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2nd Edition: Targeting Head and Neck Cancer

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

Deadline for manuscript submissions: closed (20 September 2023) | Viewed by 24494

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Special Issue Editors

Prof. Dr. Michiel Wilhelmus Maria Van den Brekel

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Guest Editor

Department of Head and Neck Surgery ,The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Interests: head and neck cancer; molecular biology; imaging; rehabilitation
Special Issues, Collections and Topics in MDPI journals

Dr. Bhuvanesh Singh

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Guest Editor

Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Interests: head and neck cancer; molecular biology; translational medicine
Special Issues, Collections and Topics in MDPI journals

Dr. Charlotte Zuur

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Guest Editor

Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Interests: head and neck cancer; translational research; novel treatments
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the Special Issue "Targeting Head and Neck Cancer" (https://www.mdpi.com/journal/cancers/special_issues/head_neck).

Targeted therapies for head and neck cancer are crucial to personalizing treatment and improving outcomes. Genetic profiling of tumors has revealed several subtypes, but currently only HPV-associated tumors are seen as distinct entities. Additionally, subtypes with more DNA repair deficits, hypoxia, EMT, and other pathway aberrations have been identified. Unfortunately, this has not yet led to novel treatment protocols. Chemotherapy and small molecules have so far not played an important role in the curative setting in head and neck cancer. However, in the palliative setting, especially in salivary gland cancer, more targeted therapies are becoming available, and in several basket trials, genetic profiling is used to select the most optimal strategy. In the neoadjuvant setting, chemotherapy, targeted molecules, and immunotherapy are being explored. So far only cisplatin and cetuximab are widely utilized as radiosensitizers, but no reliable biomarkers are used to predict a response. PARP inhibition has been shown to act as a strong radiosensitizer and is currently under investigation. One major issue is the lack of reliable biomarkers and in vitro systems able to predict a response. This Special Issue covers several aspects of targeted treatment. Researchers studying biomarkers, as well as model systems and trials using a targeted approach, are invited to submit manuscripts.

Prof. Dr. Michiel Wilhelmus Maria Van den Brekel
Dr. Bhuvanesh Singh
Dr. Charlotte Zuur
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 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

targeted therapy
biomarkers
head and neck cancer
model systems
radiosensitizer
immunotherapy
pathway inhibition
salivary gland carcinoma
personalized medicine

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Published Papers (13 papers)

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15 pages, 963 KiB

Open AccessArticle

Building a Bridge to Community: A Pragmatic Randomized Trial Examining a Combined Physical Therapy and Resistance Exercise Intervention for People after Head and Neck Cancer

by Margaret L. McNeely, K. Ming Chan, Ryan A. Spychka, Joni Nedeljak, Brock Debenham, Naresh Jha and Hadi Seikaly

Cancers 2024, 16(9), 1758; https://doi.org/10.3390/cancers16091758 - 1 May 2024

Viewed by 1205

Abstract

Background: Established barriers to general exercise and physical activity among individuals with head and neck cancer include dry mouth, difficulty eating, weight loss, fear of injury, comorbidities, and treatment-related symptoms of pain and fatigue. Methods/Design: A 12-week pragmatic randomized controlled trial was conducted followed by an optional supported exercise transition phase. Eligible participants were individuals with head and neck cancers who had undergone surgery and/or radiation therapy to lymph node regions in the neck. Participants were randomized to a comparison group involving a shoulder and neck physiotherapeutic exercise protocol, or to a combined experimental group comprising the shoulder and neck physiotherapeutic exercise protocol and lower-body resistance exercise training. The primary outcome of this study was fatigue-related quality of life. Results: Sixty-one participants enrolled, 59 (97%) completed the randomized trial phase, 55 (90%) completed the 24-week follow-up, and 52 (85%) completed the one-year follow-up. Statistically significant between-group differences were found in favor of the combined experimental group for the fatigue-related quality of life, fitness outcomes, and overall physical activity. Paired comparisons confirmed significant within-group improvements for both groups from baseline to one-year follow-up across most outcomes. Discussion: A group-based combined physiotherapeutic and lower-body resistance exercise program was feasible and effective. Findings are limited to individuals who had undergone a surgical neck dissection procedure. Given the complexity of head and neck cancer, further pragmatic interdisciplinary research is warranted. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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18 pages, 504 KiB

Open AccessArticle

Multi-Domain Screening: Identification of Patient’s Risk Profile Prior to Head-and-Neck Cancer Treatment

by Monse W. M. Wieland, Walmari Pilz, Bjorn Winkens, Ann Hoeben, Anna C. H. Willemsen, Bernd Kremer and Laura W. J. Baijens

