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Head and Neck Cancers—Novel Approaches and Future Outlook

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

Deadline for manuscript submissions: 31 October 2024 | Viewed by 6764

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Special Issue Editor

Dr. Claudia Maletzki

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Guest Editor

Universitätsmedizin Rostock Zentrum für Innere Medizin, Universität Rostock, Rostock, Germany
Interests: tumor models; immunotherapy; personalized treatment; T cells; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Head and neck squamous cell carcinomas (HNSCCs) are highly heterogeneous. This heterogeneity complicates treatment, and hence, significant advances and improvements in patients’ outcome are needed.

Today, HNSCCs can be stratified according to the human papillomavirus (HPV) infection status, either being negative or positive. Despite the better overall prognosis in case of the latter, many patients present with loco-regionally advanced disease at diagnosis, and this patient cohort has a poor prognosis. The implementation of PD1 targeting antibodies has only moderately improved outcomes. There is increasing evidence of better efficacy in neoadjuvant settings, yet no consensus has been reached to date. This is at least partially attributable to the lack of reliable predictive biomarkers to identify patients with a high likelihood of benefitting from novel treatments. Hence, the implementation of more effective therapies constitutes an unmet need for improving outcomes.

For this Special Issue, we welcome original and review papers that deal with the challenges and recent advances in HNSCC treatment. We especially look for papers that provide insight into new and original research methodologies, better-quality early detection strategies, original treatment approaches, and organization of patients’ care.

Dr. Claudia Maletzki
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. 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

tumor microenvironment
biomarker
patient-derived tumor models
novel treatment approaches
combination strategies
prognostic marker
liquid biopsy
neoadjuvant treatment

Published Papers (6 papers)

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Research

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12 pages, 2957 KiB

Open AccessArticle

Programmed Death Ligand-1 and Tumor Burden Score Dictate Treatment Responses in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

by Ming-Yu Lien, Chih-Chun Wang, Tzer-Zen Hwang, Ching-Yun Hsieh, Chuan-Chien Yang, Chien-Chung Wang, Ching-Feng Lien, Yu-Chen Shih, Shyh-An Yeh and Meng-Che Hsieh

Cancers 2024, 16(9), 1748; https://doi.org/10.3390/cancers16091748 - 30 Apr 2024

Viewed by 273

Abstract

Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan–Meier curves were plotted for outcomes estimation. Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment. Full article

(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)

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18 pages, 1878 KiB

Open AccessArticle

Identifying Predictive Biomarkers for Head and Neck Squamous Cell Carcinoma Response

by Anne-Sophie Becker, Cornelius Kluge, Carsten Schofeld, Annette Helene Zimpfer, Björn Schneider, Daniel Strüder, Caterina Redwanz, Julika Ribbat-Idel, Christian Idel and Claudia Maletzki

Cancers 2023, 15(23), 5597; https://doi.org/10.3390/cancers15235597 - 27 Nov 2023

Cited by 1 | Viewed by 1069

Abstract

The 5-year survival rate for head and neck squamous cell carcinoma (HNSCC) is approximately 65%. In addition to radio-chemotherapy, immunotherapy is an approach in the treatment of advanced HNSCC. A better understanding of the immune context would allow personalized treatment by identifying patients who are best suited for different treatment options. In our discovery cohort, we evaluated the expression profiles of CMTM6, PD-L1, CTLA-4, and FOXP3 in 177 HNSCCs from Caucasian patients of all tumor stages and different treatment regimens, correlating marker expression in tumor and immune cells with outcomes. Patients with CMTM6^high-expressing tumors had a longer overall survival regardless of treatment. This prognostic benefit of CMTM6 in HNSCC was validated in an independent cohort. Focusing on the in the discovery cohort (n = 177), a good predictive effect of CMTM6^high expression was seen in patients receiving radiotherapy (p = 0.07; log rank), but not in others. CMTM6 correlated with PD-L1, CTLA-4 and FOXP3 positivity, with patients possessing CMTM6^high/FOXP3^high tumors showing the longest survival regardless of treatment. In chemotherapy-treated patients, PD-L1 positivity was associated with longer progression-free survival (p < 0.05). In the 27 patients who received immunotherapy, gene expression analysis revealed lower levels of CTLA-4 and FOXP3 with either partial or complete response to this treatment, while no effect was observed for CMTM6 or PD-L1. The combination of these immunomodulatory markers seems to be an interesting prognostic and predictive signature for HNSCC patients with the ability to optimize individualized treatments. Full article

(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)

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12 pages, 1451 KiB

Open AccessArticle

KEAP1/NRF2 Mutations in Stem Cells Define an Aggressive Subset of Head and Neck Cancer Patients Who Have a Poor Prognosis, Lung Metastasis, and Therapeutic Failure

by Syed S. Islam, Bedri Karakas, Abdelilah Aboussekhra and Abu Shadat M. Noman

Cancers 2023, 15(20), 5006; https://doi.org/10.3390/cancers15205006 - 16 Oct 2023

