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Biomedicines
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Advances in Molecular Mechanisms of Head and Neck Cancers
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Advances in Molecular Mechanisms of Head and Neck Cancers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 12259

Special Issue Editors

Prof. Dr. Chih-Yen Chien

E-Mail Website
Guest Editor
1. Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
2. College of Medicine, Chang Gung University, Taoyuan City, Taiwan
Interests: HNSCC; nasopharyngeal carcinoma; oropharyngeal cancer; oral cancer; laryngeal cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pei-Jen Lou

E-Mail Website
Guest Editor
Department of Otolaryngology Head and Neck Surgery, National Taiwan University Hospital, Taipei, Taiwan
Interests: glycosylation in HNSCC; targeting G-quadruplex DNA for the diagnosis and treatment of cancer; oral cancer; oropharyngeal cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck squamous cell carcinoma (HNSCC) ranks as the world’s sixth most common cancer among male patients according to the GLOBOCAN 2020 database. The clinical outcomes for advanced-stage tumors remain unsatisfactory. Cisplatin, 5-FU and docetaxol are the most common chemotherapy agents for HNSCC; however, chemo-resistance is currently a major problem among patients with recurrent and metastatic disease (R/M disease). Checkpoint inhibitors can be applied for salvage in R/M disease according to the clinical trials Checkmate-141 and Keynote-048. Clinically, some patients demonstrate responses to checkpoint inhibitors, but a significant number of patients show progressive disease. There are several unique molecular features in these advanced, chemoresistant tumors, and some tumors are responsive to checkpoint inhibitors. For this Special Issue, we welcome submissions focusing on these molecular characters and highlighting new treatment strategies for HNSCC.

Prof. Dr. Chih-Yen Chien
Prof. Dr. Pei-Jen Lou
Guest Editors

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Keywords

  • HNSCC
  • nasopharyngeal carcinoma
  • oropharyngeal cancer
  • oral cancer
  • laryngeal cancer
  • hypopharyngeal cancer
  • checkpoint inhibitor recurrent and metastatic head and neck cancer

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Published Papers (6 papers)

