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Biomedicines
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Head and Neck Tumors, 4th Edition
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Head and Neck Tumors, 4th Edition

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

Deadline for manuscript submissions: 31 October 2025 | Viewed by 4734

Special Issue Editors

Dr. Silvia Di Agostino

E-Mail Website
Guest Editor
Oncogenomic and Epigenetic Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Regina Elena National Cancer Institute, 00144 Rome, Italy
Interests: genomic instability; cell cycle checkpoints; dna repair; transcriptional regulation; molecular oncology; head and neck; p53 family; mutant p53; hippo pathway
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jan B. Vermorken

E-Mail Website
Guest Editor
1. Center for Oncological Research Antwerp, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
2. Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium
Interests: cancer biology; cancer therapy; oncology; toxicity; pharmacodynamics; chemotherapy; treatment; cancer; tumors; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck cancers dramatically impact patients' quality of life. Recently, remarkable progress has been made in reconstructive medical devices, and the use of stem cells has improved prosthetic support. However, there is still a need to improve early diagnosis and screening methodologies.

This new Special Issue aims to present original, translational molecular, or clinical research and review articles that focus on the different aspects of head and neck pathology, including the following: identification of molecular markers of diagnosis, prognosis, and efficacy of therapy (e.g., liquid biopsy); new hypotheses of precision treatment; and the use of nanotechnologies and biomaterials to improve clinical outcome of the patients. Much interest will be devoted to the translational molecular mechanisms of recurrence and metastasis processes.

Dr. Silvia Di Agostino
Prof. Dr. Jan B. Vermorken
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • head and neck tumors
  • predictive markers
  • liquid biopsy
  • therapy
  • precision medicine
  • biomaterials

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Published Papers (6 papers)

