Locally advanced buccal mucosa cancer is typically treated with surgery and adjuvant postoperative radiation therapy, which includes concurrent Cisplatin 100 mg/m2 on Day 1, plus 5-Fluorouracil 1000 mg/m2 from Day 1 to 4 every three weeks. Ipsilateral face radiotherapy is a de-escalated treatment that spares the opposite side of the face, enhancing post-treatment chewing function. The availability of electron beam radiotherapy for treating recurrences on the opposite side has increased the use of ipsilateral face radiotherapy. This retrospective study aimed to assess treatment outcomes and patterns of disease recurrence in patients with carcinoma of the buccal mucosa treated with different schedules. We retrospectively reviewed records of 54 patients with a pathological diagnosis of buccal mucosa cancers treated between 2018 and 2023. We extracted patients' demographic, disease, and treatment criteria. Indications for postoperative radiotherapy included a close margin of less than 3 mm and lymph node positivity. The primary tumor (face) and neck were considered separately for radiotherapy treatment. One patient who refused surgery, radiotherapy, and chemotherapy but regularly came for follow-up after receiving Ayurvedic treatment died of the disease after 2 years and 1 month. Fifty-three patients received concurrent chemoradiotherapy with Cisplatin 100 mg/m2 on Day 1, plus 5-Fluorouracil 1000 mg/m2 from Day 1 to 4 every three weeks for three cycles. Postoperative patients were treated with radiotherapy fields covering the face (bilateral or ipsilateral wedged fields) and the whole neck field with central shielding for the initial 44 Gy in 22 fractions over 4.5 weeks followed by a boost dose of 16 Gy to the primary tumor and involved neck. For radical radiotherapy, patients received a similar radiation field but the boost dose delivered was 26 Gy in 13 fractions over 2.5 weeks. For ipsilateral radiotherapy fields, the average face anterior field size was 6 W x 8 cm; the thick edge of the wedge laterally; depth 4 cm and lateral 8 W x 8 cm radiation field with a thick edge of the wedge anteriorly; depth 3 cm. The median dose to high-risk clinical target volume was 60 Gy/30 fractions in postoperative cases. Forty-eight patients received radical radiotherapy with a higher dose (66 Gy/33 fractions to 70 Gy/35 fractions); twenty-eight patients received radiotherapy fields of bilateral face and neck with a central spinal shield of 2 cm. Statistical analysis was conducted at the Community Medicine Department using SPSS software version 21.0. The Chi-square test and Fisher Exact test were applied to compare various groups. Fifty-four patients were analyzed. The median follow-up was 9 months. Surgery consisted of Composite Resection (Commando operation) plus Radical Neck dissection in three (5.5%) patients and non-composite resection surgeries (Wide excision of the lesion plus supra-omohyoid dissection) in nine (16.6%) cases, of which six (50%) cases had lymph node involvement but no patient with positive dissection had extracapsular extension. Tumor thickness by histopathology was found to be between 5 and 15 mm. Sixteen (28.1%) patients failed locally and 11 (20.3%) had lymph node recurrences. One patient (1.8%) with mucoepidermoid cancer had bony metastases at D9, L1, and the pelvis after 4 months of treatment. Death occurred in 12 (20.3%; one due to a non-oncologic cause) out of 54 patients during our study. The majority (88%) of patients in our study are male, aged less than 50 (55%). A KPS of 70/>70 was present in 83.3% of patients. The majority of patients in this study are T3 (37%) and T4a (29.6%). Nodal status of patients included 29.6% N0; 27.7% N1, and 35.1% N2. The majority of patients (57.4%) have well-differentiated carcinoma followed by moderately differentiated carcinoma in 38.8% of patients. The difference in death is non-significant when ipsilateral face + neck radiotherapy is compared to bilateral face + neck radiotherapy by Fisher Exact test (statistical value = 0.1246; p > 0.05, statistically not significant), and in other groups, it could not be compared due to the small number of patients. Our results show the non-inferiority of non-composite resection surgery + bilateral face + neck radiotherapy to non-operative radical radiotherapy (bilateral or ipsilateral face wedged radiotherapy + neck radiotherapy), so the majority of patients can be treated by these modalities of treatment. De-escalation of radiotherapy by the use of ipsilateral face wedged + neck radiotherapy is possible as there is no statistically significant difference in local and nodal relapse when compared to bilateral face + neck radiotherapy, and it results in sparing of the opposite side of the face. Buccal mucosa carcinoma in eastern Uttar Pradesh is a very aggressive disease, with 12 (20.3%; one due to a non-oncologic cause) out of 54 patients dying. Our results are different compared to historical data, possibly due to the use of concurrent Cisplatin + 5-Fluorouracil chemotherapy and the lower number of patients in the composite resection group as the majority of patients were frail and did not consent to composite resection.

Head and neck squamous cell carcinoma (HNSCC) is notorious for poor prognoses, and effective biomarkers are urgently needed for early diagnosis of HNSCC patients. We investigate the role of alkaline ceramidase 1 (ACER1) and its relationship with immune infiltration in HNSCC. The differential expression and clinical prognostic significance of ACER1 in HNSCC patients are explored using bioinformatics methods and verified in human HNSCC samples. Genetic mutation, DNA methylation and drug sensitivity linked with ACER1 are examined. The potential biological function of ACER1 co-expression genes is assessed, and a series of functional assays are performed on ACER1in vitro. The results comprehensively reveal a relationship between ACER1 and immune infiltration in HNSCC patients. ACER1 expression is significantly downregulated in HNSCC tissues and closely correlated with better prognoses for HNSCC patients, and this prognostic significance is determined by distinct clinical characteristics. Genetic alteration and promoter hypomethylation of ACER1 are involved in progression of HNSCC, and ACER1 expression is significantly related to several drug sensitivities. Functional analysis shows that ACER1 co-expression genes are mainly enriched in the sphingolipid signaling pathway associated with inhibition of tumorigenesis, leading to better prognoses for HNSCC patients. In vitro, ACER1 overexpression inhibits proliferation and migration, induces apoptosis, and promotes adhesion of Fadu and SCC9 cells. In addition, high ACER1 expression is closely linked with infiltration levels of immune cells, and strongly associated with biomarkers of immune cells in HNSCC, suggesting the important role of ACER1 in regulating tumor immunity in HNSCC patients. In summary, ACER1 may be a useful indicator for diagnosis and prognosis, and may regulate immune infiltration in HNSCC patients, thus promising targeted immunotherapy for HNSCC.

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study's findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies.

Exosomes are extracellular vesicles found in saliva and other body fluids. These vesicles range in size from 30 to 150 nm and play a crucial role in intercellular communication, transporting different biomolecules, actively targeting cells. These vesicles regulate both physiological and pathological processes within recipient cells. MicroRNAs (miRs) are transported within exosomes and are delivered to target cells where they influence signaling pathways, taking on a crucial regulatory role in oncogenesis; for example, they are implicated in progression and infiltration of various cancers, such as head and neck squamous cell carcinoma (HNSCC).