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15 pages, 7882 KiB  
Article
Piperlongumine Induces Apoptosis and Cytoprotective Autophagy via the MAPK Signaling Pathway in Human Oral Cancer Cells
by Eun-Young Choi, Eun-Ji Han, Su-Ji Jeon, Sang-Woo Lee, Jun-Mo Moon, Soo-Hyun Jung and Ji-Youn Jung
Biomedicines 2023, 11(9), 2442; https://doi.org/10.3390/biomedicines11092442 - 1 Sep 2023
Cited by 2 | Viewed by 2044
Abstract
Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longum L.), is a natural alkaloid with pharmacological [...] Read more.
Oral cancer is a malignant tumor that primarily affects areas such as the lips, tongue, buccal mucosa, salivary gland, and gingiva and has a very high malignancy. Piperlongumine (PL), isolated from long pepper (Piper longum L.), is a natural alkaloid with pharmacological effects, such as anti-inflammatory and anti-atherosclerotic effects. The effect and mechanism of PL in oral cancer cell lines has not been explored. Therefore, this study aimed to investigate the mechanism of anticancer effects of PL in the human oral cancer cell lines MC-3 and HSC-4 in vitro. This study demonstrated that PL inhibits cell proliferation by inducing apoptosis and autophagy in human oral cancer cell lines, which was confirmed by the levels of apoptosis- and autophagy-related proteins through Western blotting. Moreover, the pharmacological blockade of autophagy activation by hydroxychloroquine (HCQ), an autophagy inhibitor, significantly improved PL-induced apoptosis in MC-3 cells, suggesting a cytoprotective effect. In addition, activation of the mitogen-activated protein kinase (MAPK) signaling pathway contributed to PL-induced apoptosis. Collectively, the study suggested that combining an autophagy inhibitor with PL treatment can exert effective anticancer properties in oral cancer cells by inducing apoptosis and cytoprotective autophagy via the JNK-mediated MAPK pathway. Full article
(This article belongs to the Special Issue Advances in Molecular Mechanisms of Head and Neck Cancers)
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14 pages, 1286 KiB  
Article
Prognostic Utility of Neck Lymph Node-to-Primary Tumor Standardized Uptake Value Ratio in Oral Cavity Cancer
by Kuo-Wei Ho, Ku-Hao Fang, Chang-Hsien Lu, Cheng-Ming Hsu, Chia-Hsuan Lai, Chun-Ta Liao, Chung-Jan Kang, Yuan-Hsiung Tsai, Ming-Shao Tsai, Ethan I. Huang, Geng-He Chang, Chien-An Ko, Ming-Hsien Tsai and Yao-Te Tsai
Biomedicines 2023, 11(7), 1954; https://doi.org/10.3390/biomedicines11071954 - 11 Jul 2023
Cited by 3 | Viewed by 1508
Abstract
We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received [...] Read more.
We investigated the prognostic utility of preoperative neck lymph node-to-primary tumor maximum standardized uptake value ratios (NTRs) in oral cavity squamous cell carcinoma (OSCC). We retrospectively reviewed the medical records of 141 consecutive patients who were diagnosed as having OSCC and had received fluorodeoxyglucose–positron emission tomography within 2 weeks prior to radical surgery between 2009 and 2018. To determine the optimal NTR cutoff, receiver operating characteristic analysis for overall survival (OS) was executed. The NTR’s prognostic value for disease-free survival (DFS) and OS were determined through Cox proportional hazards analysis and the Kaplan–Meier method. We determined the median (range) follow-up duration to be 35.2 (2.1–122.4) months. The optimal NTR cutoff was 0.273, and patients with a higher NTR (≥0.273) exhibited significantly worse DFS and OS (p = 0.010 and 0.003, respectively). A higher NTR (≥0.273) predicted poorer DFS (hazard ratio: 2.696, p = 0.008) and OS (hazard ratio: 4.865, p = 0.003) in multivariable analysis. We created a nomogram on the basis of the NTR, and it could accurately predict OS (concordance index: 0.774). Preoperative NTRs may be a useful prognostic biomarker for DFS and OS in patients with OSCC who have undergone surgery. NTR-based nomograms may also be helpful prognostic tools in clinical trials. Full article
(This article belongs to the Special Issue Advances in Molecular Mechanisms of Head and Neck Cancers)
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15 pages, 2391 KiB  
Article
Non-Homologous End-Joining Pathway Genotypes Significantly Associated with Nasopharyngeal Carcinoma Susceptibility
by Chia-Wen Tsai, Liang-Chun Shih, Wen-Shin Chang, Che-Lun Hsu, Jie-Long He, Te-Chun Hsia, Yun-Chi Wang, Jian Gu and Da-Tian Bau
Biomedicines 2023, 11(6), 1648; https://doi.org/10.3390/biomedicines11061648 - 6 Jun 2023
Cited by 11 | Viewed by 1601
Abstract
Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, [...] Read more.
Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype–phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity. Full article
(This article belongs to the Special Issue Advances in Molecular Mechanisms of Head and Neck Cancers)
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11 pages, 712 KiB  
Article
Statin Use Ameliorates Survival in Oral Squamous Cell Carcinoma—Data from a Population-Based Cohort Study Applying Propensity Score Matching
by Steffen Spoerl, Michael Gerken, René Fischer, Silvia Spoerl, Christian Kirschneck, Stefanie Wolf, Juergen Taxis, Nils Ludwig, Niklas Biermann, Torsten E. Reichert and Gerrit Spanier
Biomedicines 2023, 11(2), 369; https://doi.org/10.3390/biomedicines11020369 - 27 Jan 2023
Cited by 3 | Viewed by 2092
Abstract
The anti-cancer properties of statins have attracted much attention recently, but little is known about the prognostic role of statins in oral squamous cell carcinoma (OSCC). In a retrospective approach, we analyzed a population-based cohort of 602 OSCC patients with primary curative tumor [...] Read more.
