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Advances in Squamous Cell Carcinoma of the Head and Neck

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A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Head and Neck Oncology".

Deadline for manuscript submissions: closed (1 November 2022) | Viewed by 42044

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Dr. Dimitra P. Vageli

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The Yale Larynx Laboratory, Department of Surgery (Otolaryngology), Yale School of Medicine, New Haven, CT 06510, USA
Interests: bile reflux; carcinogens; NF-kappa B; STAT3 transcription factor; DNA mismatch repair; laryngopharyngeal reflux; squamous cell carcinoma of head and neck

Special Issue Information

Dear Colleagues,

Head and neck cancer account for about 4% of all cancers in The United States. However, it is estimated that approximately 66,630 new cases (48,740 men and 17,890 women) and 14,620 deaths (10,640 men and 3980 women) from head and neck cancer will occur in the United States in 2021. From a clinical perspective, laryngopharyngeal tumors, which account for almost 50% of all head and neck cancers (HNSCC), are very aggressive, causing high levels of functional morbidity and mortality, with an overall 5-year survival rate of approximately 60% and are therefore considered among the most devastating cancers. Known risk factors, such as smoking, alcohol consumption, and HPV16 infection have been associated with HNSCC. Additional risk factors, such as laryngopharyngeal reﬂux (LPR), have also been linked to the disease. The pathogenesis of HNSCC and its therapeutic targeting strategies require further investigation. Identifying and characterizing the mechanism of the neoplastic process that is activated under the influence of variable risk factors would ultimately allow a more comprehensive risk stratiﬁcation and prevention of HNSCC, such as laryngopharyngeal cancer or its recurrences, including the development of therapeutic strategies.

In this Special Issue of Current Oncology, we invite research reports focused on new advances on head and neck squamous cell carcinoma (HNSCC) risk factors, prevention, and novel therapy; specifically, these topics may include:

HNSCC epidemiology;
HNSCC etiopathogenesis and prevention;
HNSCC novel targets and biomarkers;
Advances of HNSCC therapeutic strategies.

Dr. Dimitra P. Vageli
Guest Editor

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Keywords

head and neck carcinogenesis
laryngopharyngeal cancer
hypopharyngeal cancer
cause, prevention, and therapy

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Published Papers (12 papers)

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Research

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9 pages, 1328 KiB

Open AccessArticle

Matrix for Mucosal Regeneration in Transoral Glossectomy for Squamous Cell Carcinoma: Objective and Subjective Functional Evaluation

by Alberto Deganello, Paolo Bosio, Lorenzo Giannini, Federico Parolini, Giulia Berretti, Alessandra Sordi, Vittorio Rampinelli and Tommaso Gualtieri

Curr. Oncol. 2023, 30(2), 1354-1362; https://doi.org/10.3390/curroncol30020104 - 17 Jan 2023

Cited by 2 | Viewed by 2895

Abstract

Background: Numerous options to manage local reconstruction following transoral partial glossectomy are possible. In this work, we present our experience using a matrix for mucosal regeneration, Integra^®, after transoral resections of squamous cell carcinoma of the oral tongue. Methods: A retrospective analysis of patients treated for tongue carcinoma and reconstruction with Integra^®, from September 2017 to September 2022. Functional outcomes were evaluated by measuring swallowing and speech abilities, tongue motility, and subjective quality of life. Results: The series accounts for 13 consecutive patients, staged from Tis to T3, no positive resection margins were found, average defect size was 17.8 cm². The average histologically measured depth of invasion was 4.1 mm (range 2–12 mm), and no recurrences were observed during follow-up. All patients maintained excellent swallowing function, the average number of recognized words by an external listener during a phone call was 70.5 out of 75, the lingual motility test was good (a mean score of 4.5 out of 6 movements correctly executed) and subjective questionnaires results were optimal. Less satisfying functional results were recorded in elderly patients receiving a wider surgical resection. Conclusions: This reconstructive technique for allows obtaining optimal healing and functional outcomes in patients with tumors suitable for transoral glossectomy. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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12 pages, 5602 KiB

