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Objective: Iodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining. Methods: Twenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow-band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging. Result: The median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow-band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01). Conclusions: The visibility of ESCC after iodine staining was greater on TXI than on WLI.

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Objectives: Endoscopic treatment of superficial pharyngeal carcinomas includes endoscopic submucosal dissection (ESD; usually performed by endoscopists), and endoscopic laryngo-pharyngeal surgery (ELPS; primarily performed by otolaryngologists). Few studies have compared the efficacy of the two techniques in treating superficial pharyngeal carcinomas. In this study, we compared the outcomes of these two techniques to determine the advantages. Methods: We retrospectively examined the short- and long-term outcomes of 93 consecutive patients with superficial pharyngeal carcinoma who either underwent an ESD or ELPS between August 2008 and December 2021. Results: There were 35 lesions among 29 patients and 93 lesions among 71 patients in the ESD and ELPS groups, respectively. The ELPS group had a significantly shorter procedure time (121.2 ± 97.4 min vs. 54.7 ± 40.2 min, p<0.01), greater procedure speed (0.10 ± 0.06 min/min vs. 0.30 ± 0.23 min/min, p<0.01), and less laryngeal edema than that of the ESD group. There were no significant differences in the 3-year overall, relapse-free, or disease-specific survival rates between the two groups. Intervention with ESD during ELPS was most commonly required when it was difficult to secure the visual field. Conclusions: There were no differences in batch resection rates or long-term prognoses between the two groups; nevertheless, the ELPS group had a shorter treatment time and less laryngeal edema than the ESD group. However, the treatment of narrow areas, such as the esophageal inlet patch, is a technical limitation of ELPS; thus, ELPS should be combined with ESD techniques.

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OBJECTIVES: The renin-angiotensin system (RAS) plays essential roles in cardiovascular and renal function regulation. Recent studies have shown that the RAS components are widely expressed in oral tissues, but their roles in oral diseases remain underexplored. This review aims to summarize the effects of the RAS in select oral diseases including oral squamous cells carcinoma (OSCC), periodontitis, oral submucous fibrosis (OSF), and ageusia/dysgeusia. SUBJECTS AND METHODS: Data searches were performed using PubMed, Web of Science and Scopus through July 2024. A narrative overview of current literature was undertaken to synthesize the contexts with elaboration and summary. RESULTS: In OSCC, ACE/Ang II/AT1R promotes OSCC by inducing angiogenesis, cell proliferation and invasiveness. Conversely, ACE/Ang II/AT2R and ACE2/Ang (1-7)/MasR inhibit OSCC progressions. In periodontitis, ACE/Ang II/AT1R upregulates inflammatory cytokines and promotes osteoclast differentiation factor RANKL, whereas ACE2/Ang (1-7)/MasR exerts opposite effects by preventing inflammation and alveolar bone loss. In OSF, Ang (1-7) counters the profibrotic and proinflammatory action of Ang II. In dysgeusia, Ang II suppresses salt taste responses and enhances sweet taste sensitivities, while Ang (1-7) exhibits opposite effects. CONCLUSIONS: The RAS cascade plays crucial roles in OSCC, periodontitis, OSF and ageusia/dysgeusia. The imbalanced RAS may aggravate the progression of these diseases.

