Treatment Of Head And Neck Squamous Cell Carcinoma Research Articles

Immune microenvironment of human papillomavirus-positive head and neck squamous cell carcinoma.

Research progress of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) based on immune microenvironment. This article preliminarily discusses the composition of immune microenvironment components and immune therapy and elaborates and analyzes the involvement and impact of T cells, B cells, natural killer (NK) cells, tumor-associated fibroblasts, and bone marrow-derived suppressor cells in HPV-positive HNSCC on tumor progression and prognosis. Furthermore, the application of immune-related therapies in HPV-positive HNSCC is explored. It is found that immune microenvironment research plays an important role in the pathogenesis and treatment of HPV-positive HNSCC. Immune microenvironment research as an important means to explore tumors has played an important role in the study of HPV-positive HNSCC. We describe the biological significance of important components of HNSCC immune microenvironment by analyzing the effects of HNSCC immune microenvironment components and immunotherapy on HPV-positive HNSCC. May to provide new strategies for experimental research and clinical prevention and treatment of this disease.

Comprehensive Investigation of m6A Regulators for Prognosis in Head and Neck Squamous Cell Carcinoma.

The early detection of head and neck squamous cell carcinoma (HNSCC) has an important impact on the clinical prognosis. N6-methyladenosine (m6A) is involved in the post-transcriptional regulation of tumorigenesis and development. In this study, the prognosis and biological functions of m6A regulator targets in HNSCC were explored. RNA-Seq expression data and clinical information from TCGA-HNSCC and GSE23036 datasets were collected. The mRNA levels of IGF2BP2 and IGF2BP3 in tumor tissues were significantly up-regulated. Differential expression and functional enrichment analysis of potential targets for IGF2BP2 and IGF2BP3 obtained from the m6A2Target database showed that they were significantly enriched in cell cycle-related pathways. The Cox regression analysis was performed to establish a three-mRNA signature including PLAU, LPIN1 and AURKA. The prognostic effect was verified in the external dataset GSE41613. Further studies revealed that the three-mRNA signature was significantly associated with survival in the clinical subgroup. The ROC curve, Harrell consistency index and decision curve comparison used to compare the predictive effect of the three-mRNA signature and the other signatures in previous studies showed that the three-mRNA signature had better predictive effect on the prognosis of HNSCC patients. The three-mRNA signature expression were verified in HNSCC cell lines with qRT-PCR and Western blot. Sequence analysis showed that m6A-modification sites existed on PLAU, LPIN1 and AURKA genes. In conclusion, the three-mRNA signature has been proved to be useful on evaluating the prognosis and contributing to the personalized treatment of HNSCC, and IGB2BP2/3 were related to the cell cycle in HNSCC.

Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma.

We showed that microtubule-associated tumor suppressor gene (MTUS1/ATIP) downregulation correlated with poor survival in head and neck squamous cell carcinoma (HNSCC) patients and that MTUS1/ATIP1 was the most abundant isoform in HNSCC tissue. However, the location and function of MTUS1/ATIP1 have remain unclear. In this study, we confirmed that MTUS1/ATIP1 inhibited proliferation, growth and metastasis in HNSCC in cell- and patient-derived xenograft models in vitro and in vivo. MTUS1/ATIP1 localized in the outer mitochondrial membrane, influence the morphology, movement and metabolism of mitochondria and stimulated oxidative stress in HNSCC cells by directly interacting with MFN2. MTUS1/ATIP1 activated ROS, recruiting Bax to mitochondria, facilitating cytochrome c release to the cytosol to activate caspase-3, and inducing GSDME-dependent pyroptotic death in HNSCC cells. Our findings showed that MTUS1/ATIP1 localized in the outer mitochondrial membrane in HNSCC cells and mediated anticancer effects through ROS-induced pyroptosis, which may provide a novel therapeutic strategy for HNSCC treatment.