Open AccessArticle

Management of Parapharyngeal Space Tumors: Clinical Experience with a Large Sample and Review of the Literature

by Chuanya Jiang, Wenqian Wang, Shanwen Chen and Yehai Liu

Curr. Oncol. 2023, 30(1), 1020-1031; https://doi.org/10.3390/curroncol30010078 - 11 Jan 2023

Cited by 4 | Viewed by 3184

Abstract

Parapharyngeal space (PPS) tumors are rare, and they account for 0.5–1.5% of all head and neck tumors. This study summarized the findings of large-sample clinical studies of PPS tumors and reported the clinical work-up and management of 177 cases of PPS tumors at our center. This retrospective study included patients treated for PPS tumors between 2005 and 2020 at our center. The basic characteristics, symptoms, surgical approach, complications, and recurrence rates were analyzed. A total of 99 male and 78 female patients, with a mean age of 48.3 ± 15.1 years, were enrolled in this study. The most common symptoms were external or intraoral masses (114 patients, 64%). Surgical management leveraging, a cervical approach, was used for 131 cases (74%). The tumors were benign for 92% (160 cases), with pleomorphic adenoma being the most common (88 cases, 50%). Surgical complications were reported for 31 cases (18%); facial and vocal cord paralyses were the most common. Three cases of recurrence were observed during the follow-up. PPS tumors are rare and present with atypical clinical manifestations. The current study, which involved cases in a large single center, demonstrates the importance of surgical interventions for PPS tumors. The use of endoscopic techniques has further expanded the scope of traditional surgical approaches and demonstrated its advantages in selected cases. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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11 pages, 1923 KiB

Open AccessArticle

RIOK2 Contributes to Cell Growth and Protein Synthesis in Human Oral Squamous Cell Carcinoma

by Yusuke Matsuzaki, Yutaka Naito, Nami Miura, Taisuke Mori, Yukio Watabe, Seiichi Yoshimoto, Takahiko Shibahara, Masayuki Takano and Kazufumi Honda

Curr. Oncol. 2023, 30(1), 381-391; https://doi.org/10.3390/curroncol30010031 - 26 Dec 2022

Cited by 1 | Viewed by 2540

Abstract

Ribosomes are responsible for the protein synthesis that maintains cellular homeostasis and is required for the rapid cellular division of cancer cells. However, the role of ribosome biogenesis mediators in the malignant behavior of tongue squamous cell carcinoma (TSCC) is unknown. In this study, we found that the expression of RIOK2, a key enzyme involved in the maturation steps of the pre-40S ribosomal complex, was significantly associated with poorer overall survival in patients with TSCC. Further, multivariate analysis revealed that RIOK2 is an independent prognostic factor (hazard ratio, 3.53; 95% confidence interval, 1.19–10.91). Inhibition of RIOK2 expression by siRNA decreased cell growth and S6 ribosomal protein expression in oral squamous cell carcinoma cell lines. RIOK2 knockdown also led to a significant decrease in the protein synthesis in cancer cells. RIOK2 has potential application as a novel therapeutic target for TSCC treatment. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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14 pages, 2744 KiB

Open AccessArticle

Predicting Nomogram for Severe Oral Mucositis in Patients with Nasopharyngeal Carcinoma during Intensity-Modulated Radiation Therapy: A Retrospective Cohort Study

by Zhibing Liu, Lulu Huang, Housheng Wang, Zhiling Shi, Yaqin Huang, Lixing Liang, Rensheng Wang and Kai Hu

Curr. Oncol. 2023, 30(1), 219-232; https://doi.org/10.3390/curroncol30010017 - 23 Dec 2022

