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The Genetics of Head and Neck Squamous Cell Carcinoma
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The Genetics of Head and Neck Squamous Cell Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 1378

Special Issue Editor

Dr. Sabrina Daniela da Silva

E-Mail Website
Guest Editor
Department of Otolaryngology—Head and Neck Surgery, McGill University, Montreal, QC H3T 1E2, Canada
Interests: carcinogenesis; cancer progression; metastasis signaling; preclinical and animal models; genetic; genomic and epigenomic; target and drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck squamous cell carcinoma (HNSCC) remains a significant global health burden, with complex genetic and molecular underpinnings that continue to shape diagnostic, prognostic, and therapeutic strategies. Recent advances in genomic technologies have uncovered a vast array of genetic mutations, epigenetic alterations, and molecular pathways driving HNSCC initiation and progression. Understanding these genetic underpinnings is crucial for developing novel therapeutic strategies, improving patient stratification, and enhancing clinical outcomes. This Special Issue aims to explore the latest advancements in understanding the genetic landscape of HNSCC, highlighting innovations in genomic profiling, biomarker discovery, and precision oncology approaches. We seek to create a comprehensive collection of research that advances knowledge on the interplay between genetic alterations, tumor biology, and the tumor microenvironment, ultimately driving more effective, individualized treatment options. This Special Issue aligns with the journal’s commitment to advancing cancer research and precision medicine, ensuring a balance of foundational insights and translational applications.

We welcome submissions of original research articles, reviews, and short communications addressing key genetic insights into HNSCC development, progression, and treatment resistance. Topics may include, but are not limited to, the following:

  • Genomic and transcriptomic profiling of HNSCC subtypes;
  • Somatic mutations and their clinical significance;
  • Epigenetic regulation and chromatin remodeling in HNSCC;
  • Biomarker discovery for diagnosis, prognosis, and therapy response;
  • Genetic drivers of treatment resistance;
  • The role of the tumor microenvironment in genetic alterations;
  • Precision medicine approaches targeting genetic vulnerabilities;
  • Comparative genetics between HPV-positive and HPV-negative HNSCC;
  • Liquid biopsy and circulating tumor DNA for genetic monitoring.

We look forward to your valuable contributions and collaboration in advancing this vital area of oncology research.

Best,

Dr. Sabrina Daniela da Silva
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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 squamous cell carcinoma
  • tumor genetics
  • genomic profiling
  • precision oncology
  • biomarkers
  • tumor microenvironment
  • epigenetics
  • somatic mutations
  • molecular pathways
  • targeted therapies

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Published Papers (2 papers)

