Risk Of Head And Neck Squamous Cell Carcinoma Research Articles

Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma.

This study aimed to investigate the impact of single-nucleotide polymorphisms (SNPs) in the CD44 gene, specifically in the 3'UTR region (rs13347) and intronic region (rs187115), on the cell surface expression of CD44 protein and the risk of development of head and neck squamous cell carcinoma (HNSCC). The study involved analysis of 85 samples and 85 healthy controls. Immunohistochemistry (IHC) and flow cytometry were used to assess cell surface protein expression using CD44 antibody. DNA from formalin-fixed paraffin-embedded tissue sections was isolated and amplified using targeted primers. Sanger sequencing of the resultant amplified products was performed to determine the genotypes of the CD44 rs13347 and rs187115 SNPs. GTEx and RegulomeDB were queried to evaluate the genotypic effects of these variants on target gene expression and regulation. A comparison between patients with HNSCC and healthy controls revealed a significant association between CD44 rs13347 and an increased risk of HNSCC in all the analyzed models, especially the TT genotype showed a significantly higher risk with an odds ratio of 8.69 (95% CI, 2.35 to 32.09; P = .0003). However, no significant association was found between CD44 rs187115 and HNSCC in any of the models analyzed (all P > .05). Other notable findings included significant associations between CD44 rs13347 genotype and age (P = .031), number of CD44-positive tumor cells (P = .049), CD44 staining intensity (SI; P = .039), and CD44 immunoreactivity score (IRS) status (P = .019). The T allele and homozygous TT genotype of CD44 rs13347 SNP were associated with increased susceptibility to HNSCC and decreased proportion of CD44-positive tumor cells, low SI, and reduced IRS.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive detection of head and neck squamous cell carcinomas.

e18054 Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. The mortality from HNSCC is closely linked to stage. However, the majority of HNSCC patients were diagnosed at an advanced stage. Therefore, a non-invasive assay for the early detection of HNSCCs is highly desirable for reducing the associated mortality. Methods: We collected a study cohort of 281 participants including 140 pathologically confirmed with head and neck squamous cell carcinomas (HNSCCs) and 141 with non-cancerous conditions. A plasma sample was collected from each participant along with general health screening examinations before any invasive examinations. We performed low-pass whole-genome sequencing with plasma samples and profiled three types of cell-free DNA (cfDNA) characteristics, fragment size pattern (FSP), copy number variation (CNV), and single nucleotide substitution (SNS). We developed an ensemble model with these differential profiles to identify HNSCC patients from non-cancer individuals. We further collected a validation cohort consisting of 90 HNSCC patients and 95 non-cancer individuals to validate the cfDNA-based assay. Results: The liquid biopsy assay that incorporated three types of cfDNA characteristics was able to identify HNSCC patients from non-cancer individuals at an AUROC of 0.989 in the study cohort and 0.984 in the validation cohort. At a specificity of 95.7% (135/141), it achieved a sensitivity of 95.7% (134/140) in the study cohort. With this threshold (0.580), in the validation cohort, 93.7% (89/95) of non-cancer individuals and 93.3% (84/90) of HNSCC patients were correctly identified. Specifically, the sensitivities in early stage (I&II) HNSCCs were 94.5 % (52/55) and 87.5% (28/32) in the study and validation cohort, respectively. Of note, the inferred probabilities of cancer showed consistent trends to increase with pathological stages in both cohorts (P=0.032 and 0.047, respectively). On the contrary, the differentiation grades and sub-locations did not significantly affect the performance of the assay. Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify HNSCCs from non-cancerous conditions. As a cost-effective non-invasive approach, it may be conveniently incorporated into annual general physical examinations to provide supplementary information about the risk of HNSCCs.

77 Emerging strategies for head & neck cancer prevention

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies mostly involving the oral cavity, oropharynx, hypopharynx, and larynx. All together they represent the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In this context, the risk of second primary tumors in the field of cancerization is high. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer survival.Based on this epidemiological facts, different strategies involving primary, secondary and tertiary prevention will be discussed. For prevention of HPV-positive HNSCC, emphasis will be given to vaccination strategies and novel diagnostic biomarkers for early detection. HPV-negative HNSCC are mostly represented by oral cavity cancers. In this particular context, a Working Group of international experts was convened by the International Agency for Research on Cancer (IARC) to review and assess all available evidence on the effectiveness of primary and secondary preventive interventions in reducing the incidence of and mortality from oral cancer. Available evidence will be summarized. Finally, we will address the challenge of unmet oral cancer prevention in the context of oral potentially malignant disorders (OPMD) in terms of oral cancer risk assessment and pharmacological interception approachs.In conclusion, a lot remains to be done to improve the prevention of HNSCC but significant opportunities exist that will hopefully allow in the near future to significantly decrease its morbidity, mortality, and profound impact on patient's quality of life.