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CLINICAL RELEVANCE: The role and prognostic significance of systemic inflammatory markers in various malignancies have been the subject of investigation. The role of these inflammatory markers in eyelid lesions remains to be elucidated. BACKGROUND: Benign and malignant lesions of the eyelid are common presentations in eye clinics. Systemic inflammatory markers derived from a complete blood count may provide insight into the benign-malignant differentiation of the lesion. METHODS: This study included 134 patients who underwent surgery for eyelid lesions between 2021-2023. The lesions were evaluated by oculoplastic surgeons and operated on with a preliminary diagnosis of benign or malignant. According to the histopathological diagnosis, benign lesions were included in Group 1 and malignant lesions in Group 2. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII) (NxP/L) based on neutrophil, lymphocyte, and platelet counts were calculated from the preoperative complete blood count of all patients. RESULTS: Eighty-eight patients were included in Group 1 and 46 patients in Group 2. There were 41/47 (Female/Male) in Group 1 and 19/27 (F/M) males in Group 2 (p = 0.345). The mean age was 62.91 ± 9.04 years in Group 1 and 65.41 ± 8.76 years in Group 2 (p = 0.127). The preliminary diagnosis and histopathological diagnosis were incompatible in 5 cases in both groups. In Group 1: NLR = 1.82 ± 0.72, PLR = 124.50 ± 45.19 and SII = 454.51 ± 220.20, in Group 2: NLR = 2.48 ± 0.89, PLR = 128.12 ± 49.58 and SII = 590.22 ± 271.09. NLR and SII differences between groups were statistically significant, while PLR was similar (p < 0.001, p = .002, p = .671). ROC curve analysis showed that the optimal cut-off values for NLR, PLR, and SII were 1.99, 119.16, and 475.21, respectively. CONCLUSION: High levels of NLR and SII in eyelid tumours can be used as an adjunct to examination findings in the preliminary diagnosis of the lesion as benign or malignant and may influence surgical planning.

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OBJECTIVE: Identifying the drive genes and inhibiting their significant signals were persistently the main concepts in cancer treatment. However, for oral cavity squamous cell carcinoma (OCSCC), the most influential genes for overall survival (OS) remain unclear. METHODS: A total of 120 OCSCC patients with corresponding pathologic specimens were collected in Taiwan. Whole-exome sequencing was done and the prognostic impact of each gene was analyzed. TCGA database was used to validate. RESULTS: The incidences of caspase-8 mutation were 22.1% and 10.9% in the Taiwan and TCGA cohort, respectively. In the Taiwan cohort, caspase-8 mutation was the most significant independent for OS with an adjusted hazard ratio (HR) ([95% CI]: 3.83 [1.84-7.99]). It was validated by the TCGA database (HR [95% CI]: 1.51 [1.00-2.29]). The 5-year OSs of the patients with or without caspase-8 mutation were 38.1% vs. 75.3% (p < 0.001) (HR [95% CI]: 3.264 [1.645-6.438]) in the Taiwan cohort, and 26.1% vs. 49.0% (p = 0.048) (1.513 [1.001-2.288]) in the TCGA cohorts, respectively. Caspase-8 mutation was also individually associated with poor prognosis for TNM stage I/II/III/IV, respectively. CASP8 R127* and R494*, defined as pathogenic mutations in ClinVar, were presented in both cohorts. CONCLUSIONS: Caspase-8 mutation was the most significant genetic alteration impacting prognosis.

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BACKGROUND: Prunellae Spica (PS), the spike from Prunella vulgaris L., is a traditional Chinese medicine that can treat Oral Squamous Cell Carcinoma (OSCC), whereas its molecular mechanisms and effects on the prognosis of patients remain unclear. METHODS: Our study aimed to identify potential anti-OSCC targets of PS and explore its mechanisms and effects on prognosis through network pharmacology, bioinformatics analysis, molecular docking, and in vitro cell assays. RESULTS: Sixty-two potential targets of 11 active anti-OSCC ingredients of PS were identified, with Quercetin, the core ingredient of PS, exhibiting the most significant number of OSCC-related targets. GO analysis indicated that the primary biological processes involved in OSCC treatment by PS were the cellular response to nitrogen compound, response to xenobiotic stimulus, and cellular response to organonitrogen compound. KEGG analysis revealed that Pathways in cancer were the top highly enriched signaling pathway in the treatment of OSCC by PS. DisGeNET analysis is mainly about Lip and Oral Cavity Carcinoma. More importantly, 6 of the 62 targets were markedly related to prognosis. Molecular docking revealed high affinities between the key component and the prognosis-related target proteins. Treatment of OSCC cell line SCC-25 with Quercetin could inhibit malignant biological behaviors, such as cell proliferation, colony formation, invasion, and migration, as well as affect the targets related to prognosis and promote autophagy. CONCLUSION: Overall, these results suggest that PS plays a significant role in treating and improving the prognosis of OSCC by directly influencing various processes in OSCC.