Cited by 10 | Viewed by 2286

Abstract

Background: Oral mucositis is an acute adverse reaction with high incidence during radiotherapy. Severe oral mucositis can seriously affect patients’ quality of life and compliance with radiotherapy. The aim of this study was to identify the risk factors for severe oral mucositis and to develop a nomogram for predicting severe oral mucositis in patients with nasopharyngeal carcinoma. Methods: One hundred and ninety patients with nasopharyngeal carcinoma were retrospectively screened in this study. Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were performed to identify the best predictors of severe oral mucositis. A nomogram was constructed based on the factors. Finally, the discriminative ability of the nomogram was evaluated. Results: Four independent factors predicting severe oral mucositis were identified: age, N stage, the cycle of induction chemotherapy, and dose-volumetric parameter V40 (%) of oral cavity. The area under the receiver of operating characteristic curve of the nomogram was 0.759 (95% confidence interval: 0.691–0.827). Conclusions: A predictive nomogram for severe oral mucositis was established and validated in this study. The nomogram provides a reliable and practical model for clinically predicting the probability of severe oral mucositis in patients with nasopharyngeal carcinoma before intensity-modulated radiation therapy. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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20 pages, 26710 KiB

Open AccessArticle

Zinc Finger Proteins in Head and Neck Squamous Cell Carcinomas: ZNF540 May Serve as a Biomarker

by Joanna Sobocińska, Joanna Nowakowska, Sara Molenda, Anna Olechnowicz, Kacper Guglas, Joanna Kozłowska-Masłoń, Urszula Kazimierczak, Marta Machnik, Urszula Oleksiewicz, Anna Teresiak, Katarzyna Lamperska and Tomasz Kolenda

Curr. Oncol. 2022, 29(12), 9896-9915; https://doi.org/10.3390/curroncol29120779 - 16 Dec 2022

Cited by 5 | Viewed by 2680

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers. Most cancer cases originate from alcohol and tobacco consumption. However, studies have demonstrated that human papillomavirus (HPV) infection, particularly HPV-16, may also significantly influence disease progression. The KRAB-ZNF family of genes is involved in epigenetic suppression, and its involvement in carcinogenesis is the subject of extensive studies. The available literature data demonstrate that they may play different roles, both as tumor suppressors and oncogenes. In this study, six ZNF genes, ZFP28, ZNF132, ZNF418, ZNF426, ZNF540, and ZNF880, were tested using several in silico approaches based on the TCGA and GEO datasets. Our analyses indicate that the expression of the analyzed ZNFs was significantly downregulated in tumor tissues and depended on tumor localization. The expression levels of ZNFs differed between HPV-positive vs. HPV-negative patients depending on the clinical-pathological parameters. More specifically, the patients with higher levels of ZNF418 and ZNF540 showed better survival rates than those with a lower expression. In addition, the level of ZNF540 expression in HPV-positive (HPV(+)) patients was higher than in HPV-negative (HPV(−)) patients (p < 0.0001) and was associated with better overall survival (OS). In conclusion, we demonstrate that ZNF540 expression highly correlates with HPV infection, which renders ZNF540 a potential biomarker for HNSCC prognosis and treatment. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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13 pages, 3080 KiB

Open AccessFeature PaperArticle

A Study of Peripheral Blood Parameters to Predict Response to Induction Chemotherapy and Overall Survival in Advanced Laryngeal Squamous Cell Carcinoma

by Jiaqi Xu, Yifan Yang, Qi Zhong, Lizhen Hou, Hongzhi Ma, Yang Zhang, Ling Feng, Shizhi He, Meng Lian, Jugao Fang and Ru Wang

Curr. Oncol. 2022, 29(9), 6472-6484; https://doi.org/10.3390/curroncol29090509 - 9 Sep 2022