Analysis of HLA-G 14 bp Insertion/Deletion Polymorphism and HLA-G, ILT2 and ILT4 Expression in Head and Neck Squamous Cell Carcinoma Patients.

HLA-G is the checkpoint molecule involved in the suppression of the immune response. Increased expression of HLA-G and its ILTs receptors have been correlated with tumor progression in various cancer types. In head and neck squamous cell carcinoma (HNSCC) tumors, the effect of HLA-G, ILT2 and ILT4 expression on cancer development has to be explained. The 34 HNSCC patients and 98 controls were genotyped for the HLA-G 14 bp ins/del polymorphism. In HNSCC lesions, HLA-G, ILT2 and ILT4 mRNA expression was analysed using real-time PCR. The association between HLA-G, ILT2 and ILT4 mRNA expression and clinical variables (age at onset, TNM staging system and p16 positivity) was also evaluated. No genetic association between the HLA-G 14 bp ins/del and HNSCC risk was detected (p > 0.05). However, in the non-metastatic HNSCC group, a significantly higher HLA-G mRNA expression was noted in tumors in the T4 stage compared to those in the T1 and T2 stages (p = 0.0289). ILT2 mRNA expression was significantly increased in non-metastatic vs. metastatic tumors (p = 0.0269). Furthermore, a significantly higher ILT4 mRNA expression was noted in tumors in the T1+T2 stage compared to those in the T3 stage (p = 0.0495). Our results suggest that the HLA-G molecule creates an immunological microenvironment involved in HNSCC development.

DYNC1I1 acts as a promising prognostic biomarker and is correlated with immune infiltration in head and neck squamous cell carcinoma

Background/purposeDynein Cytoplasmic 1 Intermediate Chain 1 (DYNC1I1) is a crucial cytoplasmic dynein binding component, its high expression levels are associated with malignant progression and poor survival in different types of cancer; however, the oncogenic role of DYNC1I1 in Head and neck squamous cell carcinomas (HNSCC) remains to be elucidated. In our present study, we aimed to explore the potential role of DYNC1I1 expression in the tumorigenesis of HNSCC and the shaping of the immune microenvironment. Materials and methodsThe expression levels of DYNC1I1 were analyzed in The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset, and then real-time quantitative polymerase chain reaction (RT-qPCR) was used to validate the DYNC1I1 expression in oral squamous cell carcinoma (OSCC) tumor samples, one of the major types of HNSCC. The functional pathway, tumor immune infiltration, and gene expression correlation for DYNC1I1 were performed using different bioinformatic tools. ResultsWe found that the expression of DYNC1I1 was significantly increased in HNSCC and was a predictor of poor survival. The DYNC1I1 high expression has also been associated with an increased risk of HPV-negative HNSCC and decreased immune cell infiltration. Functional enrichment analysis identified that DYNC1I1 is involved in several important signaling pathways that contribute to the cancer cell's survival and proliferation. ConclusionOur findings indicate that DYNC1I1 plays an important role in the tumorigenesis of HNSCC, and could be a promising prognostic biomarker for HNSCC diagnosis and treatment.

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6months. Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. UMIN000001676.

Impact of Alcohol Dehydrogenase 7 Polymorphism and Alcohol Consumption on Risk of Head and Neck Squamous Cell Carcinoma: A Korean Case-Control Study.