Cancers 2023, 15(21), 5254; https://doi.org/10.3390/cancers15215254 - 1 Nov 2023

Cited by 1 | Viewed by 1780

Abstract

Background: Head-and-neck cancer (HNC) can give rise to oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty. Early identification of these phenomena in newly diagnosed HNC patients is important to reduce the risk of complications and to improve treatment outcomes. The aim of this study was (1) to determine the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty; and (2) to investigate the relation between these phenomena and patients’ age, performance status, and cancer group staging. Methods: Patients (N = 128) underwent multi-domain screening consisting of the Eating Assessment Tool-10 for OD, Short Nutritional Assessment Questionnaire and BMI for malnutrition, Short Physical Performance Battery and Hand Grip Strength for sarcopenia, and Distress Thermometer and Maastricht Frailty Screening Tool for frailty. Results: 26.2%, 31.0%, 73.0%, and 46.4% of the patients were at risk for OD, malnutrition, sarcopenia, or frailty, respectively. Patients with an advanced cancer stage had a significantly higher risk of OD and high levels of distress prior to cancer treatment. Conclusions: This study identified the risk profile of newly diagnosed HNC patients using a standardized ‘quick and easy’ multi-domain screening prior to cancer treatment. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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13 pages, 291 KiB

Open AccessArticle

by Linda Sharp, Laura-Jayne Watson, Liya Lu, Sam Harding, Katrina Hurley, Steve J. Thomas and Joanne M. Patterson

Cancers 2023, 15(19), 4864; https://doi.org/10.3390/cancers15194864 - 5 Oct 2023

Cited by 2 | Viewed by 1535

Abstract

Cancer-related fatigue (CRF) is a common side-effect of cancer and its treatments. For head and neck cancer (HNC), CRF may exacerbate the symptom burden and poor quality-of-life. Using data from the Head and Neck 5000 prospective clinical cohort, we investigated clinically important CRF over a year post-diagnosis, assessing temporal trends, CRF by HNC site and treatment received, and subgroups at higher risk of CRF. Recruitment was undertaken in 2011–2014. Socio-demographic and clinical data, and patient-reported CRF (EORTC QLQ-C30 fatigue subscale score ≥39 of a possible 100) were collected at baseline (pre-treatment) and 4- and 12- months post-baseline. Mixed-effects logistic multivariable regression was used to investigate time trends, compare cancer sites and treatment groups, and identify associations between clinical, socio-demographic and lifestyle variables and CRF. At baseline, 27.8% of 2847 patients scored in the range for clinically important CRF. This was 44.7% at 4 months and 29.6% at 12 months. In the multivariable model, after adjusting for time-point, the odds of having CRF over 12 months were significantly increased in females and current smokers; those with stage 3/4 disease, comorbidities and multimodal treatment; and those who had depression at baseline. The high prevalence of clinically important CRF indicates the need for additional interventions and supports for affected HNC patients. These findings also identified patient subgroups towards whom such interventions could be targeted. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

15 pages, 606 KiB

Open AccessArticle

Changes in Sexuality and Sexual Dysfunction over Time in the First Two Years after Treatment of Head and Neck Cancer

by Margot A. Stone, Birgit I. Lissenberg-Witte, Remco de Bree, Jose A. Hardillo, Femke Lamers, Johannes A. Langendijk, C. René Leemans, Robert P. Takes, Femke Jansen and Irma M. Verdonck-de Leeuw

Cancers 2023, 15(19), 4755; https://doi.org/10.3390/cancers15194755 - 27 Sep 2023

Cited by 3 | Viewed by 1577

Abstract

The aim of this study was to investigate changes in sexuality and sexual dysfunction in head and neck cancer (HNC) patients in the first two years after treatment, in relation to the type of treatment. Data were used of 588 HNC patients participating in the prospective NETherlands Quality of life and Biomedical Cohort Study (NET-QUBIC) from diagnosis to 3, 6, 12 and 24 months after treatment. Primary outcome measures were the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). The total scores of the IIEF and FSFI were dichotomized into sexual (dys)function. In men, type of treatment was significantly associated with change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction. In women, type of treatment was significantly associated with change in desire, arousal, and orgasm. There were significant differences between treatment groups in change in dysfunctional sexuality. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. Changes in sexuality and sexual dysfunction in HNC patients were related to treatment, with an acute negative effect of chemoradiation. This effect on the various domains of sexuality seems to differ between men and women. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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11 pages, 1478 KiB

