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Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 13337

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Special Issue Editor

Prof. Dr. Lorenzo Lo Muzio

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Guest Editor

Direttore della Sezione di Medicina Sperimentale del Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Foggia, Italy
Interests: oral cancer; cancer stem cell; biomarkers; protein function; protein bioinformatics; protein–protein interactions; structure bioinformatics; cancer pharmaco-omics modelling; biomarker discovery; precision oncology; chemoinformatics; drug discovery informatics; virtual screening
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The incidence rate of head and neck tumors has increased rapidly in recent years, especially among young adults. New risk factors seem to be involved in their pathogenesis, particularly in young people, such as papillomaviruses. Human papillomavirus (HPV) infection is involved in a growing percentage of subsets of head and neck tumors, such as oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, and laryngeal squamous cell carcinoma. However, head and neck tumors are very heterogeneous, comprising several subtypes in different anatomic sites of the upper aerodigestive tracts (the nasal cavity, oral cavity, oropharynx, pharynx, hypopharynx, and larynx), with complex pathologic and molecular features. Despite advances in medical imaging and therapeutic approaches, the outcome of patients with advanced head and neck cancer remains poor, and the five‐year survival is still at <50%. Targeted therapy is a promising tool in the context of immunotherapy and/or epigenetic therapy. The use of genetic and epigenetic biomarkers should be introduced in disease detection, as well as disease and treatment monitoring.

Leading by Prof. Lorenzo Lo Muzio and assisting by our Topical Advisory Panel Member Dr. Francesca Spirito (University of Foggia), this Special Issue aims to expand the current molecular knowledge around head and neck tumors useful for the diagnosis, prognosis, and therapy of these tumors. Suitable topics include HNC genomics, epigenomics, transcriptomics, proteomics, and metabolomics, as well as diagnosis, epidemiology, pathology, immunology, therapy, and monitoring. We encourage experts to discuss their experiences and results involving experimental studies using in vitro and in vivo models, including patient-derived xenograft animal models, biomarker analyses of patient saliva or other body fluids, and tumor-derived microRNA or extracellular vesicles, as well as review articles, noting the Special Issue focus on molecular research, which means that pure clinical research will not be accepted.

Prof. Dr. Lorenzo Lo Muzio
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
diagnosis
prognosis
therapeutic opportunities
oral cancer
non-coding RNAs (ncRNAs)
miRNAs
lncRNAs
chemo/radioresistance
metastasis

Published Papers (6 papers)

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Research

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12 pages, 2495 KiB

Open AccessArticle

Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading

by Irene Montoro-Jiménez, Rocío Granda-Díaz, Sofía T. Menéndez, Llara Prieto-Fernández, María Otero-Rosales, Miguel Álvarez-González, Vanessa García-de-la-Fuente, Aida Rodríguez, Juan P. Rodrigo, Saúl Álvarez-Teijeiro, Juana M. García-Pedrero and Francisco Hermida-Prado

Int. J. Mol. Sci. 2024, 25(5), 2695; https://doi.org/10.3390/ijms25052695 - 26 Feb 2024

Viewed by 695

Abstract

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading. Full article

(This article belongs to the Special Issue Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities)

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Graphical abstract

15 pages, 1411 KiB

Open AccessArticle

Data Normalization of Urine miRNA Profiling from Head and Neck Cancer Patients Treated with Cisplatin

by Nadine de Godoy Torso, Julia Coelho França Quintanilha, Maria Aparecida Cursino, Eder de Carvalho Pincinato, Carmen Silvia Passos Lima and Patricia Moriel

Int. J. Mol. Sci. 2023, 24(13), 10884; https://doi.org/10.3390/ijms241310884 - 29 Jun 2023

Cited by 1 | Viewed by 1177

Abstract

The microRNA (miRNA) expression profile by qRT-PCR depends directly on the most appropriate normalization strategy adopted; however, currently there is no universally adequate reference gene. Therefore, this study aimed to determine, considering RNA-Seq results, the most adequate endogenous normalizer for use in the relative quantification of urine miRNAs from head and neck cancer patients, treated with cisplatin chemoradiotherapy. The massive sequencing was performed to identify the miRNAs differentially expressed between the group with cisplatin nephrotoxicity (n = 6) and the one without (n = 6). The candidate endogen normalizer was chosen according to four criteria: (1) the miRNA must be expressed in most samples; (2) the miRNA must have a fold change value between 0.99 and 1.01; (3) the miRNA must have a p-value ≥ 0.98; and (4) the miRNA must not be commented on by the final GeneGlobe (Qiagen, Hilden, Germany) analysis. Four miRNAs met all the criteria (hsa-miR-363-5p, hsa-miR-875-5p, hsa-miR-4302, and hsa-miR-6749-5p) and were selected for validation by qRT-PCR in a cohort of 49 patients (including the 12 sequencing participants). Only hsa-miR-875-5p was shown to be an adequate normalizer for the experimental condition under investigation, as it exhibited invariant expression between the two groups. Full article

(This article belongs to the Special Issue Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities)

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14 pages, 2466 KiB

Open AccessArticle

TRIM21 Expression as a Prognostic Biomarker for Progression-Free Survival in HNSCC

by Amelie von Bernuth, Julika Ribbat-Idel, Luise Klapper, Tobias Jagomast, Dirk Rades, Anke Leichtle, Ralph Pries, Karl-Ludwig Bruchhage, Sven Perner, Anne Offermann, Verena Sailer and Christian Idel