Head and neck squamous cell carcinoma (HNSCC) is closely associated with alcohol consumption and individual genetic susceptibility, such as single nucleotide polymorphism (SNP) of alcohol dehydrogenase (ADH). This study aimed to investigate the association of ADH7 SNPs with the risk of HNSCC. We analyzed ADH7 rs1573496C>G, rs3737482T>C, rs1154460G>A, and rs284787T>C SNPs in 250 patients with HNSCC and 322 controls in the Korean populations. Genotyping was conducted using the TaqMan assay. Linkage disequilibrium and haplotypes were analyzed. The odds ratios (OR) and 95% confidence intervals (CI) of the CT and CC genotypes of ADH7 rs3737482T>C were 0.48 (0.29-0.78) and 0.69 (0.49-0.96), indicating a significantly decreased risk. In SNP of rs1154460G>A, the OR and 95% CI of the AA genotype was 1.63 (1.11-2.40), showing a significant increase in the risk. Furthermore, SNPs of ADH7 rs3737482T>C and ADH7 rs1154460G>A exhibit synergistic interactions with alcohol composition on the risk of HNSCC. None of the haplotypes were associated with the risk of HNSCC. ADH7 rs3737482T>C and rs1154460G>A SNPs are associated with the risk of development of HNSCC in Koreans. They could serve as molecular biological markers to screen high-risk groups for HNSCC.

Unsupervised Hierarchical Clustering of Head and Neck Cancer Patients by Pre-Treatment Plasma Metabolomics Creates Prognostic Metabolic Subtypes.

There is growing evidence that the metabolism is deeply intertwined with head and neck squamous cell carcinoma (HNSCC) progression and survival but little is known about circulating metabolite patterns and their clinical potential. We performed unsupervised hierarchical clustering of 209 HNSCC patients via pre-treatment plasma metabolomics to identify metabolic subtypes. We annotated the subtypes via pathway enrichment analysis and investigated their association with overall and progression-free survival. We stratified the survival analyses by smoking history. High-resolution metabolomics extracted 186 laboratory-confirmed metabolites. The optimal model created two patient clusters, of subtypes A and B, corresponding to 41% and 59% of the study population, respectively. Fatty acid biosynthesis, acetyl-CoA transport, arginine and proline, as well as the galactose metabolism pathways differentiated the subtypes. Relative to subtype B, subtype A patients experienced significantly worse overall and progression-free survival but only among ever-smokers. The estimated three-year overall survival was 61% for subtype A and 86% for subtype B; log-rank p = 0.001. The association with survival was independent of HPV status and other HNSCC risk factors (adjusted hazard ratio = 3.58, 95% CI: 1.46, 8.78). Our findings suggest that a non-invasive metabolomic biomarker would add crucial information to clinical risk stratification and raise translational research questions about testing such a biomarker in clinical trials.

Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths. In the developing world, the incidence of HNSCC is growing with increasing consumption of tobacco (smoked or chewed), alcohol, and areca nut (betel quid). Alcohol and tobacco have a synergistic effect, with the heavy consumption of both increasing HNSCC risk 40-fold. In developed nations, HPV-related HNSCC surpasses tobacco- and alcohol-related disease. HPV-related HNSCC more commonly affects the oropharynx, hypopharynx, and larynx than the oral cavity, and is associated with a significantly longer median survival (130 months vs. 20 months). Discrepancies in etiology as well as disparities in lifestyle choices and access to healthcare may account for the greater incidence and poorer survival of HNSCC among minority and lower-socioeconomic-status communities in developed nations. Pharmacotherapy and counseling together have been shown to be effective in promoting smoking and alcohol cessation. Education on cancer risk and community engagement have reduced areca nut consumption in Asia as well as in diaspora communities. HPV vaccination, starting at age 11-12 for both sexes, has been shown to reduce the prevalence of high-risk HPV serologies and prevent pre-cancerous lesions of the cervix, vagina, and vulva. As of 2020, 58.6% of eligible adolescents in the US have received the full two-vaccine series. Increased adoption of vaccination, education on safe sex practices, and routine visual oral screening for high-risk patients would curb growing HNSCC incidence in developed nations.

Association between sexual behaviour and head and neck cancer in the French West Indies: a case-control study based on an Afro-Caribbean population