Factors associated with radiation treatment delay in head and neck squamous cell carcinoma

Abstract Introduction: Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumours lacking a standardised timeline for treatment initiation post-diagnosis. Delays beyond 60 days are linked to poorer outcomes and higher recurrence risk. Methods: A retrospective review was conducted on patients over 18 with HNSCC treated with (chemo)radiation at a rural tertiary care centre (September 2020–2022). Data on patient demographics, oncologic characteristics, treatment details and delay causes were analysed using SPSS. Results: Out of 93 patients, 35.5% experienced treatment initiation delays (TTIs) over 60 days. Median TTI was 73 days for delayed cases, compared to 41.5 days otherwise. No significant differences in demographics or cancer characteristics were observed between groups. The primary reasons for the delay were care coordination (69.7%) and patient factors (18.2%). AJCC cancer stage showed a trend towards longer delays in advanced stages. Conclusion: One-third of patients faced delayed TTI, primarily due to care coordination and lack of social support. These findings highlight the need for improved multidisciplinary communication and patient support mechanisms, suggesting potential areas for quality improvement in HNSCC treatment management.

Frailty and Increased Levels of Symptom Burden Can Predict the Presence of Each Other in HNSCC Patients.

Frailty is an important risk factor for adverse events (AEs), especially in elderly patients. Therefore, assessing frailty before therapy is recommended. In head and neck squamous cell carcinoma (HNSCC) patients, frailty is prognostic for severe postoperative complications and declining quality of life (QoL) after HNSCC treatment. Thus, assessment of frailty may help to identify individuals at risk for AE caused by oncologic therapy. We investigated the relationship between frailty and symptom burden to better understand their interaction and impact on HNSCC patients. In this prospectively designed cross-sectional study, the presence of frailty and symptom burden was assessed by using the Geriatric 8 (G8) and Minimal Documentation System (MIDOS2) questionnaires. A total of 59 consecutively accrued patients with a first diagnosis of HNSCC before therapy were evaluated. Patients were considered frail at a total G8 score ≤ 14. The MIDOS2 symptom burden score was considered pathological with a total score ≥ 4 or any severe symptom (=3). Statistical correlations were analyzed using Spearman and Pearson correlation. Receiver operator characteristic (ROC) curves were used to analyze the potential of predicting frailty and MIDOS2. p-values < 0.05 were considered significant. A total of 41 patients (69.5%) were considered frail, and 27 patients (45.8%) had increased symptom burden. "Tiredness" was the most common (overall rate 57.8%) and "Pain" was the most often stated "severe" symptom (5 patients, 8.5%). G8 and MIDOS2 correlated significantly (ρ = -0.487, p < 0.001; r = -0.423, p < 0.001). Frailty can be predicted by MIDOS2 symptom score (AUC = 0.808, 95% CI 0.698-0.917, p < 0.001). Vice versa, the G8 score can predict pathological symptom burden according to MIDOS2 (AUC = 0.750, 95% CI 0.622-0.878, p < 0.001). Conclusions: The strong link between frailty and increased symptom burden assessed by G8 or MIDOS2 indicates a coherence of both risk factors in HNSCC patients. Considering at least one of both scores might improve the identification of individuals at risk and achieve higher QoL and reduced complication rates by decision making for appropriate therapy regimens.

SENP1 inhibits ferroptosis and promotes head and neck squamous cell carcinoma by regulating ACSL4 protein stability via SUMO1.