A systematic literature search based on specific keywords, according to the PRISMA guidelines, was carried out on PubMed, Web of Science, Scopus, and Google Scholar. Only original articles were selected during this review. The risk of bias was assessed by QUADAS-2.

At the end of the selection process 9 articles were included. In these studies, 41 miRs showed differential expression between healthy subjects and patient with HNSCC. The techniques varied among studies for the extraction and analysis of exosomal miRs. We presented also salivary exosomal miRs pathways, to give insights about pathogenetic mechanisms.

Exosomal microRNA are promising biomarkers for HNSCC detection. MiR-10b-5p, miR-486-5p, miR-24-3p, miR-412-3p, and miR-512-3p are the most promising markers applicable to diagnostics, while miR-1307-5p and miR-519c-3p resulted overexpressed and correlated to worse survival outcomes.

Early diagnosis of head and neck cancer can improve therapeutic outcomes but remains a challenge. The blood proteome can comprise a key source of biomarkers that enable the early diagnosis and precision medicine in head and neck cancer, but blood protein biomarkers of head and neck cancer are not well delineated. Here we applied two-sample Mendelian randomization to a GWAS dataset of 1478 blood proteins and large dataset of head and neck cancer cases and controls to identify blood proteome traits associated with head and neck cancer. Multiple two-sample Mendelian randomization (MR) methods were used to assess causal effects of the exposures, including: Inverse-variance weighted (IVW), Mendelian randomization-Egger method, Weight Median method, simple mode, weight mode. Sensitivity analysis was performed by using heterogeneity test, pleiotropy test and one-by-one exclusion test. Multivariable MR analyses were performed to assess the effects of obesity, diabetes mellitus, and smoking. A significant causal association between A Disintegrin and metalloproteinase domain-containing protein 23 (ADAM23) and head and neck cancer was noted. The sensitivity analysis indicated no significant bias. Multivariate analysis showed that the effect for ADAM23 remained significant after adjusting for the indirect effects of obesity, diabetes mellitus and smoking. In sum, this study showed a significant causal role of genetically dysregulated ADAM23 protein with head and neck cancer risk. The specific mechanisms underlying the role of ADAM23 in mediating head and neck cancer risk, and its role as a potential therapeutic target and biomarker, need further investigation.

Head and neck cancer (HNC) represents a significant global health challenge, with squamous cell carcinomas (SCCs) accounting for approximately 90% of all HNC cases. These malignancies, collectively referred to as head and neck squamous cell carcinoma (HNSCC), originate from the mucosal epithelium lining the larynx, pharynx, and oral cavity. The primary risk factors associated with HNSCC in economically disadvantaged nations have been chronic alcohol consumption and tobacco use. However, in more affluent countries, the landscape of HNSCC has shifted with the identification of human papillomavirus (HPV) infection, particularly HPV-16, as a major risk factor, especially among nonsmokers. Understanding the evolving risk factors and the distinct biological behaviors of HPV-positive and HPV-negative HNSCC is critical for developing targeted treatment strategies and improving patient outcomes in this complex and diverse group of cancers. Accurate diagnosis of HPV-positive HNSCC is essential for developing a comprehensive model that integrates the molecular characteristics, immune microenvironment, and clinical outcomes. The aim of this comprehensive review was to summarize the current knowledge and advances in the identification of DNA, RNA, and protein biomarkers in bodily fluids and tissues that have introduced new possibilities for minimally or non-invasive cancer diagnosis, monitoring, and assessment of therapeutic responses.

Long non-coding RNAs (lncRNAs) are key regulators of the 6-methyladenosine (m6A) epigenetic modification, playing a role in the initiation and progression of tumors. However, the regulatory mechanisms in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we investigated the molecular regulatory mechanisms of the lncRNA RASAL2-AS1 in the occurrence and development of HNSCC tumors.

A bioinformatics analysis was conducted to analyze the expression level of RASAL2-AS1 in HNSCC and normal tissues. RASAL2-AS1 mRNA and protein levels were detected using RT-PCR and Western blotting. Wound healing, transwell assays, flow cytometry, M6A dot blot, and RNA immunoprecipitation experiments were conducted to explore the regulatory role of the RASAL2-AS1 and downstream targets METTL14/LIS1 signaling pathway in HNSCC. Immunohistochemical examination was conducted to evaluate the expression of METTL14 and LIS1 in HNSCC and normal tissues. A tumor xenograft model of BALB/c nude mice was established to assess the impact of RASAL2-AS1 on cell proliferation and growth.

RASAL2-AS1 high expression in HNSCC and cells deteriorated with survival rates of HNSCC. RASAL2-AS1 overexpression in HNSCC accelerated cell migration, colony formation, cell proliferation, cell cycle in S stage, while RASAL2-AS1 knockdown in HNSC cells inhibited cell cycle in G1 stage. After silencing METTL14, the above effects induced by overexpression of the RASAL2-AS1 were reversed. RASAL2-AS1 overexpression prompted LIS1 expression, whereas RASAL2-AS1 silencing reduced LIS1 levels in HNSCC cells, which was confirmed by immunohistological staining. Results demonstrated elevated expression of METTL14 or LIS1 in tongue cancer tissues. Overexpression of RASAL2-AS1 promoted tumor weight and tumor volume, which was counteracted by pcDNA3.1 RASAL2-AS1 plus silencing METTL14 and METTL14 and LIS1 were significantly decreased.

Our study highlights the functional importance of the LncRNA RASAL2-AS1 in HNSCC and might assist in the development of a prognostic stratification and therapeutic approach. Which regulates HNSCC with the dependence of m6a manner.

Background: Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and in vitro testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. Materials and Methods: GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain (COL4A1) on the proliferation, migration, invasion, and apoptosis of TU686 cells. Results: Hub genes MMP10, MMP1, COL4A1, IFI27, and INHBA showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, IL-1B, IFI27, INHBA, and COL4A1 mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas COL4A1, MMP10, and INHBA expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of COL4A1 inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Conclusion: Ferroptosis-related hub genes, such as COL4A1, are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.

Precision healthcare has entered a new era because of the developments in personalized medicine, especially in the diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC). This paper explores the dynamic landscape of personalized medicine as applied to HNSCC, encompassing both current developments and future prospects.