Open AccessArticle

Tumor and Nodal Disease Growth Rates in Patients with Oropharyngeal Squamous Cell Carcinoma

by Nicole I. Farber, Yimin Li, Roberto N. Solis, Joy Chen, Zahrah Masheeb, Machelle Wilson, Arnaud F. Bewley, Marianne Abouyared, Shyam Rao, Yi Rong and Andrew C. Birkeland

Cancers 2023, 15(15), 3865; https://doi.org/10.3390/cancers15153865 - 29 Jul 2023

Viewed by 1292

Abstract

Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012–2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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11 pages, 2416 KiB

Open AccessArticle

A Novel Method Using Fine Needle Aspiration from Tumor-Draining Lymph Nodes Could Enable the Discovery of New Prognostic Markers in Patients with Cutaneous Squamous Cell Carcinoma

by Vilma Lagebro, Krzysztof Piersiala, Marianne Petro, Jan Lapins, Per Grybäck, Gregori Margolin, Susanna Kumlien Georén and Lars-Olaf Cardell

Cancers 2023, 15(13), 3297; https://doi.org/10.3390/cancers15133297 - 22 Jun 2023

Cited by 1 | Viewed by 1381

Abstract

Cutaneous squamous cell cancer (cSCC) is the second most common form of skin cancer, characterized by abnormal, accelerated growth of squamous cells. When caught early, most cSCCs are curable. About 5 percent of the cSCC cases have advanced to such an extent, generally metastatic, that they are far more dangerous, with very poor prognosis and challenging to treat. All efforts to find biomarkers, in blood or in the tumor itself, for early identification of patients with a risk for metastasis have so far failed. The present study describes a novel method that enables the identification of lymphocyte markers in tumor-draining lymph nodes. Six patients with advanced cSCC were analyzed using a combination of a sentinel lymph node biopsy (SLNB) protocol, fine needle aspiration (FNA), and flow cytometry. Immunological results from the sentinel nodes were combined with corresponding data from peripheral blood and unfixed tumor tissues. The result demonstrates a striking difference between the subsets of T-cells from the three compartments. Our interpretation of this first pilot study is that the ability to follow specific immunological markers on lymphocytes in tumor-draining lymph nodes will enable the identification of novel prognostic biomarkers not detectable in material from blood and tumor tissues. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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18 pages, 2735 KiB

Open AccessArticle

Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck

by Santiago Cabezas-Camarero, Vanesa García-Barberán, Javier David Benítez-Fuentes, Miguel J. Sotelo, José Carlos Plaza, Alejandro Encinas-Bascones, Óscar De-la-Sen, Farzin Falahat, Jesús Gimeno-Hernández, Manuel Gómez-Serrano, Fernando Puebla-Díaz, Manuel De-Pedro-Marina, Maricruz Iglesias-Moreno and Pedro Pérez-Segura

Cancers 2023, 15(9), 2431; https://doi.org/10.3390/cancers15092431 - 24 Apr 2023

Cited by 1 | Viewed by 1900

Abstract

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min–Max: 31–86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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19 pages, 961 KiB

Open AccessArticle

Subgroup Analysis of Overall Survival among Smoking and Non-Smoking Elderly Patients with HNSCC

by Raphaela Graessle, Carmen Stromberger, Marcus Beck, Max Heiland, Veit M. Hofmann, Heidi Olze, Steffen Dommerich, Ulrich Gauger, Iris Piwonski and Annekatrin Coordes