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Research

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12 pages, 1280 KiB  
Article
Structured Early Follow-Up in Head and Neck Squamous Cell Carcinomas: A Retrospective Cohort Study
by Philipp Dittmann, Bernhard Lehnert, Friedrich Ihler, Chia-Jung Busch and Markus Blaurock
Biomedicines 2025, 13(5), 1246; https://doi.org/10.3390/biomedicines13051246 - 20 May 2025
Viewed by 786
Abstract
Background/Objectives: The various head and neck squamous cell carcinoma (HNSCC) subtypes are among the most common cancers globally, with significant recurrence rates within the first two years post-treatment. Despite advancements in treatment, structured early follow-up remains crucial for timely diagnosis and effective salvage [...] Read more.
Background/Objectives: The various head and neck squamous cell carcinoma (HNSCC) subtypes are among the most common cancers globally, with significant recurrence rates within the first two years post-treatment. Despite advancements in treatment, structured early follow-up remains crucial for timely diagnosis and effective salvage treatment. Methods: This retrospective study examines the impact of implementing a structured initial restaging between three and six months after the conclusion of initial treatment. The study population included 532 patients treated with curative intent at the University Medicine of Greifswald, Germany, between 2010 and 2019. Patients were divided into two groups: standard follow-up (SF) and adapted follow-up (AF). The AF group received standardized post-treatment restaging, including imaging and panendoscopy or PET-CT exams. Results: We found a trend towards earlier diagnosis and a reduction in recurrences, although these differences were not statistically significant. Secondary cancers were observed more frequently in the AF group, significantly affecting overall survival. Conclusions: Our cohort supports structured initial cancer follow-up in HNSCC. Although not significant, an initial multimodal exam after treatment was well tolerated and showed a trend toward earlier diagnosis. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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18 pages, 2924 KiB  
Article
The Potential Role of SP-G and PLUNC in Tumor Pathogenesis and Wound Healing in the Human Larynx
by Aurelius Scheer, Lars Bräuer, Markus Eckstein, Heinrich Iro, Friedrich Paulsen, Fabian Garreis, Martin Schicht and Antoniu-Oreste Gostian
Biomedicines 2025, 13(5), 1240; https://doi.org/10.3390/biomedicines13051240 - 20 May 2025
Viewed by 604
Abstract
Background: Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two [...] Read more.
Background: Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two surfactant family proteins SP-G and PLUNC in healthy glottis, the presence of SP-G in glottic cancer, and the in vitro tissue regeneration potential of SP-G and PLUNC on epithelial cells. Methods: The expression and distribution of SP-G and PLUNC were investigated immunohistochemically in squamous cell carcinomas of the vocal folds. The expression of both proteins was analyzed by Western blot in micro-dissected healthy vocal fold mucosa from body donors. The hypopharyngeal squamous carcinoma cell line (FaDu) was used as an in vitro model for wound healing experiments with Electric cell–substrate impedance sensing (ECIS). Results: The results show the presence of SP-G and PLUNC in epithelial cells of the healthy vocal folds and the submucosal glands of the vestibular folds. SP-G was detected in squamous cell carcinomas of the vocal folds. SP-G and PLUNC show accelerated wound healing of FaDu cells in vitro. Conclusions: SP-G and PLUNC were first detected in the vocal fold of the human larynx. SP-G shows a distinct presence in glottic carcinoma, whose relevance needs to be determined in future studies. SP-G and PLUNC exhibit a positive influence on the repair mechanisms of epithelial lesions of the glottis. The data presented form the basis for follow-up studies focusing on the impact of SP-G in glottic cancer development and the potentially meaningful clinical effect of SP-G and PLUNC on tissue repair of the human vocal fold. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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14 pages, 4134 KiB  
Article
Patient-Derived Cancer-Associated Fibroblasts Support the Colonization of Tumor Cells in Head and Neck Squamous Cell Carcinoma
by Julia Federspiel, Teresa Bernadette Steinbichler, Samuel Moritz Vorbach, Marie Theres Eling, Wegene Borena, Christof Seifarth, Benedikt Gabriel Hofauer and Jozsef Dudas
Biomedicines 2025, 13(2), 358; https://doi.org/10.3390/biomedicines13020358 - 4 Feb 2025
Cited by 1 | Viewed by 1527
Abstract
Background: The crosstalk between cancer-associated fibroblasts (CAFs) and tumor cells promotes proliferation, tumor relapse, and the acquisition of a partial epithelial-to-mesenchymal (pEMT) phenotype in tumor cells. The aim of this study was to investigate the effects of patient-derived CAFs on tumor cell growth [...] Read more.
Background: The crosstalk between cancer-associated fibroblasts (CAFs) and tumor cells promotes proliferation, tumor relapse, and the acquisition of a partial epithelial-to-mesenchymal (pEMT) phenotype in tumor cells. The aim of this study was to investigate the effects of patient-derived CAFs on tumor cell growth and radioresistance in head and neck squamous cell carcinoma (HNSCC). Methods: CAFs were isolated and cultured in a three-dimensional spheroid formation. SCC-25 tumor cells educated by the CAFs (SCC25-E cells) were subjected to irradiation, and the response of the CAF-stimulated tumor cells to radiotherapy was determined using an MTT assay, a clonogenic assay, and Western blotting. Tumor cell morphological changes and growth dynamics were assessed using 3D holotomographic microscopy and a live video microscope. Results: Patient-derived CAFs significantly increased the growth rate of SCC-25 cells. CAFs drove fibrosis in the tumor microenvironment (TME), functioned as a physical barrier, temporarily stopped tumor growth, and induced the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Viability after irradiation at 4–8 Gy was significantly higher in SCC25-E cells than in the controls (p = 8 × 10–4 or lower). Furthermore, irradiation triggered the pEMT profile in HNSCC cells. Conclusions: CAFs’ education of tumor cells and the induced p38 phosphorylation had no influence on irradiation sensitivity. SCC25-E cultures demonstrated increased tumor cell growth, viability, and stress-induced phospho-p38 activation. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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Review