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In management of oral squamous cell carcinoma (OSCC), only a few biomarkers, ranging from clinical and histopathological features to molecular alterations, have been demonstrated to have clinical and prognostic utility. The intent of this narrative review is to present current findings on the use of salivary microRNAs (miRNAs) as prognostic oncologic biomarkers in patients with OSCC. The ability to predict survival or recurrence during follow-up by quantification of specific miRNAs in saliva has been shown in a number of studies, and serves as a possible feature to address in future well-designed clinical studies to confirm their prognostic value. The non-invasiveness of liquid biopsy techniques, the ease of saliva collection, and the abundance and stability of miRNAs in such a biologic fluid make it an attractive combination to improve management of OSCC. For salivary miRNAs to be used in routine practice, however, methodological and sampling standardisation are still needed to increase the power and accuracy of the results obtained.

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OBJECTIVES: This case study evaluated the efficacy of mid-infrared spectroscopy on the identification of oral squamous cell carcinoma, following the assessment of unstimulated whole saliva. STUDY DESIGN AND METHODS: The trial follows a matched case-control design. Saliva samples were characterized through mid-infrared spectroscopy, and chemometric tools were applied to distinguish between case and control participants, further identifying the spectral regions that played a pivotal role in the successful identification of oral squamous cell carcinoma. RESULTS: Mid-infrared spectroscopy was capable to discriminate between cancer patients and matched controls with 100% of correct predictions. Additionally, the spectral regions mostly contributing to the successful prediction were identified and found to be potentially associated with significant molecular changes crucial to the carcinogenic process. CONCLUSION: The application of mid-infrared spectroscopy in saliva analysis may be regarded as an innovative, noninvasive, low cost, and sensitive technique contributing to the identification of oral squamous cell carcionma.

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Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma. A total of 105 patients with stage 1 glottic squamous cell carcinoma underwent definitive radiotherapy alone between 2007 and 2021. The group in which radiotherapy was started between Monday and Wednesday was compared with the group in which radiotherapy was started on Thursday or Friday. Sixty-seven patients started radiotherapy between Monday and Wednesday and 38 on Thursday or Friday. The 5-year local control rate was 98% (95% confidence interval: 94-100%) in the Monday-Wednesday group and 83% (95% confidence interval: 71-96%) in the Thursday-Friday group, with a significant difference (P = 0.005). On multivariate analysis including age, overall administration time (days), fractionation, irradiation field size and initiation weekday of radiotherapy, no factors other than initiation weekday affecting local control were identified. Radiotherapy toxicity did not differ between the two groups. For stage 1 glottic squamous cell carcinoma, starting radiotherapy on Thursday or Friday is associated with a lower local control rate; therefore, radiotherapy should be started by Wednesday.

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BACKGROUND: This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) vs. CCRT alone in patients with non-operable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between 2008 and 2022, 271 ESCC patients who received definitive CCRT based on intensity modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) were enrolled. Through a propensity score-matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. RESULTS: The IC + CCRT group had no improvement in 5-year overall survival (OS) rate, recurrence-free survival (RFS) rate, and distant metastasis-free survival (DMFS) rate (all p > 0.05) compared with the CCRT group. The 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders were significantly higher than that of the IC poor responders and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and stage III/IV were independent predictive factors of OS, RFS, and DMFS. No significant differences were observed in the rates of grade 3-4 toxicities between both groups. CONCLUSIONS: Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without an increase in toxicities.

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BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascularity, which depends on the process of angiogenesis and affects tumour response to treatment. Our study explored the associations between DCE-MRI parameters and the expression of plasma angiogenic factors in human papilloma virus (HPV)-negative oropharyngeal cancer, as well as their predictive value for response to concurrent chemoradiotherapy (cCRT). PATIENTS AND METHODS: Twenty-five patients with locally advanced HPV-negative oropharyngeal carcinoma were prospectively enrolled in the study. DCE-MRI and blood plasma sampling were conducted before cCRT, after receiving a radiation dose of 20 Gy, and after the completion of cCRT. Perfusion parameters ktrans, kep, Ve, initial area under the curve (iAUC) and plasma expression levels of angiogenic factors (vascular endothelial growth factor [VEGF], connective tissue growth factor [CTGF], platelet-derived growth factor [PDGF]-AB, angiogenin [ANG], endostatin [END] and thrombospondin-1 [THBS1]) were measured at each time-point. Patients were stratified into responders and non-responders based on clinical evaluation. Differences and correlations between measures were used to generate prognostic models for response prediction. RESULTS: Higher perfusion parameter ktrans and higher plasma VEGF levels successfully discriminated responders from non-responders across all measured time-points, whereas higher iAUC and higher plasma PDGF-AB levels were also discriminative at selected time points. Using early intra-treatment measurements of ktrans and VEGF, a predictive model was created with cut-off values of 0.259 min-1 for ktrans and 62.5 pg/mL for plasma VEGF. CONCLUSIONS: Early intra-treatment DCE-MRI parameter ktrans and plasma VEGF levels may be valuable early predictors of response to cCRT in HPV-negative oropharyngeal cancer.