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Research

16 pages, 5919 KB  
Article
p53 Positivity Predicts Poor Survival in Oropharyngeal Squamous Cell Carcinoma Dependent on HPV Status
by Lilianny Querino Rocha de Oliveira, Fatemeh Farshadi, Alex Mlynarek, Marco A. Mascarella, Michael Hier, Ricardo D. Coletta and Sabrina Daniela Silva Wurzba
Cancers 2026, 18(10), 1660; https://doi.org/10.3390/cancers18101660 - 20 May 2026
Viewed by 375
Abstract
Background: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) generally has a more favorable prognosis compared to HPV-negative cases. Overexpression of p16INK4a is widely used as a surrogate marker for HPV-induced carcinogenesis, and it also represents an important tumor suppressor gene, the [...] Read more.
Background: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) generally has a more favorable prognosis compared to HPV-negative cases. Overexpression of p16INK4a is widely used as a surrogate marker for HPV-induced carcinogenesis, and it also represents an important tumor suppressor gene, the second most frequently altered after TP53. In turn, mutations in TP53 are characteristic of tumors linked to smoking and alcohol consumption and p53 expression is consistently associated with worse clinical outcomes. Aims: Investigate the impact of p53 immunohistochemical expression on prognosis of OPSCC. Methods: This retrospective study included 155 OPSCC patients with longitudinal follow-up exceeding 10 years. Immunohistochemistry was used to evaluate p53 protein expression. Clinicopathological associations were performed to evaluate the prognostic impact of p53 protein expression in OPSCC HPV-positive and HPV-negative tumors. Results: Among the 155 OPSCC cases, 90 (58.1%) were classified as HPV-positive and 65 (41.9%) as HPV-negative. HPV status was inversely associated with p53 positivity, with HPV-negative tumors showing a higher frequency of p53 expression (p < 0.0001). Patients with HPV-positive tumors experienced better clinical outcomes than those with HPV-negative disease, including cancer-specific survival (CSS; HR: 3.47, 95% CI 1.16–10.4, p = 0.02) and disease-free survival (DFS; HR: 3.73, 95% CI 1.29–10.7, p = 0.01), whereas p53 positivity alone was not independently associated with survival. Notably, individuals with HPV-negative and p53-positive tumors exhibited the poorest outcomes, in contrast to patients with HPV-positive OPSCC, regardless of p53 expression. Conclusions: Patients with HPV-negative and p53-positive OPSCC showed inferior clinical outcomes compared with their HPV-positive counterparts, independent of p53 status. These findings underscore the prognostic relevance of jointly evaluating HPV status and p53 expression in OPSCC and support more refined risk stratification and personalized therapeutic strategies. Full article
(This article belongs to the Special Issue The Genetics of Head and Neck Squamous Cell Carcinoma)
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14 pages, 2875 KB  
Article
Tumor-Specific Pro-Thrombotic Gene Expression in Head and Neck Squamous Cell Carcinoma: A Multi-Cohort Transcriptomic Analysis
by Kiranya E. Arnold, Nadia Debick, John Brognard and Auyon J. Ghosh
Cancers 2026, 18(7), 1055; https://doi.org/10.3390/cancers18071055 - 25 Mar 2026
Viewed by 639
Abstract
Objectives: Head and neck tumors have been associated with varying risks for venous thromboembolism (VTE). Through a cross-tumor comparison, we assessed site-specific coagulation-related gene expression changes in head and neck squamous cell carcinoma (HNSCC) compared to squamous cell tumors in the esophagus [...] Read more.
Objectives: Head and neck tumors have been associated with varying risks for venous thromboembolism (VTE). Through a cross-tumor comparison, we assessed site-specific coagulation-related gene expression changes in head and neck squamous cell carcinoma (HNSCC) compared to squamous cell tumors in the esophagus (ESCCa) and lung (LUSC). Further, we assessed the relationship between clinicopathologic features of HNSCC and coagulome gene expression. Methods: RNA-sequencing data from primary tumor tissues of HNSCCa, ESCCa, and LUSC were obtained from The Cancer Genome Atlas (TCGA). Three previously identified pro-thrombotic genes (F3, SERPINE1, and SERPINB2) were analyzed and, for pan-cancer comparisons, gene expression was Z-standardized and summarized as a composite coagulome score. For HNSCCa-specific analyses, gene expression was compared using log2 RSEM counts, contrasting between HPV status, primary tumor site, tumor stage, grade, and demographic characteristics. Results: HNSCCa demonstrated the highest composite coagulome activation (mean Z-score = 0.29, 95% CI: 0.23–0.35) compared with LUSC and ESCCa (mean Z-scores = −0.27 and −0.16, respectively; p < 0.001). Among 487 HNSCCa tumors, HPV-negative tumors exhibited significantly higher composite coagulome expression than HPV-positive tumors (mean ± SD, 11.25 ± 1.39 vs. 10.14 ± 1.30; p < 0.001). Oral cavity tumors demonstrated the highest coagulome expression, while oropharyngeal tumors were most suppressed. Higher histologic grade was inversely associated with coagulome expression (p < 0.001). Patient age, sex, and race were not significantly associated with coagulome expression. Conclusions: HNSCCa exhibits a tumor-specific pro-thrombotic expression profile with substantial heterogeneity driven by HPV status and primary tumor site. Despite elevated tumor-specific pro-coagulant signaling, these findings reflect tumor-specific pro-thrombotic potential rather than clinical VTE risk in HNSCCa, which likely remains context-dependent and may require additional inflammatory or treatment-related triggers to clinically manifest. Full article
(This article belongs to the Special Issue The Genetics of Head and Neck Squamous Cell Carcinoma)
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