BackgroundWorldwide, a significant proportion of head and neck cancers is attributed to the Human papillomavirus (HPV). It is imperative that we acquire a solid understanding of the natural history of this virus in head and neck squamous cell carcinoma (HNSCC) development. Our objective was to investigate the role of sexual behaviour in the occurrence of HNSCC in the French West Indies. Additionally, we evaluated the association of high risk of HPV (Hr-HPV) with sexual behaviour in risk of cancer.MethodsWe conducted a population-based case-control study (145 cases and 405 controls). We used logistic regression models to estimate adjusted odds-ratios (OR), and their 95% confidence intervals (CI).ResultsCompared to persons who never practiced oral sex, those who practiced at least occasionally had a lower HNSCC risk. First sexual intercourse after the age of 18 year was associated with a 50% reduction of HNSCC risk, compared to those who began before 15 years. HNSCC risk was significantly reduced by 60% among persons who used condoms at least occasionally. The associations for ever condom use and oral sex were accentuated following the adjustment for high-risk HPV (Hr-HPV). Oral Hr-HPV was associated with several sexual behaviour variables among HNSCC cases. However, none of these variables were significantly associated with oral HPV infections in the population controls.ConclusionFirst intercourse after 18 years, short time interval since last intercourse and ever condom use were inversely associated with HNSCC independently of oral Hr-HPV infection. Sources of transmission other than sexual contact and the interaction between HPV and HIV could also play a role in HNSCC etiology.

'Toxic Masculinity': What Is Known about the Role of Androgen Receptors in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC), the most prevalent cancer in the head and neck region, develops from the mucosal epithelium of the upper aerodigestive tract. Its development directly correlates with alcohol and/or tobacco consumption and infection with human papillomavirus. Interestingly, the relative risk for HNSCC is up to five times higher in males, so it is considered that the endocrine microenvironment is another risk factor. A gender-specific risk for HNSCC suggests either the existence of specific risk factors that affect only males or that females have defensive hormonal and metabolic features. In this review, we summarized the current knowledge about the role of both nuclear and membrane androgen receptors (nAR and mARs, respectively) in HNSCC. As expected, the significance of nAR is much better known; it was shown that increased nAR expression was observed in HNSCC, while treatment with dihydrotestosterone increased proliferation, migration, and invasion of HNSCC cells. For only three out of five currently known mARs-TRPM8, CaV1.2, and OXER1-it was shown either their increased expression in various types of HNSCC or that their increased activity enhanced the migration and invasion of HNSCC cells. The primary treatments for HNSCC are surgery and radiotherapy, but targeted immunotherapies are on the rise. On the other hand, given the evidence of elevated nAR expression in HNSCC, this receptor represents a potential target for antiandrogen therapy. Moreover, there is still plenty of room for further examination of mARs' role in HNSCC diagnosis, prognosis, and treatment.

Low level of BRCA2 in peripheral blood lymphocytes is associated with an increased risk for head and neck squamous cell carcinoma (HNSCC) in a population of North-East India: a case-control study.

We investigated the role of DNA repair proteins breast cancer susceptibility 2 (BRCA2), xeroderma pigmentosum group D (XPD) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) in determining the risk for head and neck squamous cell cancer (HNSCC) in a case-control study from North-East India. Expression of BRCA2, XPD and APE1 genes in the matched tumour, normal adjacent tissue (NAT) and blood of 12 HNSCC patients and blood of 8 age- and gender-matched controls was determined by quantitative real-time PCR. Results were validated by expression analysis of the corresponding proteins in the peripheral blood lymphocytes (PBLs) of 228 subjects (106 patients and 122 controls) by a slot-blot immunoassay. Expression of the BRCA2 and XPD genes in tumour tissue of HNSCC patients declined progressively as the cancer stage advanced, was reverse that of the NAT, but was mirrored by the expression in the blood. BRCA2 and XPD proteins were significantly (p < 0.0001) downregulated in the PBL of HNSCC patients to 71% and 77% the levels in controls, showing significant negative correlation with HNSCC stage (Spearman correlation coefficient (r s) of -0.9060, p < 0.0001 for BRCA2; r s of -0.8008, p < 0.01 for XPD). On the contrary, APE1 was significantly upregulated in PBL of HNSCC patients to 1.47 fold the level in controls, showing significant positive correlation with HNSCC stage (r s of 0.7023, p < 0.01). Classification and regression tree analyses predicted low levels of BRCA2 protein in PBL as the single most important risk factor for HNSCC, independent of gender. Smokers above 36 years of age with low level of BRCA2 appeared to exhibit a 1.78-fold increased risk for HNSCC (with a 1.78-fold increased risk for HNSCC (OR = 1.78, 95% confidence interval (CI) = 0.33-9.52) though this risk was not significant statistically. Similarly, low levels of BRCA2 appeared to indicate a moderate, but non-significant risk for HNSCC in non-smokers aged between 36 and 56 years (OR = 1.15, 95% CI = 0.21-6.37). Low level of BRCA2 protein in the peripheral blood indicates increased risk for HNSCC.