The integration of personalized medicine strategies into HNSCC diagnosis is driven by the utilization of genetic data and biomarkers. Epigenetic biomarkers, which reflect modifications to DNA that can influence gene expression, have emerged as valuable indicators for early detection and risk assessment. Treatment approaches within the personalized medicine framework are equally promising. Immunotherapy, gene silencing, and editing techniques, including RNA interference and CRISPR/Cas9, offer innovative means to modulate gene expression and correct genetic aberrations driving HNSCC. The integration of stem cell research with personalized medicine presents opportunities for tailored regenerative approaches. The synergy between personalized medicine and technological advancements is exemplified by artificial intelligence (AI) and machine learning (ML) applications. These tools empower clinicians to analyze vast datasets, predict patient responses, and optimize treatment strategies with unprecedented accuracy.

The developments and prospects of personalized medicine in HNSCC diagnosis and treatment offer a transformative approach to managing this complex malignancy. By harnessing genetic insights, biomarkers, immunotherapy, gene editing, stem cell therapies, and advanced technologies like AI and ML, personalized medicine holds the key to enhancing patient outcomes and ushering in a new era of precision oncology.

Oral squamous cell carcinoma (OSCC) survival rates have remained stagnant due to a lack of targeted therapies and diagnostic tools. Patient risk is currently determined solely through clinicopathologic features, primarily tumor staging, which lacks the necessary precision to stratify patients by risk and accurately dictate adjuvant treatment. Similarly, conventional OSCC therapies have well-established toxicities and limited efficacy.

Recent studies show that patient risk can now be assessed using non-invasive techniques, at earlier time points, and with greater accuracy using molecular biomarker panels. Additionally, novel immunotherapies not only utilize the host's immune response to combat disease but also have the potential to form immunological memory to prevent future recurrence. Localized controlled-release formulas have further served to reduce toxicity and allow the de-escalation of other treatment modalities.

We review the latest advances in head and neck cancer diagnosis and treatment, including novel molecular biomarkers and immunotherapies.

Molecular diagnostics is an increasingly important clinical tool, especially in routine sampling. We evaluated two non-invasive methods (oral swabs and mouthwashes) for sampling nucleic acids from the oral/pharyngeal area. We created a workflow from sample collection (n = 59) to RT-qPCR based analysis. The samples were further characterized in terms of their cellular composition as well as the purity, degradation and microbial content of the derived DNA/RNA. We determined the optimal housekeeping genes applicable for these types of samples. The cellular composition indicated that mouthwashes contained more immune cells and bacteria. Even though the protocol was not specifically optimized to extract bacterial RNA it was possible to derive microbial RNA, from both sampling methods. Optimizing the protocol allowed us to generate stable quantities of DNA/RNA. DNA/RNA purity parameters were not significantly different between the two sampling methods. Even though integrity analysis demonstrated a high level of degradation of RNA, corresponding parameters confirmed their sequencing potential. RT-qPCR analysis determined TATA-Box Binding Protein as the most favorable housekeeping gene. In summary, we have developed a robust method suitable for multiple downstream diagnostic techniques. This protocol can be used as a foundation for further research endeavors focusing on developing molecular diagnostics for the oropharyngeal cavity.

Head and neck squamous cell carcinomas (HNSCCs) are the most devastating diseases in India and southeast Asia. It is a preventable and curable disease if detected early. Tobacco and alcohol consumption are the two major risk-factors but infection of high-risk HPVs are also associated with development of predominantly oral and oropharyngeal carcinomas. Interestingly, unlike cervical cancer, HPV-induced HNSCCs show good prognosis and better survival in contrast, majority of tobacco-associated HPV-ve HNSCCs are highly aggressive with poor clinical outcome. Biomarker analysis in circulatory body-fluids for early cancer diagnosis, prognosis and treatment monitoring are becoming important in clinical practice. Early diagnosis using non-invasive saliva for oral or other diseases plays an important role in successful treatment and better prognosis. Saliva mirrors the body's state of health as it comes into direct contact with oral lesions and needs no trained manpower to collect, making it a suitable bio-fluid of choice for screening. Saliva can be used to detect not only virus, bacteria and other biomarkers but variety of molecular and genetic markers for an early detection, treatment and monitoring cancer and other diseases. The performance of saliva-based diagnostics are reported to be highly (≥95 %) sensitive and specific indicating the test's ability to correctly identify true positive or negative cases. This review focuses on the potentials of saliva in the early detection of not only HPV or other pathogens but also identification of highly reliable gene mutations, oral-microbiomes, metabolites, salivary cytokines, non-coding RNAs and exosomal miRNAs. It also discusses the importance of saliva as a reliable, cost-effective and an easy alternative to invasive procedures.

Saliva is an important exocrine fluid that is easy to collect and is a complex mixture of proteins and other molecules from multiple sources from which considerable biological information can be mined. Pig saliva, as an easily available biological liquid rich in bioactive ingredients, is rich in nucleic acid analytes, such as eggs, enzymes, amino acids, sugars, etc. The expression levels of these components in different diseases have received extensive attention, and the analysis of specific proteins, metabolites, and biological compositions in pig saliva has become a new direction for disease diagnosis and treatment. The study of the changes in analytes in pig saliva can provide a new strategy for early diagnosis, prognosis assessment, and treatment of diseases. In this paper, the detection methods and research progress of porcine salivary analytes are reviewed, the application and research progress of porcine salivary analytes in diseases are discussed, and the future application prospect is presented.

Head and neck cancer ranks as the sixth most prevalent malignancy, constituting 5 % of all cancer cases. Its inconspicuous onset often leads to advanced stage diagnoses, prompting the need for early detection to enhance patient prognosis. Currently, research into early diagnostic markers relies predominantly on genomics, proteomics, transcriptomics, and other methods, which, unfortunately, necessitate tumor tissue homogenization, resulting in the loss of temporal and spatial information. Emerging as a recent addition to the omics toolkit, spatial metabolomics stands out. This method conducts in situ mass spectrometry analyses on fresh tissue specimens while effectively preserving their spatiotemporal information. The utilization of spatial metabolomics in life science research offers distinct advantages. This article comprehensively reviews the progress of spatial metabolomics in head and neck cancer research, encompassing insights into cancer cell metabolic reprogramming. Various mass spectrometry imaging techniques, such as secondary ion mass spectrometry, stroma-assisted laser desorption/ionization, and desorption electrospray ionization, enable in situ metabolite analysis for head and neck cancer. Finally, significant emphasis is placed on the application of presently available techniques for early diagnosis, margin assessment, and prognosis of head and neck cancer.