Head and neck squamous cell carcinoma (HNSCC) is currently one of the most common malignancies with a poor prognosis worldwide. Meanwhile, small ubiquitin‑like modifier (SUMO) specific peptidase1 (SENP1) was associated with ferroptosis. However, the specific functions and underlying mechanisms of action of SENP1 in ferroptosis and tumor progression of HNSCC remain to be established. The findings of the present study implicated a novel ferroptosis pathway in the initiation and progression of HNSCC, providing new functional targets to guide future therapy. In the present study, The Cancer Genome Atlas database was employed to establish a gene model related to ferroptosis and verified SENP1 as a key gene via transcriptome sequencing. Expression of SENP1 in HNSCC tissue and CAL‑27cells was detected based on reverse transcription‑quantitative PCR and western blot analysis. Proliferation and migration abilities of cells were determined using Cell Counting Kit‑8, wound healing and Transwell experiments. Expression levels of iron, glutathione (GSH) and lipid peroxidation end‑product malondialdehyde (MDA) under conditions of silencing of SENP1 with shRNA lentivirus were assayed. Additionally, the relationship between SENP1 and long‑chain acyl‑coenzyme A synthase 4 (ACSL4) was validated with the aid of immunoblotting and co‑immunoprecipitation (co‑IP). Finally, the influence of shSENP1 on the expression of key ferroptosis proteins, glutathione peroxidase4 (GPX4) and solute carrier family7 member11, was evaluated via western blotting. It was revealed that SENP1 was significantly overexpressed in HNSCC and associated with low patient survival. Silencing of SENP1 led to significant suppression of cell proliferation, migration and invasion, increase in the contents of iron ions and MDA and decline in GSH levels in HNSCC cells, thereby enhancing ferroptosis and inhibiting disease progression. Conversely, overexpression of SENP1 suppressed ferroptosis and promoted progression of HNSCC. Co‑IP and western blot analyses revealed a SUMOylation link between SENP1 and ACSL4. SENP1 reduced the stability of ACSL4 protein through deSUMOylation, leading to inhibition of ferroptosis. SENP1 silencing further inhibited the expression of the key iron death protein, GPX4, to regulate ferroptosis. Taken together, SENP1 deficiency promoted ferroptosis and inhibited tumor progression through reduction of SUMOylation of ACSL4 in HNSCC. The collective results of the present study supported the utility of SENP1 as an effective predictive biomarker for targeted treatment of HNSCC.

Immunotherapy for head and neck squamous cell carcinoma: current status and perspectives.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of several solid cancers, including head and neck squamous cell carcinoma (HNSCC). First approved for second-line settings, ICIs are now used for the first-line treatment of HNSCCs, mainly in combination with standard chemotherapy. This review focuses on the results of themain phase III studies evaluating ICIs in recurrent or metastatic HNSCCs. Theefficacy and indications according to the PD-L1status, the main predictive biomarker, arediscussed. The results of trials assessing ICI efficacy for locally advanced disease, including the neoadjuvant setting are also discussed. Finally, therapeutic combinations that are potential treatments for HNSCCs, including ICIs and targeted therapies such as anti-EGFRagents, are presented.

Tumor-derived extracellular vesicles in the immune microenvironment of head and neck squamous cell carcinoma: Foe or future?

Head and neck squamous cell carcinoma (HNSCC) is considered a “cold tumor” due to its suppressive immune microenvironment, and is associated with a poor prognosis. Tumor-derived extracellular vesicles (EVs) play an essential role in the tumor microenvironment and mediate intercellular communications. EVs have been proven to be key immune regulators involved in antitumor immune responses and escape from immune surveillance. Tumor-derived EVs favor the formation of an immunosuppressive tumor microenvironment by regulating the differentiation, proliferation and activation of innate and adaptive immune effector cells, as well as myeloid cells, acting as a “foe” in the microenvironment. However, EVs are also valuable for predicting and improving the prognosis of HNSCC, and represent hope for future treatments. In this review, we summarize the impact of HNSCC-derived EVs on the immune microenvironment, describe their roles as biomarkers and for drug delivery in disease monitoring and treatment. We provide insights into important areas for future research and identify potential therapeutic targets for HNSCC treatment.

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.