Cancers 2023, 15(6), 1842; https://doi.org/10.3390/cancers15061842 - 19 Mar 2023

Viewed by 1661

Abstract

Smoking is a leading cause of head and neck squamous cell carcinoma (HNSCC). However, non-smokers are also affected by HNSCC, and the prognostic factors applicable to older non-smokers with HNSCC are largely unknown. The aim of this study was to determine predictors of overall survival (OS) in patients both with and without a smoking history aged 70 and over at initial diagnosis. Retrospective data of patients aged ≥70 (initial diagnoses 2004–2018) were examined. Evaluated predictors included tumour stage, biological age, health and therapy. A total of 688 patients (520 smokers, 168 non-smokers) were included with a median age of 74. The 5-year OS was 39.6%. Non-smokers had significantly improved OS compared to smokers (52.0% versus 36.0%, p < 0.001). Disease-free survival (DFS) differed significantly between both groups (hazard ratio = 1.3; 95%CI 1.04–1.626). TNM stage and the recommended therapies (curative versus palliative) were comparable. The proportion of p16-positive oropharyngeal carcinomas was significantly higher in non-smokers (76.7% versus 43.8%, p < 0.001). Smokers were significantly more likely to be men (p < 0.001), drinkers (p < 0.001), and have poorer health status (Karnofsky performance status, KPS, p = 0.023). They were also more likely to have additional tumours (p = 0.012) and lower treatment adherence (p = 0.038). Important predictors of OS identified in both groups, were, among others, alcohol abuse, KPS, Charlson comorbidity index, site of primary tumour, UICC stage and treatment received. Elderly non-smokers are also affected by HNSCC, however, both OS and DFS are increased compared to smokers. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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16 pages, 2966 KiB

Open AccessArticle

A Novel Subgroup of UCHL1-Related Cancers Is Associated with Genomic Instability and Sensitivity to DNA-Damaging Treatment

by Sebastian Burkart, Christopher Weusthof, Karam Khorani, Sonja Steen, Fabian Stögbauer, Kristian Unger, Julia Hess, Horst Zitzelsberger, Claus Belka, Ina Kurth and Jochen Hess

Cancers 2023, 15(6), 1655; https://doi.org/10.3390/cancers15061655 - 8 Mar 2023

Cited by 1 | Viewed by 2190

Abstract

Purpose: Identification of molecularly-defined cancer subgroups and targeting tumor-specific vulnerabilities have a strong potential to improve treatment response and patient outcomes but remain an unmet challenge of high clinical relevance, especially in head and neck squamous cell carcinoma (HNSC). Experimental design: We established a UCHL1-related gene set to identify and molecularly characterize a UCHL1-related subgroup within TCGA-HNSC by integrative analysis of multi-omics data. An extreme gradient boosting model was trained on TCGA-HNSC based on GSVA scores for gene sets of the MSigDB to robustly predict UCHL1-related cancers in other solid tumors and cancer cell lines derived thereof. Potential vulnerabilities of UCHL1-related cancer cells were elucidated by an in-silico drug screening approach. Results: We established a 497-gene set, which stratified the TCGA-HNSC cohort into distinct subgroups with a UCHL1-related or other phenotype. UCHL1-related HNSC were characterized by higher frequencies of genomic alterations, which was also evident for UCHL1-related cancers of other solid tumors predicted by the classification model. These data indicated an impaired maintenance of genomic integrity and vulnerability for DNA-damaging treatment, which was supported by a favorable prognosis of UCHL1-related tumors after radiotherapy, and a higher sensitivity of UCHL1-related cancer cells to irradiation or DNA-damaging compounds (e.g., Oxaliplatin). Conclusion: Our study established UCHL1-related cancers as a novel subgroup across most solid tumor entities with a unique molecular phenotype and DNA-damaging treatment as a specific vulnerability, which requires further proof-of-concept in pre-clinical models and future clinical trials. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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14 pages, 9485 KiB

Open AccessArticle

Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets

by Hélios Bertin, Sophie Peries, Jérôme Amiaud, Nathalie Van Acker, Bastien Perrot, Corinne Bouvier, Sébastien Aubert, Béatrice Marie, Frédérique Larousserie, Gonzague De Pinieux, Vincent Crenn, Françoise Rédini and Anne Gomez-Brouchet

Cancers 2023, 15(4), 1004; https://doi.org/10.3390/cancers15041004 - 4 Feb 2023

Cited by 4 | Viewed by 1830

Abstract

Background—The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods—We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs). We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1). The biomarkers were analyzed for their influence on progression (recurrence and metastasis), overall survival (OS), and disease-free survival (DFS). Results—A strong and significant correlation has been found between CD163 staining and lower OS and DFS. The level of CD4+ and CD8+ staining was low and non-significantly associated with survival outcomes. High levels of RANK and RANKL were found in the tumor samples and correlated with lower DFS. Conclusion—Our findings suggest that CD163+ TAMs represent markers of poor prognosis in JO. Targeting TAMs could represent a valuable therapeutic strategy in JO. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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Review