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This systematic review aims to highlight the molecular mechanisms by which whole cigarette smoke affects oral carcinogenesis and its progression in human oral cells, based on evidence from original research articles published in the literature. A literature search was conducted using three databases: Web of Science, Scopus, and PubMed from May to June 2024. The articles were screened, and the data were extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (2020). The included studies were subsequently evaluated using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool for bias factors. From the 14 included studies, two types of cell lines were frequently utilized: human oral mucosal epithelial cells or oral squamous cell carcinoma cells. In these cell lines, one of three forms of exposure was applied: cigarette smoke, its extract, or condensate. The mechanism of oral carcinogenesis and tumor progression includes aberrations in the heme metabolic pathway, modulation of miRNA-145, NOD1 and BiP expression, MMP-2, MMP-9, and cathepsin modulation, abnormal TSPO binding, RIP2-mediated NF-κB activation, MZF1-mediated VEGF binding, and activation of the RAGE signaling pathway. In conclusion, cigarette smoke significantly influences the development and progression of oral squamous cell carcinoma, based on the evidence highlighted in human oral cells. While previous studies have focused on specific carcinogens and pathways, this review added to our understanding of the overall impact of whole cigarette smoke on oral carcinogenesis at the molecular and cellular levels.

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A 73-year-old male presented with a lower lip squamous cell carcinoma (SCC) (23 mm in diameter). Systemic imaging, including computed tomography (CT) and positron emission tomography, showed no evidence of distant metastasis. Due to the large size of the tumor, reconstruction after surgical tumor removal was considered to be difficult. Therefore, we decided to initially perform intra-arterial chemotherapy. Under local anesthesia, a catheter was inserted via the femoral artery. CT aortography from the ascending aorta was performed to visualize the precise vascular anatomy. The tumor's feeding arteries were confirmed by injecting indigo carmine dye through the catheter. Then, 87.5 mg of cisplatin was selectively injected through the left and right facial arteries (total dose of 175 mg). The tumor significantly shrank and almost disappeared 1 month after chemotherapy. Although additional intra-arterial chemotherapy was considered, the risks associated with the procedure meant that radiotherapy was performed instead. There were no signs of recurrence at the 2-year follow-up. In this patient, a single intra-arterial infusion chemotherapy combined with radiotherapy achieved complete disappearance of a large SCC of the lower lip. This treatment strategy allowed us to preserve the functional and cosmetic aspects of the patient's lower lip with minimal side effects. CT aortography and dye infusion were important in confirming the tumor's feeding arteries.

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Sinonasal tumors are often malignant and comprise approximately 3% of all head and neck malignancies. Half of these tumors arise in the nasal cavity, and other common locations of origin include the ethmoid and maxillary sinuses. Some unique clinical features are anosmia and altered phonation but the most common general features include headache, epistaxis, and diplopia. CT and MRI may be used to assess tumor location, invasion of adjacent tissue, presence of metastasis, internal tumor heterogeneity, and contrast enhancement. Local invasion of the tumor beyond the sinonasal tract can impact adjacent structures such as the cranial nerves, skull base, branches of the internal carotid artery, and orbit leading to neurologic signs, facial pain, and diplopia. Imaging is used in the diagnosis, staging, and treatment planning of sinonasal tumors. This collection of benign and malignant sinonasal tumors will include some rare and unique cases with an emphasis on imaging features demonstrating a wide variety of pathologies.