Gold Nanoparticles Enhance the Tumor Growth-Suppressing Effects of Cetuximab and Radiotherapy in Head and Neck Cancer In Vitro and In Vivo

Introduction: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor (EGFR) and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity and induces serious side effects. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. Methods and Results: This study investigated the in vitro effects of single and combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on a human HNSCC cell line, HSC-3. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HSC-3 numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) of a xenograft model of HSC-3 cells transplanted into nude mice (BALB/cAJcl-nu/nu) reduced the tumor volume compared with the controls. Scanning electron microscopy demonstrated the presence of AuNPs in tumor tissues and toxicity analysis indicated that AuNPs had no toxic effect on normal tissues. Conclusions: This study showed that AuNPs alone do not have a tumor-suppressing effect, but they sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects.

Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response.

The 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately 65%. In addition to radio-chemotherapy, immunotherapy is an approach in the treatment of advanced HNSCC. A better understanding of the immune context would allow personalized treatment by identifying patients who are best suited for different treatment options. In our discovery cohort, we evaluated the expression profiles of CMTM6, PD-L1, CTLA-4, and FOXP3 in 177 HNSCCs from Caucasian patients of all tumor stages and different treatment regimens, correlating marker expression in tumor and immune cells with outcomes. Patients with CMTM6high-expressing tumors had a longer overall survival regardless of treatment. This prognostic benefit of CMTM6 in HNSCC was validated in an independent cohort. Focusing on the in the discovery cohort (n = 177), a good predictive effect of CMTM6high expression was seen in patients receiving radiotherapy (p = 0.07; log rank), but not in others. CMTM6 correlated with PD-L1, CTLA-4 and FOXP3 positivity, with patients possessing CMTM6high/FOXP3high tumors showing the longest survival regardless of treatment. In chemotherapy-treated patients, PD-L1 positivity was associated with longer progression-free survival (p < 0.05). In the 27 patients who received immunotherapy, gene expression analysis revealed lower levels of CTLA-4 and FOXP3 with either partial or complete response to this treatment, while no effect was observed for CMTM6 or PD-L1. The combination of these immunomodulatory markers seems to be an interesting prognostic and predictive signature for HNSCC patients with the ability to optimize individualized treatments.

Comprehensive analysis of single-cell and bulk RNA-sequencing data identifies B cell marker genes signature that predicts prognosis and analysis of immune checkpoints expression in head and neck squamous cell carcinoma

Recent studies have shown that B cells and the associated tertiary lymphoid structures (TLS) correlate with the response of patients to immune checkpoint inhibitors (ICIs) and predict overall survival (OS) in cancer patients. We screened 145 B cell marker genes (BCMG) by a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of head and neck squamous cell carcinoma (HNSC) from the Gene Expression Omnibus (GEO) database. The BCMG signature (BCMGS) was established using The Cancer Genome Atlas (TCGA) dataset of HNSC and verified in four independent datasets. The multivariate Cox regression analysis identified the signature as an independent prognostic factor. A prognostic nomogram was constructed with independent prognostic factors using the TCGA dataset. GO and KEGG analysis revealed the underlying signaling pathways related to this signature. Study of immune profiles showed that patients in the low-risk group presented discriminative immune-cell infiltrations. Furthermore, the low-risk group was featured by higher TCR and BCR diversity, which suggested that low-risk patients may be more sensitive to ICIs. Immunohistochemistry was performed, and we found that high expression of FTH1 was significantly correlated with poor OS (P = 0.025). The expression of TIM-3, LAG-3 and PD-1 was positively correlated and associated with better OS in HNSC. However, there was no statistically significant difference between PD-L1, PD-L2, CTLA-4, TIGIT and prognosis. The BCMGS was a promising prognostic biomarker in HNSC, which may help to interpret the responses to immunotherapy and provide a new perspective for future research on the treatment in HNSC.

Involvement of the OTUB1-YAP1 axis in driving malignant behaviors of head and neck squamous cell carcinoma.