The anti-cancer properties of statins have attracted much attention recently, but little is known about the prognostic role of statins in oral squamous cell carcinoma (OSCC). In a retrospective approach, we analyzed a population-based cohort of 602 OSCC patients with primary curative tumor resection to negative margins and concomitant neck dissection between 2005–2017. Long-term medication with statins was correlated with overall survival (OAS) as well as recurrence-free survival (RFS) using uni- and multivariable Cox regression. Additionally, propensity score matching was applied to adjust for confounders. Statin use was present in 96 patients (15.9%) at a median age of 65.7 years. Statin treatment correlated with ameliorated survival in multivariable Cox regression in the complete cohort (OAS: HR 0.664; 95% CI 0.467–0.945, p = 0.023; RFS: HR 0.662; 95% CI 0.476–0.920, p = 0.014) as well as matched-pair cohort of OSCC patients (OAS: HR 0.691; 95% CI 0.479–0.997, p = 0.048; RFS: HR 0.694; 95% CI 0.493–0.976, p = 0.036) when compared to patients not taking statins at time of diagnosis. These findings were even more pronounced by sub-group analysis in the matched-pair cohort (age < 70 years). These data indicate that statin use might ameliorate the oncological outcome in primarily resected OSCC patients, but prospective clinical trials are highly recommended. Full article
(This article belongs to the Special Issue Advances in Molecular Mechanisms of Head and Neck Cancers)
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12 pages, 1209 KiB  
Article
Low p16 Cytoplasmic Staining Predicts Poor Treatment Outcome in Patients with p16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving TPF Induction Chemotherapy
by Yen-Hao Chen, Chih-Yen Chien, Tai-Ling Huang, Tai-Jen Chiu, Yu-Ming Wang, Fu-Min Fang and Shau-Hsuan Li
Biomedicines 2023, 11(2), 339; https://doi.org/10.3390/biomedicines11020339 - 25 Jan 2023
Cited by 4 | Viewed by 2285
Abstract
Human papillomavirus (HPV) has been proven to be associated with head and neck squamous cell carcinoma (HNSCC), and diffuse p16 unclear staining is usually considered as HPV-positive. The aim of the current study was to investigate the role of p16 cytoplasmic staining in [...] Read more.
Human papillomavirus (HPV) has been proven to be associated with head and neck squamous cell carcinoma (HNSCC), and diffuse p16 unclear staining is usually considered as HPV-positive. The aim of the current study was to investigate the role of p16 cytoplasmic staining in HNSCC prognosis. A total of 195 HNSCC patients who received docetaxel, cisplatin, and 5-fluouracil (TPF) induction chemotherapy followed by chemoradiotherapy were enrolled. The status of p16 cytoplasmic staining was determined using immunohistochemistry. The median follow-up was 26.0 months for the whole study population and 90.3 months for 51 living survivors. p16 cytoplasmic staining was low in 108 patients and high in 87 patients. Low expression of p16 cytoplasmic staining and primary tumor location in the oral cavity were both independent factors indicating a worse response rate to TPF induction chemotherapy in the univariate and multivariate analyses. The logistic regression model also showed that low expression of p16 cytoplasmic staining and clinical N2–3 status were independent prognostic factors for worse progression-free survival and overall survival. Our study showed that p16 cytoplasmic staining could predict the treatment response to TPF induction chemotherapy and is an independent prognostic factor of survival in HNSCC. Full article
(This article belongs to the Special Issue Advances in Molecular Mechanisms of Head and Neck Cancers)
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16 pages, 1151 KiB  
Systematic Review
Assessing the Cost-Effectiveness of Photobiomodulation for Oral Mucositis Prevention and Treatment: A Systematic Review
by Susell Parra-Rojas, Juliana Cassol Spanemberg, Nerea del Mar Díaz-Robayna, Mariela Peralta-Mamani and Rocío Trinidad Velázquez Cayón
Biomedicines 2024, 12(10), 2366; https://doi.org/10.3390/biomedicines12102366 - 16 Oct 2024
Cited by 4 | Viewed by 1857
Abstract
Background: We report on the cost-effectiveness of photobiomodulation (PBM) for the prevention and treatment of oral mucositis (OM) derived from the cytotoxic effects of antineoplastic therapy. Methods: This review followed the PRISMA 2020 guidelines. A search was conducted in PubMed, Scopus, Web of [...] Read more.
Background: We report on the cost-effectiveness of photobiomodulation (PBM) for the prevention and treatment of oral mucositis (OM) derived from the cytotoxic effects of antineoplastic therapy. Methods: This review followed the PRISMA 2020 guidelines. A search was conducted in PubMed, Scopus, Web of Science, Embase, and OpenGrey. Articles published before 23 July 2024, were included. Randomized controlled trials (RCTs) that included patients with head and neck cancer undergoing chemotherapy and/or radiotherapy and a placebo group compared to an intervention group (PBM) were selected. The risk of bias was evaluated using the Joanna Briggs Institute tools. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and was rated as moderate. Results: A total of 3 RCTs and 229 patients were included. PBM may represent an additional cost in the short term, but the incremental expenses derived from the cytotoxic effects of antineoplastic therapy are greater in the medium–long term. The intervention group (PBM) showed a lower incidence of severe OM compared to the control group (placebo). Conclusions: PBM is a cost-effective long-term treatment, effective in preventing severe OM and improving the quality of life of cancer patients. More RCTs following the same standardized protocols are needed (registration CDR42024498825). Full article
(This article belongs to the Special Issue Advances in Molecular Mechanisms of Head and Neck Cancers)
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