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25 pages, 3910 KiB  
Review
Novel Therapeutic Strategies for Squamous Cell Carcinoma of the Head and Neck: Beyond EGFR and Checkpoint Blockade
by Rachel Hui Zhen Sim, Pei Jye Voon, Seng Wee Cheo and Darren Wan-Teck Lim
Biomedicines 2025, 13(8), 1972; https://doi.org/10.3390/biomedicines13081972 - 14 Aug 2025
Abstract
Despite advances in immunotherapy with checkpoint inhibitors, a significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) do not respond to treatment or eventually develop resistance. This review focuses on novel therapeutic strategies currently under investigation for HNSCC, moving beyond [...] Read more.
Despite advances in immunotherapy with checkpoint inhibitors, a significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) do not respond to treatment or eventually develop resistance. This review focuses on novel therapeutic strategies currently under investigation for HNSCC, moving beyond the established paradigms of EGFR inhibition and PD-1/PD-L1 blockade. We explore emerging targets and drug classes, including next-generation immunotherapies, targeted therapies directed at specific molecular alterations, epigenetic modifiers, agents targeting the tumor microenvironment, and innovative approaches like cell-based therapies and oncolytic viruses. We discuss the preclinical rationale and clinical data (where available) for these novel approaches, highlighting the challenges and opportunities in translating these discoveries into improved outcomes for patients with HNSCC. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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25 pages, 1677 KiB  
Review
The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy
by Daria Maria Filippini, Donatella Romaniello, Francesca Carosi, Laura Fabbri, Andrea Carlini, Raffaele Giusti, Massimo Di Maio, Salvatore Alfieri, Mattia Lauriola, Maria Abbondanza Pantaleo, Lorena Arribas, Marc Oliva, Paolo Bossi and Laura Deborah Locati
Biomedicines 2025, 13(8), 1931; https://doi.org/10.3390/biomedicines13081931 - 8 Aug 2025
Viewed by 479
Abstract
Background: Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head [...] Read more.
Background: Growth Differentiation Factor 15 (GDF15) has emerged as a key biomarker and therapeutic target in oncology, with roles extending beyond cancer cachexia. Elevated GDF15 levels correlate with poor prognosis across several solid tumors, including colorectal, gastric, pancreatic, breast, lung, prostate, and head and neck cancers. GDF15 modulates tumor progression through PI3K/AKT, MAPK/ERK, and SMAD2/3 signaling, thereby promoting epithelial-to-mesenchymal transition, metastasis, immune evasion, and chemoresistance via Nrf2 stabilization and oxidative stress regulation. Methods: We performed a narrative review of the literature focusing on the role of GDF15 in solid tumors, with a particular emphasis on head and neck cancers. Results: In head and neck squamous cell carcinoma (HNSCC), GDF15 overexpression is linked to aggressive phenotypes, radioresistance, poor response to induction chemotherapy, and failure of immune checkpoint inhibitors (ICIs). Similar associations are observed in colorectal, pancreatic, and prostate cancer, where GDF15 contributes to metastasis and therapy resistance. Targeting the GDF15-GFRAL axis appears therapeutically promising: the monoclonal antibody ponsegromab improved cachexia-related outcomes in the PROACC-1 trial, while visugromab combined with nivolumab enhanced immune response in ICI-refractory tumors. Conclusions: Further investigation is warranted to delineate the role of GDF15 across malignancies, refine patient selection, and evaluate combinatorial approaches with existing treatments. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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14 pages, 624 KiB  
Review
Merkel Cell Polyomavirus (MCPyV) and Its Possible Role in Head and Neck Cancers
by Sara Passerini, Sara Messina, Ugo Moens and Valeria Pietropaolo
Biomedicines 2025, 13(5), 1180; https://doi.org/10.3390/biomedicines13051180 - 12 May 2025
Cited by 1 | Viewed by 770
Abstract
Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with [...] Read more.
Despite significant progress in its prevention, diagnosis, and treatment, head and neck cancer (HNC) remains a major global health issue due to its multifactorial pathogenesis. Indeed, HNCs have been found to be associated with different environmental and lifestyle factors, as well as with infection with oncogenic viruses. To date, seven viruses are recognized for their tumorigenic properties and have been proposed as implicated in HNC development, including Merkel Cell Polyomavirus (MCPyV). MCPyV is well recognized as the major etiological agent of Merkel cell carcinoma (MCC), a rare but rapidly metastasizing skin neoplasm. Specifically, in almost 80% of MCC cases, viral genome integration occurs, and a truncated form of Large T Antigen (tLT) is expressed. Although MCC is a rare cancer, MCPyV is a ubiquitous virus, widely distributed among the human population. Therefore, a plausible role of the virus has been proposed, even for other tumors. The current review provides an overview of the available data describing the presence of MCPyV in non-MCC tumors, such as HNCs, with the aim of elucidating the potential contribution of MCPyV to oral cancer. Understanding the role of viral infections in the etiology of cancer opens up the opportunity for developing preventive measures and targeted therapies that effectively address HNC progression while reducing treatment-related side effects. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)
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