Comprehending the molecular mechanisms underlying head and neck squamous cell carcinoma (HNSCC) is vital for the development of effective treatment strategies. Deubiquitinating enzymes (DUBs), which regulate ubiquitin-dependent pathways, are potential targets for cancer therapy because of their structural advantages. Here we aimed to identify a potential target for HNSCC treatment among DUBs. A screening process was conducted using RNA sequencing data and clinical information from HNSCC patients in the TCGA database. A panel of 88 DUBs was analyzed to identify those associated with poor prognosis. Subsequently, HNSCC cells were modified to overexpress specific DUBs, and their effects on cell proliferation and invasion were evaluated. Invivo experiments were performed to validate the findings. In HNSCC patients, USP10, USP14, OTUB1, and STAMBP among the screened DUBs were associated with a poor prognosis. Among them, OTUB1 showed the most aggressive characteristics in both invitro and invivo experiments. Additionally, OTUB1 regulated the stability and nuclear localization of YAP1, a substrate involved in cell proliferation and invasion. Notably, OTUB1 expression exhibited a positive correlation with the HNSCC-YAP score in HNSCC cells. This study highlights the critical role of OTUB1 in HNSCC progression via modulating YAP1. Targeting the OTUB1-YAP1 axis holds promise as a potential therapeutic strategy for HNSCC treatment.

Unveiling the potential of angiotensin-converting enzyme as a therapeutic target in head and neck squamous carcinoma

This study investigated the effects of ACE inhibition on Head and Neck Squamous Cell Carcinoma (HNSCC), tumor progression, and the relation of ACE2, AGTR1, ACE, and MAS1 expression with HNSCC patient` survival. ACE inhibitor (Captopril) treatment was applied into Swiss male mice. ACE2, AGTR1, ACE, and MAS1 expression levels were analyzed in HNSCC tumor tissues from The Cancer Genome Atlas (TCGA) database. ACE inhibition reduced cell viability, proliferation, migration, and invasion, increased ROS levels, and induced apoptosis in SCC9 cells. Neoplastic angiogenesis was suppressed by ACE inhibition in the CAM assay. ACE inhibition also reduced the incidence of severe dysplasia/carcinoma in the histological analysis. TCGA data revealed that lower ACE2 levels were associated with poorer survival outcomes, while increased AGTR1 expression correlated with a higher risk of death in HPV-negative patients. ACE upregulation and higher MAS1 expression were observed in HNSCC tumor tissues. ACE inhibition demonstrated anti-cancer effects in HNSCC cells and suppressed neoplastic angiogenesis. It also reduced histological aggressiveness and showed potential predictive value for ACE2 and AGTR1 expression levels in HNSCC. These findings suggest the therapeutic potential of ACE inhibitors in HNSCC treatment, requiring further investigation and validation in clinical settings.

Head and Neck Squamous Cell Carcinoma Vaccine: Current Landscape and Perspectives.

The treatment of unresectable or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) has traditionally relied on chemotherapy or radiotherapy, yielding suboptimal outcomes. The introduction of immunotherapy has significantly improved HNSCC treatment, even if the long-term results cannot be defined as satisfactory. Its mechanism of action aims to counteract the blockade of tumor immune escape. This result can also be obtained by stimulating the immune system with vaccines. This review scope is to comprehensively gather existing evidence and summarize ongoing clinical trials focused on therapeutic vaccines for HNSCC treatment. The current landscape reveals numerous promising drugs in the early stages of experimentation, along with a multitude of trials that have been suspended or abandoned for years. Nonetheless, there are encouraging results and ongoing experiments that instill hope for potential paradigm shifts in HNSCC therapy.