Tobacco use is implicated in the carcinogenesis of oral squamous cell carcinoma (OSCC), which is associated with poor survival if not diagnosed early. Identification of novel noninvasive, highly sensitive, and cost-effective diagnostic and risk assessment methods for OSCC would improve early detection. Here, we report a pilot study assessing salivary and serum miRNAs associated with OSCC and stratified by smoking status. Saliva and paired serum samples were collected from 23 patients with OSCC and 21 healthy volunteers, with an equal number of smokers and nonsmokers in each group. Twenty head and neck cancer-related miRNAs were quantified by qPCR (dual-labeled LNA probes) and analyzed by Welch t test (95% confidence interval). Four saliva miRNAs, miR-21, miR-136, miR-3928, and miR-29B, showed statistically significant overexpression in OSCC versus healthy controls (P < 0.05). miR-21 was statistically significantly overexpressed in OSCC smokers versus nonsmokers (P = 0.006). Salivary miR-21, miR-136, and miR-3928, and serum miR-21 and miR-136, showed statistically significant differential expression in early-stage tumors versus controls (P < 0.05), particularly miR-21 in smokers (P < 0.005). This pilot study provides a novel panel of saliva and serum miRNAs associated with oral cancer. Further validation as a potential useful index of oral cancer, particularly miR-21 in smokers and early-stage OSCC is warranted.

Saliva and serum miR-21, miR-136, miR-3928, and miR-29B, are potentially associated with oral cancer even at an early stage, especially miR-21 in individuals with a smoking history, a further validation in a larger cohort of subjects with premalignant and early malignant lesions need to confirm.

Survival rates for oral squamous cell carcinoma (OSCC) have remained poor for decades, a fact largely attributable to late-stage diagnoses and high recurrence rates. We report analysis of serum miRNA expression in samples from patients with high-risk oral lesions (HRL, including OSCC/carcinoma in situ lesions) and healthy non-cancer controls, with the aim of non-invasively detecting primary or recurrent disease before it is clinically evident.

Discovery, test, and validation sets were defined from a total of 468 serum samples (305 HRL and 163 control samples). Samples were analysed using multiple qRT-PCR platforms.

A two-miRNA classifier comprised of miR-125b-5p and miR-342-3p was defined following discovery and test analyses. Analysis in an independent validation cohort reported sensitivity and specificity of ~74% for this classifier. Significantly, when this classifier was applied to serial serum samples taken from patients both before treatment and during post-treatment surveillance, it identified recurrence an average of 15 months prior to clinical presentation.

These results indicate this serum miRNA classifier is effective as a simple, non-invasive monitoring tool for earlier detection of recurrent disease when lesions are typically smaller and amenable to a wider array of treatment options to improve survival.

This study aimed to investigate the relevance of cerebral endothelial cell adhesion molecule (CERCAM) expression to head and neck squamous cell carcinoma (HNSCC) prognosis and immune infiltration by macrophage M2 polarization.

Timer, UALCAN and HPA databases was used to analyze the differences in mRNA and protein levels of CERCAM expression in HNSCC. The Timer database was also applied to analyze the correlation between CERCAM in HNSCC and immune infiltration. TCGA-HNSCC database was applied to analyze the correlation between CERCAM expression levels and clinicopathological features, and its diagnostic and prognostic value in HNSCC was also assessed. The cBioPortal and MethSurv databases were then applied to analyze the genetic variation and methylation status of CERCAM. In vitro cellular assays were performed to provide evidence that CERCAM promotes malignant biological behavior of tumors and promotes macrophage M2 polarization in tumors. Finally, underlying pathophysiological mechanisms of CERCAM involvement in the development of HNSCC were predicted using a bioinformatics approach.

CERCAM is significantly overexpressed in HNSCC and correlates with poor prognostic levels and has good performance in predicting survival status in HNSCC patients. Cox regression analysis indicates that CERCAM expression levels are independent risk factors for predicting OS, DSS, and PFI. CERCAM promotes tumor malignant biological behavior and promotes macrophage M2 polarization immune infiltration in HNSCC. In addition, CERCAM promotes tumor cell adhesion in head and neck squamous carcinoma and promotes tumor progression through several oncogenic signaling pathways.

CERCAM may serve as a new diagnostic and prognostic biomarker in HNSCC and is a promising therapeutic target for HNSCC.

Oral cancer is the sixth-most common cancer globally. The survival rate of oral cancer is 5 years, depending on the stage it is diagnosed. To diagnose in the early stage, specialised tumour markers may assist and also help in improving the survival rate of oral cancer. ErbB2 is a transmembrane cell surface receptor required in signal transduction and an essential part of signalling pathways that take part in controlling the basic cellular processes like cell cycle, migration, metabolism and survival, besides cellular proliferation and differentiation. It is over-expressed in oral squamous cell carcinoma (OSCC) and is directly proportional to the poor prognosis, as it is expressed at a very low concentration in a healthy individual. Due to this, ErbB2 could be used as a diagnostic marker in OSCC. Nowadays, the search for tumour expression in the saliva with the use of salivary biomarkers could aid in the diagnosis of the OSSC.

To assess the expression of ErbB2 in the saliva of patients with oral squamous cell carcinoma by correlating the ErbB2 level in the disease group with the healthy group. To determine the diagnostic significance of ErbB2 in OSCC.

The study comprises 20 salivary samples from OSCC patients and 20 salivary samples from healthy individuals. The salivary level of ErbB2 was estimated using Enzyme Linked Immunosorbent Assay. To analyse the data, SPSS (IBM SPSS Statistics for Windows, Version 26.0, Armonk, NY: IBM Corp. Released 2019) is used. The significance level is fixed at 5% (α = 0.05). P value <0.05 is considered to be statistically significant. To compare the mean values of mean and concentration, an unpaired/independent sample t-test was used.

The mean age of OSCC and control were found to be 57 ± 8.13 and 26.6 ± 1.51, respectively. The mean age was compared between OSCC and control by the Chi-square test, and the P value was <0.01, which was found to be statistically significant. The salivary levels of ErbB2 in the OSCC and control groups were measured by an unpaired sample t-test. The mean salivary ErbB2 level in the OSCC group is 3.20 ng/ml ± 0.57, and in the control group, it is 2.43 ng/ml ± 0.13. When a pairwise comparison of ErbB2 concentration was performed between OSCC and control, it showed a statistically significant difference with a P value of 0.007, which is P < 0.05.

The present study has demonstrated an increased salivary expression of ErbB2 in OSCC patients when compared to healthy individuals. This suggests that ErbB2 could aid in the diagnosis of OSCC and could be used as a diagnostic marker in the early detection of oral cancer, a finding that has to be further established with a larger sample size.

Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we hereby propose a retrospective in silico study to shed light on gene-miRNA interactions driving the development of HNSCC. Moreover, to identify topological biomarkers as a source for designing new drugs. To achieve this, gene and miRNA profiles from patients and controls are holistically reevaluated using protein-protein interaction (PPI) and bipartite miRNA-target networks. Cytoskeletal remodeling, extracellular matrix (ECM), immune system, proteolysis, and energy metabolism have emerged as major functional modules involved in the pathogenesis of HNSCC. Of note, the landscape of our findings depicts a concerted molecular action in activating genes promoting cell cycle and proliferation, and inactivating those suppressive. In this scenario, genes, including VEGFA, EMP1, PPL, KRAS, MET, TP53, MMPs and HOXs, and miRNAs, including mir-6728 and mir-99a, emerge as key players in the molecular interactions driving HNSCC tumorigenesis. Despite the heterogeneity characterizing these HNSCC subtypes, and the limitations of a study pointing to relationships that could be context dependent, the overlap with previously published studies is encouraging. Hence, it supports further investigation for key molecules, both those already and not correlated to HNSCC.

The World Health Organization (WHO) has stated that countless cancer patients could be saved if early detection and treatment were available. However, current clinical evaluation of tumors still relies primarily on imaging examinations and tissue biopsies. These methods not only require sophisticated equipment, but also have high false positive rates or invasive problems. Here, we describe a digital polymerase chain reaction (dPCR) chip for the detection of biomarkers in salivary extracellular vesicles (SEVs), which can be used to identify markers for the early diagnosis of tumors. Based on microfluidic technology fine microstructure and microfluidics operations, this dPCR chip can accurate quantitative SEVs in a variety of tumor markers, and shows extremely strong sensitivity (10 copies). In the detection of clinical samples, the chip can effectively distinguish lung cancer cases from normal controls (P < 0.001; two-tailed t-test), and in the detection of extremely low concentration samples, it shows considerably higher precise quantitative ability than quantitative real-time polymerase chain reaction (qPCR). Overall, this study may shed new light on non-invasive early screening of tumor markers by detecting extracellular vesicle-associated markers in saliva.

The most common tumor affecting the head and neck is head and neck squamous cell carcinoma (HNSCC). The characteristics of HNSCC include a rapid onset, a lack of early diagnosis, drug resistance, relapse and systemic adverse effects, leading to inadequate prevention, diagnosis and treatment. Notably, previous research suggests that there is an association between S100 proteins and HNSCC. S100A8, S100A9 and S100A14 interfere with tumor cell proliferation by blocking the cell cycle. The present review discusses this association. S100A4 enhances cancer stem cell properties, and interacts with actin and tropomyosin to promote tumor cell migration. S100A1, S100A8, S100A9, S100A10, S100A14 and S100P are involved in the initiation and progression of HNSCC via Hippo, nuclear factor κB, phosphatidylinositol kinase/protein kinase B/mammalian target of rapamycin and other signaling pathways. In addition, certain long non-coding RNAs and microRNAs are involved in regulating the expression of S100 proteins in HNSCC. Reducing the expression of certain members of the S100 protein family may enhance the chemosensitivity of HNSCC. Collectively, it is suggested that S100 proteins may function as markers and targets for the prevention, diagnosis and treatment of HNSCC.

As the second most common malignant tumor in the world, lung cancer is a great threat to human health. In the past several decades, the role and mechanism of ncRNAs in lung cancer as a class of regulatory RNAs have been studied intensively. In particular, ncRNAs in body fluids have attracted increasing attention as biomarkers for lung cancer diagnosis and prognosis and for the evaluation of lung cancer treatment due to their low invasiveness and accessibility. As emerging tumor biomarkers in lung cancer, circulating ncRNAs are easy to obtain, independent of tissue specimens, and can well reflect the occurrence and progression of tumors due to their correlation with some biological processes in tumors. Circulating ncRNAs have a very high potential to serve as biomarkers and hold promise for the development of ncRNA-based therapeutics. In the current study, there has been extensive evidence that circulating ncRNA has clinical significance and value as a biomarker. In this review, we summarize how ncRNAs are generated and enter the circulation, remaining stable for subsequent detection. The feasibility of circulating ncRNAs as biomarkers in the diagnosis and prognosis of non-small cell lung cancer is also summarized. In the current systematic treatment of non-small cell lung cancer, circulating ncRNAs can also predict drug resistance, adverse reactions, and other events in targeted therapy, chemotherapy, immunotherapy, and radiotherapy and have promising potential to guide the systematic treatment of non-small cell lung cancer.

Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa, which has potential for malignant transformation. MicroRNAs play an important role in immunopathogenesis of OLP, and may be used for prediction of its malignant transformation. This study aimed to assess the salivary level of microRNA-146a and microRNA-155 biomarkers in patients with OLP and oral squamous cell carcinoma (OSCC).

In this case-control study, unstimulated saliva samples were collected from 60 patients, including 15 patients with dysplastic OLP, 15 OLP patients without dysplasia, 15 patients with OSCC, and 15 healthy controls according to the Navazesh technique. After RNA extraction, the expression of microRNA-146a and microRNA-155 was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). The data were analyzed by the Kruskal-Wallis and Dunn-Bonferroni tests.

The difference in expression of microRNA-146a and microRNA-155 among the four groups was significant (P < 0.05). Pairwise comparisons of the groups showed significantly higher expression of microRNA-146a in OLP (P = 0.004) and dysplastic OLP (P = 0.046) patients compared with the control group. Up-regulation of this biomarker in OSCC patients was not significant compared with the control group (P = 0.076). Up-regulation of micro-RNA-155 was only significant in OLP group, compared with the control group (P = 0.009). No other significant differences were found (P > 0.05).

Considering the altered expression of MicroRNA-146a and microRNA-155 in dysplastic OLP and OSCC, their altered expression may serve as an alarming sign of malignancy. However, further investigations are still required.

Laryngeal squamous cell carcinoma (LSCC) is one of the most aggressive cancers, and its early diagnosis is urgent. Exosomes are believed to have diagnostic significance in cancer. However, the role of serum exosomal microRNAs, miR-223, miR-146, and miR-21, and phosphatase and tensin homologue (PTEN) and hemoglobin subunit delta (HBD) mRNAs in LSCC is unclear. Exosomes were isolated from the blood serum of 10 LSCC patients and 10 healthy controls to perform scanning electron microscopy and liquid chromatography quadrupole time-of-flight mass spectrometry analyses to characterize them and to undergo reverse transcription polymerase chain reaction to identify miR-223, miR-146, miR-21, and PTEN and HBD mRNA expression phenotypes. Biochemical parameters, including serum C-reactive protein (CRP) and vitamin B12, were also obtained. Serum exosomes of 10-140 nm were isolated from LSCC and controls. Serum exosomal miR-223, miR-146, and PTEN were found to be significantly decreased (p < 0.05), in contrast to serum exosomal miRNA-21 (p < 0.01), and serum vitamin B12 and CRP (p < 0.05) were found to be significantly increased, in LSCC vs controls. Our novel data show that the combination of reduced serum exosomal miR-223, miR-146, and miR-21 profiles and biochemical alterations in CRP and vitamin B12 levels may be useful indicators of LSCC that could be validated by large studies. Our findings also suggest a possible negative regulatory effect of miR-21 on PTEN in LSCC, encouraging a more extensive investigation of its role.