Cited by 4 | Viewed by 1932

Abstract

Purpose: the purpose of this study was to screen peripheral blood parameters and construct models predicting the prognosis and induction chemotherapy (IC) response in locally advanced laryngeal squamous cell carcinoma (LSCC) patients. Methods: A total of 128 stage III/IVa LSCC patients (who required a total laryngectomy) were enrolled in a retrospective study from January 2013 to September 2020 at Beijing Tongren Hospital of Capital Medical University. Among them, 62 patients received IC (IC group), and 66 patients immediately underwent a total laryngectomy (TL) after diagnosis (surgery group). Demographic information and peripheral blood parameters were collected for further analysis. The overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) were compared between the two groups. The prognosis and survival were also compared between patients with laryngeal function preservation (LFP) and those with TL. Results: The Receiver Operating Characteristic (ROC) curve for IC response in the IC group showed that the AUC of the blood model based on the four peripheral blood parameters of fibrinogen (FIB), platelet (PLT), high-density lipoprotein cholesterol (HDL), and albumin (ALB) was significantly higher than the TNM stage model’s AUC (0.7932 vs. 0.6568). We constructed a nomogram blood model to predict IC response (C-Index = 0.793). Regarding the OS of all patients, an ROC analysis for overall survival, the Kaplan–Meier (K-M) method with a log-rank test, and multivariate analysis indicated age, clinical stage, FIB, and hemoglobin (HGB) were independent prognostic factors for the OS of LSCC patients. The blood–clinical logistic model (AUC = 0.7979) was constructed based on the four prognosis factors, which were superior to the blood (AUC = 0.6867) or clinical models (AUC = 0.7145) alone to predict OS. We constructed a nomogram model based on age, clinical stage, FIB, and HGB to predict OS for LSCC patients (C-Index = 0.792). Besides this, there were no significant differences in OS, PFS, and DSS between IC and surgery groups or LFP and TL groups. Conclusion: Peripheral blood parameters help predict IC response and overall survival. Furthermore, induction chemotherapy significantly improves laryngeal function preservation without lowering the survival prognosis. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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19 pages, 7108 KiB

Open AccessArticle

The Effect of Tobacco Smoke N-Nitrosamines, NNK and NDEA, and Nicotine, on DNA Mismatch Repair Mechanism and miRNA Markers, in Hypopharyngeal Squamous Cell Carcinoma: An In Vivo Model and Clinical Evidence

by Sotirios G. Doukas, Dimitra P. Vageli, Panagiotis G. Doukas, Dragana Nikitovic, Aristidis Tsatsakis and Benjamin L. Judson

Curr. Oncol. 2022, 29(8), 5531-5549; https://doi.org/10.3390/curroncol29080437 - 4 Aug 2022

Cited by 8 | Viewed by 2992

Abstract

Deregulation of the DNA mismatch repair (MMR) mechanism has been linked to poor prognosis of upper aerodigestive tract cancers. Our recent in vitro data have provided evidence of crosstalk between deregulated miRNAs and MMR genes, caused by tobacco smoke (TS) N-Nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in hypopharyngeal cells. Here, we explored whether chronic exposure to TS components can affect MMR mechanism and miRNA profiles in hypopharyngeal mucosa. Using a mouse model (C57Bl/6J wild type) of in vivo 14-week exposure to NNK (0.2 mmol/L) and N-Nitrosodiethylamine (NDEA; 0.004 mmol/L), with or without nicotine (0.02 μmol/L), we provide direct evidence that TS components can promote dysplasia, significant downregulation of Msh2 and Mlh1 genes and deregulation of miR-21, miR-155, miR-34a, and miR-451a. By analyzing eight human specimens from tobacco smokers and eight controls, we provide clinical evidence of a significant reduction in hMSH2 and hMLH1 mRNAs in hypopharyngeal squamous cell carcinoma (HSCC). In summary, deregulation of the MMR mechanism and miRNAs is caused by chronic exposure to TS-related N-Nitrosamines, with or without nicotine, in the early stages of upper aerodigestive tract carcinogenesis, and can also be detected in human HSCC. Thus, we encourage future studies to further elucidate a possible in vivo dose-dependent effect of individual or combined N-Nitrosamines, NNK and/or NDEA, and nicotine, on the MMR mechanism and their clinical testing to elaborate prognosis and risk assessment. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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Review