Gene polymorphisms and risk of head and neck squamous cell carcinoma: a systematic review.

Exposure to the same environmental factors in different people have resulted in different susceptibility to head and neck squamous cell carcinoma (HNSCC), which suggests genetic variation may be a risk factor for the development of HNSCC. So, the aim was to review literatures on the association between gene polymorphisms and risk of HNSCCs. This systematic review included all articles on the impact of gene polymorphisms on risk and susceptibility to HNSCC published till September 2021 using PubMed, Web of science, SCOPUS, Google Scholar and Cochrane library databases. Of 1163 initial searched articles, 77 articles were eligible to include in this review. Studies were categorized based on gene functions. In each category, studied gene polymorphisms related to growth control genes, cell cycle control, apoptosis, DNA repair genes, carcinogen-metabolizing enzymes, alcohol-metabolizing genes, antioxidant gene, inflammatory cytokine, transcription factor, tumor immunity, folate metabolism, and tumor suppressor gene were discussed separately. Among the polymorphisms that are often significantly associated with HNSCC risk are: GSTM1 null, GSTT1 null, CYP2D6 *4, XRCC1 Arg194Trp and Arg399Gln, ERCC1 C8092A, XPD Lys751Gln, XRCC3 Thr241Met, P53 codon 72 and MTHFR C677T polymorphisms. Varied and contradictory results have been reported in different studies regarding the association of gene polymorphisms with HNSCC risk. To conclude about this association and to overcome these contradictions, it is necessary to use the results of existing meta-analyses or to perform new or updated meta-analyses.

Assessment of dietary pattern and serum levels of vitamins A, C, and E in patients with head and neck squamous cell carcinoma (HNSCC): A case-control study

Background: The importance of dietary pattern and vitamins in the incidence of cancers has been demonstrated in many studies. As there are cultural differences and various dietary patterns in different countries, the results of other studies are not necessarily applicable to our society. This study aimed to evaluate the role of some vitamins and dietary patterns in developing head and neck cancer. Methods: Dietary pattern and serum levels of vitamins in 39 patients with head and neck squamous cell carcinoma (HNSCC) were compared to 37 healthy individuals. A native questionnaire was used to obtain the dietary pattern. The existence of a significant relationship between serum levels of vitamins and dietary pattern with the risk of HNSCC was assessed. The independent t test, chi-square and exact Fisher’s test were employed for statistical analysis. Results: The mean serum levels of these vitamins in the case group were significantly lower as compared to the control subjects (P&lt;0.005). Two dominant eating patterns were identified, and after adjusting for confounding factors such as age, education, physical activity, body mass index (BMI), and place of residence, it was found that people with unhealthy dietary patterns were 6.55 times more likely to develop cancer than people with a healthy diet. Conclusion: Lower serum levels of vitamins C and E are associated with an increased risk of HNSCC. Unhealthy dietary patterns also increase the risk of developing this cancer.

The XRCC1 Arg194Trp polymorphism was associated with the risk of head and neck squamous cell carcinoma development: Results from a systematic review and meta-analysis.

The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. Thirty three studies consisting of 14282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR = 1.182, 95%CI = 1.015-1.377, P = 0.032; homozygous model: OR = 1.274, 95%CI = 0.940-1.727, P = 0.119; dominant model: OR = 1.194, 95%CI = 1.027-1.388, P = 0.021; recessive model: OR = 1.181, 95%CI = 0.885-1.576, P = 0.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. The X-ray repair cross complementing group 1 (XRCC1) is a DNA repair gene. Various studies have examined the association between XRCC1 Arg194Trp polymorphism and head and neck squamous cell carcinoma (HNSCC) susceptibility with contradictory results. So, this systematic review and meta-analysis aimed to assess whether variants of this polymorphism increase the HNSCC risk or not. A systematic search of the literatures published till April 2022 was conducted using Google Scholar, Scopus, PubMed, Web of Science, Cochrane Library and Embase databases. The heterogeneity was assessed with the I-Square statistic. A random effects model or fixed effects model was used to analyze the data. Data were reported by odds ratio (OR) and 95% confidence interval (CI). The p value was considered significant if p < .05. Thirty three studies consisting of 14 282 subjects (6012 cases and 8270 controls) were included in this meta-analysis. Variants of XRCC1 Arg194Trp polymorphism were associated with increased HNSCC risk and the associations were significant based on heterozygous and dominant models (heterozygous model: OR=1.182, 95%CI=1.015-1.377, p=.032; homozygous model: OR=1.274, 95%CI=0.940-1.727, p=.119; dominant model: OR=1.194, 95%CI=1.027-1.388, p=.021; recessive model: OR=1.181, 95%CI=0.885-1.576, p=.119). There were significant associations between variants of this polymorphism and HNSCC risk based on Asian ethnicity under dominant model, hospital control source under different genetic models, PCR-RFLP genotyping method under dominant model and oral cavity tumor site under heterozygous and dominant models. Variants of XRCC1 Arg194Trp polymorphism were significantly associated with increased risk of HNSCC development based on heterozygous and dominant genetic models.