Viewed by 1039

Abstract

Mutations in Keap1/Nrf2 in head and neck cancer result in abnormal cell growth. Progenitor cells, bulk tumor cells, and head and neck cancer stem cells (HN-CSCs) may all harbor these mutations. Nevertheless, whether Keap1/Nrf2 mutations in HN-CSCs have an impact on clinical outcomes is unknown. Cancerous HN-CSCs and benign stem cells were obtained from freshly resected head and neck cancer patients (n = 50) via flow cytometry cell sorting and tested for Keap1/Nrf2 mutations. The existence of Keap1/Nrf2 mutations in HN-CSCs, as well as their correlations with tumor mutations, pathologic tumor stage, tumor histologic grades, lung metastasis, treatment outcomes, and the patient’s age and conditions, are assessed at the last follow-up visit. Thirteen tumors were found to have Keap1/Nrf2 mutations in their HN-CSCs. More than half of the lung metastases and disease progression occurred in HN-CSCs with mutations. Patients whose tumors carried Keap1/Nrf2 mutations in their HN-CSCs had significantly shorter progression-free survival, overall survival, and time of treatment failure than their non-HN-CSC counterparts. These associations were partly driven by HN-CSCs, in which Keap1/Nrf2 mutations were overrepresented in fast progressors and associated with an increased risk of disease progression. Our findings suggest that molecular genotyping of HN-CSCs may facilitate personalized treatment strategies and assist in identifying patients who are likely to benefit from chemotherapy. Full article

(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)

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21 pages, 2884 KiB

Open AccessArticle

Pan-Cancer Analysis of Patient Tumor Single-Cell Transcriptomes Identifies Promising Selective and Safe Chimeric Antigen Receptor Targets in Head and Neck Cancer

by Sanna Madan, Sanju Sinha, Tiangen Chang, J. Silvio Gutkind, Ezra E. W. Cohen, Alejandro A. Schäffer and Eytan Ruppin

Cancers 2023, 15(19), 4885; https://doi.org/10.3390/cancers15194885 - 08 Oct 2023

Viewed by 1388

Abstract

Chimeric antigen receptor (CAR) T cell therapies have yielded transformative clinical successes for patients with blood tumors, but their full potential remains to be unleashed against solid tumors. One challenge is finding selective targets, which we define intuitively to be cell surface proteins that are expressed widely by cancer cells but minimally by healthy cells in the tumor microenvironment and other normal tissues. Analyzing patient tumor single-cell transcriptomics data, we first defined and quantified selectivity and safety scores of existing CAR targets for indications in which they are in clinical trials or approved. We then sought new candidate cell surface CAR targets that have better selectivity and safety scores than those currently being tested. Remarkably, in almost all cancer types, we could not find such better targets, testifying to the near optimality of the current target space. However, in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSC), for which there is currently a dearth of existing CAR targets, we identified a total of twenty candidate novel CAR targets, five of which have both superior selectivity and safety scores. These newly identified cell surface targets lay a basis for future investigations that may lead to better CAR treatments in HNSC. Full article

(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)

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19 pages, 45324 KiB

Open AccessArticle

Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma

by Ke Huang, Xiaoting Gu, Huimei Xu, Hui Li, Mingxuan Shi, Defang Wei, Shiqi Wang, Yao Li, Bin Liu and Yi Li

Cancers 2023, 15(18), 4539; https://doi.org/10.3390/cancers15184539 - 13 Sep 2023

Cited by 3 | Viewed by 922

Abstract

The dual role of necroptosis in inhibiting and promoting tumor development has gradually received much attention because of its essential significance for targeted treatment. Accordingly, this study aims to explore the relationship between necroptosis and oral squamous cell carcinoma (OSCC), and search for novel prognostic factors for OSCC. RNA-seq data and clinical information were downloaded from TCGA and GTEx databases. The prognostic signature of necroptosis-related genes (NRGs) was constructed by univariate Cox regression analysis and the LASSO Cox regression model. Moreover, survival analyses, ROC curves, and nomograms were adopted to further analyze. GO and KEGG analyses and immune infiltration analyses were used for function enrichment and immune feature research in turn. The NRG prognostic signature expression was higher in OSCC tissues than in normal tissues, and the overall survival (OS) rate of the high-expression group was much lower. HPRT1 was proved to be an independent prognostic factor in OSCC. Furthermore, the function enrichment analyses revealed that NRGs were involved in necroptosis, apoptosis, inflammation, and immune reaction. The expression of NRGs was related to immunosuppression in OSCC. Furthermore, the knockdown of HPRT1 could suppress the proliferation and migration of OSCC. In conclusion, the high expression of NRG prognostic signature is associated with poor prognosis in OSCC, and HPRT1 can serve as a novel independent prognostic factor for OSCC. Full article

(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)

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Review

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30 pages, 1765 KiB

Open AccessReview

Immune Escape Strategies in Head and Neck Cancer: Evade, Resist, Inhibit, Recruit

by Kourtney L. Kostecki, Mari Iida, Bridget E. Crossman, Ravi Salgia, Paul M. Harari, Justine Y. Bruce and Deric L. Wheeler

Cancers 2024, 16(2), 312; https://doi.org/10.3390/cancers16020312 - 11 Jan 2024

Viewed by 1444

Abstract

Head and neck cancers (HNCs) arise from the mucosal lining of the aerodigestive tract and are often associated with alcohol use, tobacco use, and/or human papillomavirus (HPV) infection. Over 600,000 new cases of HNC are diagnosed each year, making it the sixth most common cancer worldwide. Historically, treatments have included surgery, radiation, and chemotherapy, and while these treatments are still the backbone of current therapy, several immunotherapies have recently been approved by the Food and Drug Administration (FDA) for use in HNC. The role of the immune system in tumorigenesis and cancer progression has been explored since the early 20th century, eventually coalescing into the current three-phase model of cancer immunoediting. During each of the three phases—elimination, equilibrium, and escape—cancer cells develop and utilize multiple strategies to either reach or remain in the final phase, escape, at which point the tumor is able to grow and metastasize with little to no detrimental interference from the immune system. In this review, we summarize the many strategies used by HNC to escape the immune system, which include ways to evade immune detection, resist immune cell attacks, inhibit immune cell functions, and recruit pro-tumor immune cells. Full article

(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)

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