-mGPS increased in a univariate analysis. After adjusting for covariates, the HS-mGPS was significantly associated with the OS (adjusted HR for HS-mGPS of 2 compared to an HS-mGPS of 0 [HRscore2-0] 3.14 [95% CI: 1.23-8.07], Ptrend < 0.001), while the mGPS was suggested to be associated with the survival (HRscore2-0 2.37 [95% CI:0.89-6.33], Ptrend = 0.145). Even after stratification by clinical covariates, these associations persisted.ConclusionWe conclude that the HS-mGPS is useful as an independent prognostic factor in HNC.

1104P - An insight on head and neck cancer management in China

Background: As no Chinese data has evaluated the oncologists’ strategy for treatment and management of the head and neck cancer (HNC), this survey investigated Chinese oncologists’ treatment strategy in HNC. Methods: This survey was conducted during October 2017 to January 2018 in 100 randomly selected tertiary Chinese hospitals from 21 cities. The plan was to include 300 non-randomly selected Chinese oncologists to know their responses on HNC. The investigating stages included: development of a questionnaire after consulting 9 experts in HNC; execution of a pre-test by 40 oncologists from 5 cities; reliability and validity evaluation followed by finalisation of the questionnaire; and conduct of formal investigation with oncologists. Results for all evaluations were presented as percentages. Results: Of the 296 questionnaires received, 272 were considered valid. Among valid respondents, 65.1% oncologists reported nasopharyngeal carcinoma as the most common HNC, followed by laryngeal/hypopharyngeal (22.1%) carcinoma. 71.3% oncologists acknowledged having a multidisciplinary team for HNC treatment in their hospitals. Prescribed regimens for recurrent/metastatic HNC included taxane + platinum (TP), taxane-cisplatin-5fluorouracil (TFP), PF, TF and others (45.2%, 27.9%, 21%, 2.2% and 3.7%). Oncologists (77.6%) add target therapy to chemotherapy as the first line therapy in recurrent/metastatic cancer. For locally advanced HNC, anti-EGFR would be preferred by 84.2% oncologists. 39.0% oncologists reported considering inclusion of targeted therapy at combined radical radiotherapy and chemotherapy stage. HPV was believed to be associated with HNC prognosis by 72.0% oncologists; 1.9% oncologists disagreed and 26.1% were unsure. HPV testing rate was 67.3%. The reasons for not testing HPV were immature technical conditions (41.2%), no impact on treatment (40.8%), no consent by patients (25.0%) and low HPV incidence in Chinese HNC patients (18.01%). Conclusions: In conclusion, oncologists in China have not fully followed international guidelines of HNC which might be due to practical considerations. These findings will provide future education for HNC management. Legal entity responsible for the study: China Medical University Funding: Merck Serono Co. Ltd, Beijing, China. Disclosure: All authors have declared no conflicts of interest.

1087P - Head and neck cancer (HNC) and synchronic lung cancer: Impact of the lung cancer on the management and prognosis of these patients. Data from the SYNCHRON GFPC 15-04 Study

Background: Management of synchronous head and neck and lung cancer is almost difficult. The aim of this observational study was to describe the impact of the lung cancer on the management and prognosis of HNC. Methods: Inclusion criteria were: consecutive patients diagnosed between January 2011 and December 2015 in 19 French centers with HNC and synchronous lung cancer (all stages). We describe: clinical characteristics, management and outcomes. Patient characteristics and treatment information was analyzed descriptively. Kaplan-Meier estimation was used to assess median overall survival. Results: The study included 132 patients: men: 83%; 63,7 years old, current smokers: 59,8%; performans status: 0 and 1 for 22% and 66% of the patients respectively; high rate of comorbidities: cardiovascular: 63%, COPD: 33%. Main histology for HNC was squamous: 98%, (in oral cavity: 24%, oropharyngeal: 26%, hypo-pharyngeal: 22% and laryngeal: 28%) T classification was T1, T2, T3 and T4 in 16%, 24%, 28% and 18% of cases respectively, and N classification was N0, N1, N2, N3, for 36%, 18%, 20% and 8% of cases respectively. The main treatment was surgery, 37,1%, and chemo-radiotherapy, 35,6%. The diagnosis of lung cancer impacts the HNC management in 38% of the cases. Median delay between HNC and first day treatment was 54 days. HNC progressive free survival rate was 68% at 2 years. Lung cancers were mostly localized (stages I: 46%, stages II: 10%), squamous: 39%, or adeno-carcinomas: 39%. Main treatments were surgery: 29%, mainly lobectomy, radiotherapy: 13%, radio-chemotherapy: 14% and chemotherapy alone: 35%. Seven patients didn’t receive active treatment. Median delay of treatment was 82,3 days. Lung cancer progressive free survival rate was 35% at 2 years. OS was 40% at 2 years, better for stage I - II lung cancers (55%). Conclusions: Synchronous lung cancer at HNC diagnosis significantly impacts the management and outcomes of HNC. Specific recommendations and multidisciplinary approach should be elaborate to improve the management of these patients. Legal entity responsible for the study: Groupe Français de Pneumo-cancérologie Funding: Boringer Pierre Fabre Disclosure: All authors have declared no conflicts of interest.