Men with Crohn’s disease may have an increased risk for head and neck squamous cell carcinoma — a nationwide register study

ObjectiveOur goal was to study inflammatory bowel disease (IBD) patients’ risk of head and neck squamous cell carcinoma (HNSCC), compared to general population.Materials and methodsWe performed a retrospective nationwide register-based study of Finnish individuals diagnosed with IBD between the years 1995 and 2015. The standardized incidence ratio (SIR) of HNSCC was calculated by comparing the cohort’s complementary age-year-sex-person-year incidence to that of the whole Finnish population.ResultsAbout 70,567 patients were diagnosed with IBD (Crohn’s disease or ulcerative colitis). Later, 89 of them were diagnosed with HNSCC with mean time of 6.82 years. The incidence of HNSCC was increased in IBD patients compared to the Finnish population expectation (SIR 1.3, 95% CI 1.065–1.614, P = 0.062). When calculating Crohn’s disease and ulcerative colitis separately as well as men and women separately, the incidence was particularly increased for men with Crohn’s disease (SIR 1.951, 95% CI 1.216–2.935, P = 0.025).ConclusionAn increased risk for HNSCC was found in men with Crohn’s disease compared to the Finnish population expectations.Clinical relevanceThis study provides information that would improve follow-up protocols and treatment guidelines of IBD.

M6A RNA methylation regulator-related signatures exhibit good prognosis prediction ability for head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) has become the sixth most common malignant disease worldwide and is associated with high mortality, with an overall 5-year survival rate of less than 50%. Recent studies have demonstrated that aberrantly expressed m6A regulators are involved in multiple biological and pathological processes, including cancers, but the specific mechanisms of m6A regulators in HNSCC are not well elucidated. In this study, we adopted The Cancer Genome Atlas (TCGA)-HNSCC database and performed a consensus clustering analysis to classify the HNSCC samples. Least absolute shrinkage and selection operator (LASSO) regression was applied to construct an m6A signature-based HNSCC risk prediction model. Cell type identification based on estimating relative subsets of RNA transcripts (CIBERSORT) algorithms was adopted to evaluate the immune cell infiltration level in the tumor microenvironment. Based on the expression of m6A regulators in HNSCC, we identified two clusters, cluster 1 (C1) and cluster 2 (C2). C2 showed a better prognosis than C1 and was mainly enriched in the HIPPO, MYC, NOTCH, and NRF signaling pathways. We constructed an m6A signature-based risk score model and classified patients into high- and low-risk score subgroups. The high-risk-score group showed poor clinical characteristics, higher immune infiltration levels, higher chemokine and chemokine receptor expression levels, and lower immune checkpoint gene expression than the low-risk-score subgroup. In conclusion, our comprehensive analysis suggests that the m6A signature-based risk score might function as a good prognostic predictor. Our study may provide novel therapeutic clues and help predict the prognosis of HNSCC.