The proportion of oral and oropharyngeal squamous cell carcinoma (OOSCC) that can be attributed to human papillomavirus (HPV) infection is growing nowadays. A potential factor indicating the occurrence of HPV-positive OSCC is a change in the degree of methylation of gene promoters that play a key role in the immune response. In this study, we investigated the difference in the methylation of EDARADD, GBP4, HAVCR2, HLA DPB1, IL12RB1, MARCO, and SIGLEC12 gene promoters in samples of healthy oral mucosa versus samples of oral and oropharyngeal cancer. The presence of HPV infection in samples was examined earlier. To determine the difference in methylation of those gene promotors, isolated and bisulfite-modified DNA was analysed by the methylation-specific PCR method. The investigated gene promoters were found to be more hypomethylated in the oral and oropharyngeal cancer samples in comparison to normal tissue. The proportion of unmethylated gene promoters was similar in HPV-positive and HPV-negative cancers, although the data should be confirmed on a larger set of samples. To conclude, in samples of healthy oral mucosa, the investigated gene promoters were found to be methylated in a high percentage (73.3% to 100%), while in oral and oropharyngeal cancer samples, they were methylated in a low percentage (11.1% to 37%), regardless of HPV infection.

Head and neck radiotherapy induces important toxicity, and its efficacy and tolerance vary widely across patients. Advancements in radiotherapy delivery techniques, along with the increased quality and frequency of image guidance, offer a unique opportunity to individualize radiotherapy based on imaging biomarkers, with the aim of improving radiation efficacy while reducing its toxicity. Various artificial intelligence models integrating clinical data and radiomics have shown encouraging results for toxicity and cancer control outcomes prediction in head and neck cancer radiotherapy. Clinical implementation of these models could lead to individualized risk-based therapeutic decision making, but the reliability of the current studies is limited. Understanding, validating and expanding these models to larger multi-institutional data sets and testing them in the context of clinical trials is needed to ensure safe clinical implementation. This review summarizes the current state of the art of machine learning models for prediction of head and neck cancer radiotherapy outcomes.

Head and neck squamous cell carcinoma (HNSCC), is one of the malignant tumors with high recurrence and metastasis. The family with sequence similarity (FAM) of non-coding RNAs promoted tumorigenesis and metastasis. But so far, long non-coding RNA (lncRNA) FAM239A's function in HNSCC regulation remains unclear. This study aimed to explore the lncRNA FAM239A function and regulation mechanism in HNSCC cell proliferation and migration.

The expression level of lncRNA FAM239A and tyrosine phosphatase Src homology 2 domain-containing phosphatase 2 (SHP2) in HNSCC tumor tissue was tested by quantitative polymerase chain reaction. The cell proliferation and migration were tested by cell counting kit 8, kinetic live cell assay, and wound healing assay. The differential expression of SHP2 and immune infiltration in HNSCC were analyzed in the tumor immune estimation response and human protein atlas databases. And the survival analysis of SHP2 in HNSCC was analyzed in the gene expression profiling interactive analysis 2 databases. The SHP2 expression was tested by western blotting when lncRNA FAM239A overexpression and knockdown.

LncRNA FAM239A and SHP2 were ectopically expressed in HNSCC tumor tissue. Cell proliferation and wound healing assays showed that lncRNA FAM239A promoted tumor cell proliferation and migration. SHP2 was overexpressed in HNSCC tumor tissue by database analyses, and the higher SHP2 expression caused poorer overall survival and disease-free survival in HNSCC patients. SHP2 expression was positively regulated by lncRNA FAM239A.

LncRNA FAM239A promoted HNSCC cell proliferation and migration through upregulating SHP2 expression, which potentially provided new regulators for HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a term collectively used to describe all cancers that develop in the oral and nasal cavities, the paranasal sinuses, the salivary glands, the pharynx, and the larynx. The majority (75%) of all newly diagnosed cases are observed in patients with locally advanced and aggressive disease, associated with significant relapse rates (30%) and poor prognostic outcomes, despite advances in multimodal treatment. Consequently, there is an unmet need for the identification and application of tools that would enable diagnosis at the earliest possible stage, accurately predict prognostic outcomes, contribute to the timely detection of relapses, and aid in the decision for therapy selection. Recent evidence suggests that DNA methylation can alter the expression of genes in a way that it favors tumorigenesis and tumor progression in HNSCC, and therefore represents a potential source for biomarker identification. This study summarizes the current knowledge on how abnormally methylated DNA profiles in HNSCC patients may contribute to the pathogenesis of HNSCC and designate the methylation patterns that have the potential to constitute clinically valuable biomarkers for achieving significant advances in the management of the disease and for improving survival outcomes in these patients.

Genomic instability is considered a fundamental factor involved in any neoplastic disease. Consequently, the genetically unstable cells contribute to intratumoral genetic heterogeneity and phenotypic diversity of cancer. These genetic alterations can be detected by several diagnostic techniques of molecular biology and the detection of alteration in genomic integrity may serve as reliable genetic molecular markers for the early detection of cancer or cancer-related abnormal changes in the body cells. These genetic molecular markers can detect cancer earlier than any other method of cancer diagnosis, once a tumor is diagnosed, then replacement or therapeutic manipulation of these cancer-related abnormal genetic changes can be possible, which leads toward effective and target-specific cancer treatment and in many cases, personalized treatment of cancer could be performed without the adverse effects of chemotherapy and radiotherapy. In this review, we describe how these genetic molecular markers can be detected and the possible ways for the application of this gene diagnosis for gene therapy that can attack cancerous cells, directly or indirectly, which lead to overall improved management and quality of life for a cancer patient.

Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including the long intergenic non-coding RNA, regulator of reprogramming (linc-ROR), which mostly exerts its role as an onco-lncRNA acting as a competing endogenous RNA that sequesters micro RNAs. Although the properties of linc-ROR in relation to some cancers have been reviewed in the past, active research appends evidence constantly to a better comprehension of the role of linc-ROR in different stages of cancer. Moreover, the molecular details and some recent papers have been omitted or partially reported, thus the importance of this review aimed to contribute to the up-to-date understanding of linc-ROR and its implication in cancer tumorigenesis, progression, metastasis, and chemoresistance. As the involvement of linc-ROR in cancer is elucidated, an improvement in diagnostic and prognostic tools could promote and advance in targeted and specific therapies in precision oncology.