CD44v6 specific CAR-NK cells for targeted immunotherapy of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a major challenge for current therapies. CAR-T cells have shown promising results in blood cancers, however, their effectiveness against solid tumors remains a hurdle. Recently, CD44v6-directed CAR-T cells demonstrated efficacy in controlling tumor growth in multiple myeloma and solid tumors such as HNSCC, lung and ovarian adenocarcinomas. Apart from CAR-T cells, CAR-NK cells offer a safe and allogenic alternative to autologous CAR-T cell therapy. In this paper, we investigated the capacity of CAR-NK cells redirected against CD44v6 to execute cytotoxicity against HNSCC. Anti-CD44v6 CAR-NK cells were generated from healthy donor peripheral blood-derived NK cells using gamma retroviral vectors (gRVs). The NK cell transduction was optimized by exploring virus envelope proteins derived from the baboon endogenous virus envelope (BaEV), feline leukemia virus (FeLV, termed RD114-TR) and gibbon ape leukemia virus (GaLV), respectively. BaEV pseudotyped gRVs induced the highest transduction rate compared to RD114-TR and GaLV envelopes as measured by EGFP and surface CAR expression of transduced NK cells. CAR-NK cells showed a two- to threefold increase in killing efficacy against various HNSCC cell lines compared to unmodified, cytokine-expanded primary NK cells. Anti-CD44v6 CAR-NK cells were effective in eliminating tumor cell lines with high and low CD44v6 expression levels. Overall, the improved cytotoxicity of CAR-NK cells holds promise for a therapeutic option for the treatment of HNSCC. However, further preclinical trials are necessary to test in vivo efficacy and safety, as well to optimize the treatment regimen of anti-CD44v6 CAR-NK cells against solid tumors.

The Prognostic Value of Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio, and Monocyte-Lymphocyte Ratio in Head and Neck Squamous Cell Carcinoma (HNSCC)-A Retrospective Single Center Study and a Literature Review.

Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and pallets-to-lymphocyte ratio (PLR) are currently validated as cheap and accessible biomarkers in different types of solid tumors, including head and neck cancers (HNC). To evaluate the possible purposes and biomarker value of NLR, PLR, and MLR recorded pre-treatment (radiotherapy/chemotherapy) in HNC. From 190 patients with HNC included in the oncology records in the oncology outpatient clinic of the Craiova County Emergency Hospital (from January 2002 to December 2022), 39 cases met the inclusion criteria (squamous cell carcinoma and the possibility to calculate the pre-treatment (chemotherapy/radiotherapy) value of NLR, PLR, and MLR. Overall survival (OS) values were correlated with NLR, PLR, and MLR. The median values for NLR, PLR, and MLR were 6.15 (1.24-69), 200.79 (61.3-1775.0), and 0.53 (0.12-5.5), respectively. In the study, the mean values for NLR, PLR, and MLR of 2.88, 142.97, and 0.36, respectively, were obtained. The median OS in the study group was 11 months (1-120). Although a negative Pearson's correlation was present, the relationship between the variables was only weak, with values of R = 0.07, p = 0.67, R = 0.02, p = 0.31, and R = 0.07, p = 0.62 being related to NLR, PLR, and MLR, respectively, in correlation with OS. The median values of NLR, PLR, and MLR were calculated (1.53, 90.32, and 0.18, respectively) for the HNC cases with pre-treatment values of NLR < 2 and for the HNC cases with NLR values ≥ 6 (23.5, 232.78, and 0.79, respectively). The median OS for cases with NLR < 2 and NLR ≥ 6 were 17.4 and 13 months, respectively. The comparative analysis of the data highlights a benefit to OS for cases low values of NLR. The role of not only borderline NLR values (between 2 and 6) as a prognostic marker in HNSCC but also the inclusion of PLR and MLR in a prognostic score must also be defined in the future. Prospective studies with more uniformly selected inclusion criteria could demonstrate the value of pre-treatment NLR, PLR, and MLR for treatment stratification through the intensification or de-escalation of non-surgical curative treatment in HNSCC.

Competing endogenous RNAs in head and neck squamous cell carcinoma: a review.