Int. J. Mol. Sci. 2023, 24(6), 5140; https://doi.org/10.3390/ijms24065140 - 07 Mar 2023

Cited by 4 | Viewed by 1529

Abstract

Patients with head and neck squamous cell carcinoma (HNSCC) continue to have a rather poor prognosis. Treatment-related comorbidities have negative impacts on their quality of life. TRIM21 is a cytosolic E3 ubiquitin ligase that was initially described as an autoantigen in autoimmune diseases and later associated with the intracellular antiviral response. Here, we investigated the role of TRIM21 as a biomarker candidate for HNSCC in predicting tumor progression and patient survival. We analyzed TRIM21 expression and its association with clinical-pathological parameters in our HNSCC cohort using immunohistochemistry. Our HNSCC cohort included samples from 419 patients consisting of primary tumors (n = 337), lymph node metastases (n = 156), recurrent tumors (n = 54) and distant metastases (n = 16). We found that cytoplasmic TRIM21 expression was associated with the infiltration of immune cells into primary tumors. In addition, TRIM21 expression was significantly higher in primary tumors than in lymph node metastases, and increased TRIM21 expression was correlated with shorter progression-free survival in HNSCC patients. These results suggest that TRIM21 could be a new biomarker for progression-free survival. Full article

(This article belongs to the Special Issue Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities)

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Review

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24 pages, 1747 KiB

Open AccessReview

Human Papilloma Virus Positive Oropharyngeal Squamous Cell Carcinoma and the Immune System: Pathogenesis, Immunotherapy and Future Perspectives

by A. Khoo, M. Boyer, Z. Jafri, T. Makeham, T. Pham, L. M. Khachigian, P. Floros, E. Dowling, K. Fedder, D. Shonka, Jr., J. Garneau and C. H. O’Meara

Int. J. Mol. Sci. 2024, 25(5), 2798; https://doi.org/10.3390/ijms25052798 - 28 Feb 2024

Viewed by 1186

Abstract

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV⁺OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV⁺OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV⁺OPSCC. Full article

(This article belongs to the Special Issue Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities)

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15 pages, 1059 KiB

Open AccessReview

The Role of Deubiquitinating Enzyme in Head and Neck Squamous Cell Carcinoma

by Shengjian Jin, Yasusei Kudo and Taigo Horiguchi

Int. J. Mol. Sci. 2023, 24(1), 552; https://doi.org/10.3390/ijms24010552 - 29 Dec 2022

Cited by 5 | Viewed by 1970

Abstract

Ubiquitination and deubiquitination are two popular ways for the post-translational modification of proteins. These two modifications affect intracellular localization, stability, and function of target proteins. The process of deubiquitination is involved in histone modification, cell cycle regulation, cell differentiation, apoptosis, endocytosis, autophagy, and DNA repair after damage. Moreover, it is involved in the processes of carcinogenesis and cancer development. In this review, we discuss these issues in understanding deubiquitinating enzyme (DUB) function in head and neck squamous cell carcinoma (HNSCC), and their potential therapeutic strategies for HNSCC patients are also discussed. Full article

(This article belongs to the Special Issue Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities)

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Figure 1

16 pages, 3070 KiB

Open AccessReview

Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis

by Fábio França Vieira e Silva, María Elena Padín-Iruegas, Vito Carlo Alberto Caponio, Alejandro I. Lorenzo-Pouso, Paula Saavedra-Nieves, Cintia Micaela Chamorro-Petronacci, José Suaréz-Peñaranda and Mario Pérez-Sayáns

Int. J. Mol. Sci. 2022, 23(19), 11937; https://doi.org/10.3390/ijms231911937 - 08 Oct 2022

Cited by 27 | Viewed by 5889

Abstract

Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management, prognosis and effectiveness of treatments. Proteins related to apoptotic machinery have been identified as potential biomarkers. Caspase 3 is the main effector caspase and has a key role in apoptosis. The objective of this systematic review and meta-analysis is to review studies that analyze changes in Caspase 3 and Cleaved Caspase 3 expression both in oral premalignant disorders (OPMD) as well as in head and neck cancer (HNC). This study also proposes to review the prognostic values associated with HNC according to the expression of Caspase 3. Medline (via PubMed), EMBASE, Scopus, Cochrane, Web of Science and Grey Literature Database were screened from inception to june of 2022 and 18 studies were selected and 8 were included in the prognostic meta-analysis. Results related to the comparison of Caspase 3 expression demonstrated similar expression of Caspase 3 in HNC, with an average of 51.9% (9.5–98.1) showing high/moderate expression compared to 45.7% (14.6–84.7) in OPMD. Of interest, Cleaved Caspase 3 resulted incresed in HNC when compared with OPMD, being 73.3% (38.6–88.3) versus 22.9% (7.1–38.7). Pooled Fixed effect of HR values (95% CI) for OS related to Caspase 3 IHC expression in HNC patients was 1.48 (95% CI 0.95–2.28); also, the rate of heterogeneity was low, as revealed by I² = 31%. For DFS was 1.07 (95% CI 0.79–1.45) with I² = 0% and DSS showed a HR of 0.88 (95% CI 0.69–1.12) with I² = 37%. Caspase 3 and Cleaved Caspase 3 expression could be linked with malignancy progression, but the expression of Caspase 3 did not influence the prognosis of patients with HNC. Full article

(This article belongs to the Special Issue Head and Neck Tumors: New Diagnostic, Prognostic and Therapeutic Opportunities)

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