Low milk supply (LMS) is associated with early breastfeeding cessation; however, the biological underpinnings in the mammary gland are not understood. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally downregulate gene expression, and we hypothesized the profile of miRNAs secreted into milk reflects lactation performance. Longitudinal changes in milk miRNAs were measured using RNAseq in women with LMS (n = 47) and adequate milk supply (AMS; n = 123). Relationships between milk miRNAs, milk supply, breastfeeding outcomes, and infant weight gain were assessed, and interactions between milk miRNAs, maternal diet, smoking status, and BMI were determined. Women with LMS had lower milk volume (p = 0.003), were more likely to have ceased breast feeding by 24 wks (p = 0.0003) and had infants with a lower mean weight-for-length z-score (p = 0.013). Milk production was significantly associated with milk levels of miR-16-5p (R = -0.14, adj p = 0.044), miR-22-3p (R = 0.13, adj p = 0.044), and let-7g-5p (R = 0.12, adj p = 0.046). Early milk levels of let-7g-5p were significantly higher in mothers with LMS (adj p = 0.0025), displayed an interaction between lactation stage and milk supply (p < 0.001), and were negatively related to fruit intake (p = 0.015). Putative targets of let-7g-5p include genes important to hormone signaling, RNA regulation, ion transport, and the extracellular matrix, and down-regulation of two targets (PRLR and IGF2BP1/IMP1) was confirmed in mammary cells overexpressing let-7g-5p in vitro. Our data provide evidence that milk-derived miRNAs reflect lactation performance in women and warrant further investigation to assess their utility for predicting LMS risk and early breastfeeding cessation.

Cell-to-cell interactions in the intricate microenvironment of tissue have a significant impact on the progression of cancer at every stage. Both cancer cells and stromal cells are responsible for the secretion of soluble chemical compounds as well as membrane-encased components, which both influence and govern the cell-to-cell interactions within the micro-environment of tumor cells. These membrane structures are identified as extracellular vesicles (EVs), which include exosomes and microvesicles. These nanosized vesicles are made up of bilayered proteolipids and have dimensions ranging from 50 to 1000 nm. It has been speculated that extracellular vesicles that originate from cancer cells perform a variety of functions in the development and progression of cancer which may involve the transport of regulatory materials, such as oncogenic proteins between nearby cells and to distant biological locations. In addition, their level in the serum of cancer patients is noticeably higher than those of healthy controls. The release of extracellular vesicles into the extracellular space is a continual process in both healthy and diseased cells. These extracellular vesicles hold molecular signatures that are defining features of health as well as disease. And hence, the EVs present in biological fluids provide unparalleled and noninvasive access to the necessary molecular details about the health status of the cells. Recent discoveries about these complex extracellular organelles have accelerated the discovery of cancer-specific biological markers as well as the development of unique diagnostic tools based on extracellular vesicles. In this mini-review, we aim to highlight the hopes and hypes associated with the applications of extracellular vesicles as biomarkers for cancer diagnosis.

Saliva testing is a vital method for clinical applications, for its noninvasive features, richness in substances, and the huge amount. Due to its direct anatomical connection with oral, digestive, and endocrine systems, clinical usage of saliva testing for these diseases is promising. Furthermore, for other diseases that seeming to have no correlations with saliva, such as neurodegenerative diseases and psychological diseases, researchers also reckon saliva informative. Tremendous papers are being produced in this field. Updated summaries of recent literature give newcomers a shortcut to have a grasp of this topic. Here, we focused on recent research about saliva biomarkers that are derived from humans, not from other organisms. The review mostly addresses the proceedings from 2016 to 2022, to shed light on the promising usage of saliva testing in clinical diagnostics. We recap the recent advances following the category of different types of biomarkers, such as intracellular DNA, RNA, proteins and intercellular exosomes, cell-free DNA, to give a comprehensive impression of saliva biomarker testing.

Analysis of methylomes may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to identify methylation-related differentially expressed genes (mrDEGs), and to assess their efficacy in predicting patients' survival, tumor immune microenvironment alterations and immune checkpoints in patients with HNSCC.

The methylome and transcriptome data of 528 HNSCC and 50 normal samples from TCGA database were used as training cohort. We identified mrDEGs and constituted a risk score model using Kaplan-Meier analysis and multivariate Cox regression. The prognostic efficacy of the risk score was validated in GSE65858 and GSE41613. We determined the enrichment of previously defined biological processes of mrDEGs. We separated the HNSCC patients into low-risk and high-risk groups and compared their immune cell infiltration and immune checkpoints' expressions.

The risk score model was constituted by nine prognostic mrDEGs, including LIMD2, SYCP2, EPHX3, UCLH1, STC2, PRAME, SLC7A4, PLOD2, and ACADL. The risk score was a significant prognostic factor both in training (P < 0.001) and validation dataset (GSE65858: P = 0.008; GSE41613 = 0.015). The prognostic mrDEGs were enriched in multiple immune-associated pathways. Effector immune cells were increased in low-risk patients, including CD8+ T cells, activated CD4+ T cells, and plasma cells, whereas tumor associated M2 macrophages were recruited in the high-risk group. Expressions of immune checkpoints were generally higher in low-risk patients, including CTLA-4, PD-1 and LAG3.

The mrDEGs can stratify HNSCC patients' prognosis, which correlates with alterations in tumor immune infiltrations and immune checkpoints.

Although exosomal microRNAs (exo-miRNAs) regulate angiogenesis, they are not sufficient for the development of anti-vascular drugs for tongue squamous cell carcinoma (TSCC). miR-205-5p is an exo-miRNA that is highly expressed in the saliva of patients with oral SCC.

We aimed to clarify the role and molecular mechanism of exosomal miR-205-5p in regulating TSCC angiogenesis.

Effect of exosomes derived from TSCC cells on human umbilical vein endothelial cell (HUVEC) function was determined using the CCK-8, Transwell, Transwell-Matrigel, and Matrigel-based tube formation assays. Protein levels were detected by western blot. The binding between miR-205-5p and the 3'UTR of AMOT was verified using a luciferase reporter assay.

Exosomal miR-205-5p (exo-miR-205-5p) promoted the proliferation, migration, and invasion of HUVECs, increased the number of tubes formed by HUVECs, and increased the vascular endothelial growth factor receptor 2 levels in HUVECs. Exo-miR-205-5p downregulated the AMOT level in HUVECs. Results of the luciferase reporter assay showed that miR-205-5p could bind to the 3'UTR of AMOT. AMOT overexpression blocked the effect of exo-miR-205-5p on HUVEC functions.

Exo-miR-205-5p derived from TSCC regulates the angiogenic activity of HUVECs by targeting AMOT and might be a new molecular target for the development of anti-vascular drugs for TSCC.