Our understanding of RNA biology has evolved with recent advances in research from it being a non-functional product to molecules of the genome with specific regulatory functions. Competitive endogenous RNA (ceRNA), which has gained prominence over time as an essential part of post-transcriptional regulatory mechanism, is one such example. The ceRNA biology hypothesis states that coding RNA and non-coding RNA co-regulate each other using microRNA (miRNA) response elements. The ceRNA components include long non-coding RNAs, pseudogene and circular RNAs that exert their effect by interacting with miRNA and regulate the expression level of its target genes. Emerging evidence has revealed that the dysregulation of the ceRNA network is attributed to the pathogenesis of various cancers, including the head and neck squamous cell carcinoma (HNSCC). This is the most prevalent cancer developed from the mucosal epithelium in the lip, oral cavity, larynx and pharynx. Although many efforts have been made to comprehend the cause and subsequent treatment of HNSCC, the morbidity and mortality rate remains high. Hence, there is an urgent need to understand the holistic progression of HNSCC, mediated by ceRNA, that can have immense relevance in identifying novel biomarkers with a defined therapeutic intervention. In this review, we have made an effort to highlight the ceRNA biology hypothesis with a focus on its involvement in the progression of HNSCC. For the identification of such ceRNAs, we have additionally highlighted a number of databases and tools.

Diagnostic accuracy of NI-RADS for prediction of head and neck squamous cell carcinoma: a systematic review and meta-analysis.

This study aimed to assess the diagnostic performance of NI-RADS for the prediction of recurrence in patients treated for Head and Neck Squamous Cell Carcinoma (HNSCC). A literature search was conducted using various databases to identify relevant articles published from June 2016 onwards. We included studies reporting the diagnostic accuracy of NI-RADS in distinguishing recurrence in patients undergoing imaging surveillance, with pathologic results and/or follow-up as the reference standard. Summary estimates of diagnostic accuracy in terms of sensitivity, specificity, positive likelihood ratio (LR +), negative likelihood ratio (LR -), and diagnostic odds ratio (DOR) were calculated with the hierarchical summary receiver operating characteristic (HSROC) model. Meta-regression and subgroup analyses were conducted to investigate different clinical settings. Study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 12 studies were included in the current meta-analysis. The pooled sensitivity and specificity were 0.69 (95% CI 0.59-0.79) and 0.94 (95% CI 0.89-0.97), respectively. For the primary site, the pooled summary estimates were 0.67 (95% CI 0.53-0.78) and 0.95 (95% CI 0.90-0.97), for the nodal sites were 0.64 (95% CI 0.44-0.80) and 0.99 (95% CI 0.98-0.99), respectively. The recurrence rate for NI-RADS categories 1-3 was 0.03 (95% CI 0.02-0.05), 0.13 (95% CI 0.10-0.15), and 0.77 (95% CI 0.73-0.81). Meta-regression revealed that the type of analysis (per person vs. per site) and number of sites (≤ 200 vs. > 200) were significant factors associated with heterogeneity. NI-RADS demonstrated high specificity but moderate sensitivity in patients after treatment for HNSCC. Summary estimates showed a significantly higher malignancy rate for NI-RADS category 3 compared to category 2.

Review of RM-1929 Near-Infrared Photoimmunotherapy Clinical Efficacy for Unresectable and/or Recurrent Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) contribute to a significant global cancer burden. Developments in current therapeutic approaches have improved patient outcomes but have limited efficacy in patients with unresectable and/or recurrent HNSCC. RM-1929 near-infrared photoimmunotherapy (NIR-PIT) is an emerging treatment that is currently being investigated in a Phase III clinical trial and has been conditionally approved for the treatment of unresectable and/or recurrent HNSCC in Japan. Here, we collect a series of case reports and clinical trial data to assess the efficacy of RM-1929 NIR-PIT. Disease control rates ranged from 66.7 to 100% across these studies, and overall response rates ranged from 43.3 to 100%, suggesting positive clinical outcomes. Low-grade postoperative localized pain and edema were the most frequently reported side effects, and preliminary reports on quality of life and pain levels suggest that RM-1929 NIR-PIT does not significantly decrease quality of life and is manageable with existing pain management strategies, including opioids. These preliminary data in real-world use of RM-1929 NIR-PIT show that it is a well-tolerated therapy that has clinically meaningful outcomes for patients with unresectable and/or recurrent HNSCC.