Combining Phenotypes of Nucleotide Excision Repair Pathway to Predict the Risk of Head and Neck Squamous Cell Carcinomas in a Chinese Population

Background Nucleotide excision repair (NER) is pivotal in the development of smoking-related malignancies. Nine core genes (XPA, XPB, XPC, XPD, XPF, XPG, ERCC1, DDB1, and DDB2) are highly involved in the NER process. We combined two phenotypes of NER pathway (NER protein and NER gene mRNA expression) and evaluated their associations with the risks of the head and neck squamous cell carcinomas (HNSCCs) in a Chinese population. Methods We conducted a case-control study of 337 HNSCC patients and 285 cancer-free controls by measuring the expression levels of nine core NER proteins and NER gene mRNA in cultured peripheral lymphocytes. Results Compared with the controls, cases had statistically significantly lower protein expression levels of XPA (P < 0.001) and lower mRNA expression levels of XPA and XPB (P = 0.005 and 0.001, respectively). After dividing the subjects by controls' medians of expression levels, we found an association between increased risks of HNSCCs and low XPA protein level (Ptrend = 0.031), as well as low mRNA levels of XPA and XPB (Ptrend = 0.024 and 0.001, respectively). Subsequently, we correlated the two phenotypes and found associations between the NER mRNA and protein levels. Finally, the sensitivity of the expanded model with protein and mRNA expression levels, in addition to demographic variables, on HNSCCs risk was significantly improved. Conclusions Combining two phenotypes of NER pathway may be more effective than the model only including one single phenotype for the assessment of risks of HNSCCs.

Impact of single nucleotide polymorphisms and cigarette smoking on cancer risk and survival of patients with head and neck squamous cell carcinoma

Background: Head and neck squamous cell carcinoma (HNSCC) is a disease involving genetic and lifestyle risk factors such as smoking or high-risk papillomavirus (HR-HPV) infections. Objective: This study analyzed 92 single nucleotide polymorphisms (SNPs) associated with smoking and HPV on HNSCC cancer risk and survival among HNSCC patients. Material and methods: Eighty-six HNSCC patients (48 non-smoking and 38 smoking) were consecutively included. Results: Differences were detected in the analysis of survival and SNP genotypes located in the CXCR2 and COMT. Five SNPs in genes PRKDC, TGFb, XRCC1, Cyp2A6 and CTLA4 were found to be different when comparing SNP genotypes in all patients and all controls as a risk of HNSCC. When comparing SNP genotypes among smoking patients and smoking controls, six SNPs in the genes PFR1, IL10, CCL4, IL6, Ku70, and PRF1 were detected. When comparing SNP genotypes, nine SNPs in CHRNA3, PRKDC, CHARNA5, IFN-γ, ESR1, XRCC1, Cyp2A6, CTLA4, and COMT were different in non-smoking patients and non-smoking controls. No association was found between SNP distribution or patient survival and the impact of HR-HPV. Conclusions: The SNPs differed between smokers and non-smokers and could indicate a possible interaction between genetics and smoking. This could play an important role in a better understanding of the pathogenesis of HNSCC.

Risk SNP-mediated LINC01614 upregulation drives head and neck squamous cell carcinoma progression via PI3K/AKT signaling pathway.

As potential biomarkers and therapeutic targets, long noncoding RNAs (lncRNAs) are involved in the tumorigenesis of various tumors. Genetic variation in long noncoding regions can lead to lncRNAdysfunction and even cancer. Nevertheless, studies on the association between lncRNA-associated single-nucleotide polymorphisms (SNPs) and the risk of head and neck squamous cell carcinoma (HNSCC) remain inadequate. Here, we aimed to explore the association between SNPs in LINC01614 and HNSCC risk, and the potential role of LINC01614 in tumorigenesis. In this study, we found that rs16854802 A > G (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.22-1.77, p < 0.001) and rs3113503 G > C (OR = 1.38, 95%CI: 1.15-1.64, p < 0.001) in LINC01614 increased the risk of HNSCC in the Chinese population. Functional bioinformatic analysis and luciferase reporter assay revealed that rs3113503 G > C variant disrupted the binding of miRNA-616-3p to LINC01614, which resulted in the increased expression of LINC01614. Further analysis of the TCGA database demonstrated that the upregulated LINC01614 in HNSCC cancer tissues was associated with poor prognostic in HNSCC patients. In vitro experiments showed that knockdown of LINC01614 inhibited the proliferation, invasion, and migration ability of HNSCC cells. Mechanistically, allele C of rs3113503 in LINC01614 was more effective than allele G in activating the PI3K/AKT signaling pathway. Moreover, the reduced expression of LINC01614 also inhibited the activation of the PI3K/AKT signaling pathway. In summary, our findings revealed that the risk SNP rs3113503 G > C in LINC01614 altered the binding to miR-616-3p, which led to increased LINC01614 expression and promoted HNSCC progression by activating the PI3K/AKT signaling pathway.