The analysis of the combined mRNA and miRNA content of a biological sample can be of interest for answering several research questions, like biomarkers discovery, or mRNA-miRNA interactions. However, the process is costly and time-consuming, separate libraries need to be prepared and sequenced on different flowcells. Combo-Seq is a library prep kit that allows us to prepare combined mRNA-miRNA libraries starting from very low total RNA. To date, no dedicated bioinformatics method exists for the processing of Combo-Seq data. In this paper, we describe CODA (Combo-seq Data Analysis), a workflow specifically developed for the processing of Combo-Seq data that employs existing free-to-use tools. We compare CODA with exceRpt, the pipeline suggested by the kit manufacturer for this purpose. We also evaluate how Combo-Seq libraries analysed with CODA perform compared with conventional poly(A) and small RNA libraries prepared from the same samples. We show that using CODA more successfully trimmed reads are recovered compared with exceRpt, and the difference is more dramatic with short sequencing reads. We demonstrate how Combo-Seq identifies as many genes and fewer miRNAs compared to the standard libraries, and how miRNA validation favours conventional small RNA libraries over Combo-Seq. The CODA code is available at https://github.com/marta-nazzari/CODA.

Head and neck cancer (HNC), also known as the cancer that can affect the structures between the dura mater and the pleura, is the 6th most common type of cancer. This heterogeneous group of malignancies is usually treated with a combination of surgery and radio- and chemotherapy, depending on if the disease is localized or at an advanced stage. However, most HNC patients are diagnosed at an advanced stage, resulting in the death of half of these patients. Thus, the prognosis of advanced or recurrent/metastatic HNC, especially HNC squamous cell carcinoma (HNSCC), is notably poorer than the prognosis of patients diagnosed with localized HNC. This review explores the epidemiology and etiologic factors of HNC, the histopathology of this heterogeneous cancer, and the diagnosis methods and treatment approaches currently available. Moreover, special interest is given to the novel therapies used to treat HNC subtypes with worse prognosis, exploring immunotherapies and targeted/multi-targeted drugs undergoing clinical trials, as well as light-based therapies (i.e., photodynamic and photothermal therapies).

Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium.

A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test.

We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls.

We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status.

The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.

Biomarkers are of major interest to optimize diagnosis, prognosis and to guide treatment in head and neck cancer patients. Especially blood-based biomarkers appear promising as they can be easily collected and repeatedly analyzed during the course of radiochemotherapy.

At first, for a broad overview, multiple immune markers were evaluated in six plasma samples of three head and neck squamous cell carcinoma (HNSCC) patients at the beginning and the end of radio-chemotherapy. In this pre-selection, the soluble Intercellular Adhesion Molecule 1 (sICAM-1) appeared most promising. Thus, this marker was measured in multiple samples (n = 86) during treatment and follow-up in a cohort of eleven patients and correlated with tumor features and clinical data.

We found a strong correlation between the initial levels of sICAM-1 in the plasma and the gross tumor volumes of the primary tumor and the involved lymph nodes. However, during the course of treatment no systematic dynamics could be identified. Toxicity or infections did not seem to influence sICAM-1 concentrations.

sICAM-1 appears to reflect the pre-treatment total tumor burden (primary tumor and involved lymph nodes) in head and neck tumor patients. However, it does not seem to be a dynamic marker reflecting response during radiochemotherapy. Thus, if our findings are confirmed in future, sICAM-1 could be used as a staging marker: if high sICAM-1 levels but low tumor burden are found it might be reasonable to intensify staging investigations to rule out further, yet undetected, tumor sites.

Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic meta-analysis to evaluate the diagnostic value of noncoding salivary RNAs in pancreatic cancer diagnosis.

Our investigation involved pertinent studies published in PubMed, Scopus, Web of Science, LIVIVO, Ovid and also the Google Scholar search engine. Specificity and sensitivity were calculated, as were positive and negative likelihood ratios (PLR and NLR), and the diagnostic odds ratio (DOR). The summary receiver-operating characteristics and area under the curve were plotted and assessed.

This meta-analysis and systematic review involved and examined five studies that contained 145 study units with a total of 2731 subjects (1465 pancreatic cancer patients versus 1266 noncancer controls). The pooled specificity, sensitivity, NLR, PLR and DOR were 0.783 (95% CI: 0.759-0.805), 0.829 (95% CI: 0.809-0.848), 0.309 (95% CI: 0.279-0.343), 3.386 (95% CI: 2.956-3.879) and 18.403 (95% CI: 14.753-22.954), respectively, with the area under the curve (AUC) equal to 0.882. Subgroup analyses were conducted based on the saliva type (unstimulated and stimulated), mean age of patients, sample size, type of control, serum carbohydrate antigen 19-9 (CA19-9) level and type of salivary noncoding RNA (microRNA (miRNA) and long noncoding RNA (lncRNA)).

The results of our systematic review and meta-analysis suggest that noncoding RNA biomarkers in the stimulated saliva could be a promising approach for accurate pancreatic cancer diagnosis in the early stages.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with an increasing trend of its incidence. Alcohol consumption, smoking, and viral infections, such as the mucosal high-risk (HR) human papillomaviruses (HPVs) are major risk factors for HNSCC development. In particular, HR HPVs are mainly associated with a subset of oropharyngeal squamous cell carcinoma (OPSCC), while other head and neck sites are marginally affected by HPV infection. HPV16 is the most frequently HR HPV type associated with HNSCC. In contrast to the cervix, no screening programs or identifiable pre-malignant lesions have been characterized for HPV-related HNSCC. Therefore, identification of general diagnostic algorithms and HPV biomarkers that could facilitate the early diagnosis, disease evolution and recurrence for HPV-driven HNSCCs are urgently needed. We herein review the role of HPV in HNSCC with a focus on epidemiology, biology, applied diagnostic algorithms and available biomarkers in body fluids as early diagnostic tools in HPV-driven HNSCCs.

Head and neck squamous cell carcinoma (HNSCC), the most common head and neck malignant tumor, with only monotherapy, is characterized by poor prognosis, and low 5-year survival rate. Due to the lack of therapeutic targets, the targeted drugs for HNSCC are rare. Therefore, exploring the regulation mechanism of HNSCC and identifying effective therapeutic targets will be beneficial to its treatment of. Circular RNA (CircRNA) is a class of RNA molecules with a circular structure, which is widely expressed in human body. CircRNAs regulate gene expression by exerting the function as a miRNA sponge, thereby mediating the occurrence and development of HNSCC cell proliferation, apoptosis, migration, invasion, and other processes. In addition, circRNAs are also involved in the regulation of tumor sensitivity to chemical drugs and other biological functions. In this review, we systematically listed the functions of circRNAs and explored the regulatory mechanisms of circRNAs in HNSCC from the aspects of tumor growth, cell death, angiogenesis, tumor invasion and metastasis, tumor stem cell regulation, tumor drug resistance, immune escape, and tumor microenvironment. It will assist us in discovering new diagnostic markers and therapeutic targets, while encourage new ideas for the diagnosis and treatment of HNSCC.