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19 pages, 1228 KiB

Open AccessReview

Statins in Cancer Prevention and Therapy

by Natalia Ricco and Stephen J. Kron

Cancers 2023, 15(15), 3948; https://doi.org/10.3390/cancers15153948 - 3 Aug 2023

Cited by 11 | Viewed by 2863

Abstract

Statins, a class of HMG-CoA reductase inhibitors best known for their cholesterol-reducing and cardiovascular protective activity, have also demonstrated promise in cancer prevention and treatment. This review focuses on their potential applications in head and neck cancer (HNC), a common malignancy for which established treatment often fails despite incurring debilitating adverse effects. Preclinical and clinical studies have suggested that statins may enhance HNC sensitivity to radiation and other conventional therapies while protecting normal tissue, but the underlying mechanisms remain poorly defined, likely involving both cholesterol-dependent and -independent effects on diverse cancer-related pathways. This review brings together recent discoveries concerning the anticancer activity of statins relevant to HNC, highlighting their anti-inflammatory activity and impacts on DNA-damage response. We also explore molecular targets and mechanisms and discuss the potential to integrate statins into conventional HNC treatment regimens to improve patient outcomes. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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17 pages, 899 KiB

Open AccessReview

Practical Application of Circulating Tumor-Related DNA of Human Papillomavirus in Liquid Biopsy to Evaluate the Molecular Response in Patients with Oropharyngeal Cancer

by Agnieszka M. Mazurek and Tomasz W. Rutkowski

Cancers 2023, 15(4), 1047; https://doi.org/10.3390/cancers15041047 - 7 Feb 2023

Cited by 3 | Viewed by 2099

Abstract

Recent findings have shown that human papillomavirus (HPV) DNA is present in the blood as a tumor-specific biomarker (circulating tumor-related HPV; ctHPV) in patients with HPV-related oropharyngeal cancer (HPV-related OPC). The molecular response (MR) in patients with HPV-related OPC can be defined as the change in the number of ctHPV copies in relation to its initial quantity. The optimal model for assessing the MR using a liquid biopsy (LB) should be based on the E6/E7 sequences of the viral genome. MR assessment can help to evaluate the intensity of ongoing treatments in relation to the tumor response. The evaluation of the residual disease at the end of therapy may also be performed by MR assessment. If a partial MR (pMR) is found, caution is indicated and a subsequent LB should be considered, due to the likelihood of disease progression. Complete radiological and clinical responses together with a complete MR (cMR) convincingly indicate a low risk of treatment failure. Moreover, molecular recurrence (Mrec) during a follow-up, confirmed in two consecutive assays, even despite the lack of any other clinical or radiological symptoms of progression, indicates patients at high risk of disease recurrence. In conclusion, MR by ctHPV assessment may hasten the early detection of disease progression, at any stage of the management of the patient with HPV-related OPC. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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25 pages, 2458 KiB

Open AccessSystematic Review

The Prediction of Biological Features Using Magnetic Resonance Imaging in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

by Hedda J. van der Hulst, Robin W. Jansen, Conchita Vens, Paula Bos, Winnie Schats, Marcus C. de Jong, Roland M. Martens, Zuhir Bodalal, Regina G. H. Beets-Tan, Michiel W. M. van den Brekel, Pim de Graaf and Jonas A. Castelijns

Cancers 2023, 15(20), 5077; https://doi.org/10.3390/cancers15205077 - 20 Oct 2023

Cited by 1 | Viewed by 2038

Abstract

Magnetic resonance imaging (MRI) is an indispensable, routine technique that provides morphological and functional imaging sequences. MRI can potentially capture tumor biology and allow for longitudinal evaluation of head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis evaluates the ability of MRI to predict tumor biology in primary HNSCC. Studies were screened, selected, and assessed for quality using appropriate tools according to the PRISMA criteria. Fifty-eight articles were analyzed, examining the relationship between (functional) MRI parameters and biological features and genetics. Most studies focused on HPV status associations, revealing that HPV-positive tumors consistently exhibited lower ADC_mean (SMD: 0.82; p < 0.001) and ADC_minimum (SMD: 0.56; p < 0.001) values. On average, lower ADC_mean values are associated with high Ki-67 levels, linking this diffusion restriction to high cellularity. Several perfusion parameters of the vascular compartment were significantly associated with HIF-1α. Analysis of other biological factors (VEGF, EGFR, tumor cell count, p53, and MVD) yielded inconclusive results. Larger datasets with homogenous acquisition are required to develop and test radiomic-based prediction models capable of capturing different aspects of the underlying tumor biology. Overall, our study shows that rapid and non-invasive characterization of tumor biology via MRI is feasible and could enhance clinical outcome predictions and personalized patient management for HNSCC. Full article

(This article belongs to the Special Issue 2nd Edition: Targeting Head and Neck Cancer)

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