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Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036). Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

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Background: Our previous research showed that Porphyromonas gingivalis (P. gingivalis) infection can activate the inflammatory signaling pathway and promotes the malignancy development of esophageal squamous cell carcinoma (ESCC). However, the prognostic significance of inflammatory response-related genes (IRRGs) in P. gingivalis-infected ESCC requires further elucidation. Hence, our study constructed a prognostic signature based on P. gingivalis and IRRGs to forecast the survival of patients with ESCC, which may provide insight into new treatment options for ESCC patients. Methods: Differentially expressed genes (DEGs) were identified in P.gingivalis-infected and P.gingivalis-uninfected ESCC cell by RNA sequencing. A risk model was constructed and validated using the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database by using univariate Cox regression analysis, LASSO, and the multivariate Cox regression analysis. Kaplan-Meier analysis was carried out to compare the overall survival (OS) between high-risk and low-risk groups. Single-sample gene set enrichment analysis was used to analyze the immune cell infiltration. The Genomics of Drug Sensitivity in Cancer database was used to predict drug sensitivity. Results: There were 365 DEGs between the P.gingivalis-infected and P.gingivalis-uninfected groups. Four genes including DKK1, ESRRB, EREG, and RELN were identified to construct the prognostic risk model (P = .012, C-index = 0.73). In both the training and validation sets, patients had a considerably shorter OS in the high-risk group than those in the low-risk group (P < .05). A nomogram was established using the risk score, gender, and N stage which could effectively forecast the prognosis of patients (P = .016, C-index = 0.66). The high-risk group displayed lower immune infiltrating cells, such as activated dendritic cells, type 2 T helper cells, and neutrophils (P < .05). A total of 41 drugs, including dactinomycin, luminespib, and sepantronium bromide, had a significant difference in IC50 between the 2 subgroups. Conclusion: We demonstrated the potential of a novel signature constructed from 4 P. gingivalis-related IRRGs for prognostic prediction in ESCC patients.

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Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

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In their letter-to-the-editor entitled "Letter to the Editor: Incidence rate of occult lymph node metastasis in clinical T1 - 2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study", Prof. Chen et al. provided insightful comments and suggestions on our original study. We appreciate the authors' feedback and have conducted a preliminary exploration of the predictive value of serum tumor markers (TMs) for occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients. The results indicate that neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), and squamous cell carcinoma antigen (SCC) have potential predictive value for detecting OLM in cT1 - 2N0M0 SCLC patients. Additionally, further exploration and confirmation through prospective, large-scale studies with robust external validation are needed.

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Head and neck squamous cell carcinoma (HNSC) represents nearly 90% of all head and neck tumors. The current treatment modality for HNSC patients primarily involves surgical intervention and radiotherapy, but its therapeutic efficacy remains limited. The mRNA vaccine based on tumor antigens seems promising for cancer treatment. Ferroptosis, a novel form of cell death, is linked to tumor progression and cancer immunotherapy. Nevertheless, the effectiveness of ferroptosis-associated tumor antigens in treating HNSC remains uncertain. In this study, we identified three ferroptosis-associated tumor antigens, namely caveolin1 (CAV1), ferritin heavy chain (FTH1), and solute carrier 3A2 (SLC3A2), as being overexpressed and mutated based on data obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. These antigens were strongly associated with poor prognosis and infiltration of antigen-presenting cells in HNSC. We further identified two ferroptosis subtypes (FS1 and FS2) with distinct molecular, cellular, and clinical properties to identify antigen-sensitive individuals. Our findings indicate that FS1 exhibits an immune "hot" phenotype, whereas FS2 displays an immune "cold" phenotype. Additionally, differential expression of immunogenic cell death modulators and immune checkpoints was observed between these two immune subtypes. Further exploration of the HNSC's immune landscape revealed significant heterogeneity among individual patients. Our findings suggest that CAV1, FTH1, and SLC3A2 are potential targets to prevent HNSC in FS2 patients. Overall, our research reveals the potential of ferroptosis-associated mRNA vaccines for HNSC and identifies an effective patient population for vaccine treatment.