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14 pages, 587 KiB

Open AccessReview

Oral Squamous Cell Carcinoma and Concomitant Primary Tumors, What Do We Know? A Review of the Literature

by Mohammed Badwelan, Hasan Muaddi, Abeer Ahmed, Kyungjun T. Lee and Simon D. Tran

Curr. Oncol. 2023, 30(4), 3721-3734; https://doi.org/10.3390/curroncol30040283 - 27 Mar 2023

Cited by 50 | Viewed by 8373

Abstract

Head and neck cancer is among the top ten cancers worldwide, with most lesions in the oral cavity. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral malignancies and is a significant public health concern. Patients with OSCC are at increased risk for developing concomitant tumors, especially in the oral cavity, due to widely genetically susceptible mucosa to carcinogenic factors. Based on fulfilling specific criteria, these concomitant tumors can be called second primary tumors (SPTs), which can be further categorized into metachronous and synchronous tumors. This research reviews the literature that investigated the concurrent OSCC with second or multiple primaries to improve understanding of the definition, classification guidelines, and its effect on cancer survival. It also highlights the current investigation methods, the variation of standard treatment approaches due to such a phenomenon, and preventive measures discussed in the literature. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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12 pages, 1574 KiB

Open AccessReview

Transoral Approach to Parotid Tumors: A Review of the Literature

by Giuseppe Riva, Andrea Lorenzi, Andrea Borello, Andrea Albera, Andrea Canale and Giancarlo Pecorari

Curr. Oncol. 2022, 29(12), 9416-9427; https://doi.org/10.3390/curroncol29120740 - 1 Dec 2022

Cited by 4 | Viewed by 4450

Abstract

Different surgical techniques have been proposed for parapharyngeal space tumors, including transcervical, transparotid, trans-mandibular, infratemporal, and transoral. The choice of the correct approach depends on the size, localization and nature of the tumor. The transoral approach can be used for benign prestyloid masses, such as tumors of the deep lobe of the parotid gland. It guarantees a short hospitalization without skin scars. The narrowed access represents the main limitation of this technique. This review will summarize and analyze the current knowledge about the transoral approach to parotid lesions. Thirty-seven studies were included in a qualitative and quantitative synthesis. The novelty of this review is the quantitative analyses of the clinical data reported in the included studies. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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14 pages, 629 KiB

Open AccessReview

Current and Future Biomarkers for Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma

by Jong Chul Park, Hari N. Krishnakumar and Srinivas Vinod Saladi

Curr. Oncol. 2022, 29(6), 4185-4198; https://doi.org/10.3390/curroncol29060334 - 8 Jun 2022

Cited by 21 | Viewed by 4319

Abstract

With the introduction of immunotherapy, significant improvement has been made in the treatment of head and neck squamous cell carcinoma (HNSCC). However, only a small subset of patients with HNSCC benefit from immunotherapy. The current biomarker, a programmed cell death protein ligand 1 (PD-L1) expression that is widely used in treatment decision making for advanced HNSCC, has only a moderate predictive value. Additionally, PD-L1-based assay has critical inherent limitations due to its highly dynamic nature and lack of standardization. With the advance in molecular techniques and our understanding of biology, more reliable, reproducible, and practical novel biomarkers are being developed. These include but are not limited to neoantigen/mutation characteristics, immune transcriptomes, tumor-infiltrating immune cell composition, cancer epigenomic, proteomics and metabolic characteristics, and plasma-based and organoid assays. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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18 pages, 377 KiB

Open AccessReview

Micro-RNAs, the Cornerstones of the Future of Radiobiology in Head and Neck Cancers?

by Camil Ciprian Mireștean, Roxana Irina Iancu and Dragoș Petru Teodor Iancu

Curr. Oncol. 2022, 29(2), 816-833; https://doi.org/10.3390/curroncol29020069 - 2 Feb 2022

Cited by 5 | Viewed by 2663

Abstract

Even though it is only the 6th most common malignancy at the modal level, head and neck cancers are distinguished by a considerable treatment failure rate, especially by locoregional recurrences, the intrinsic tumor radioresistance being one of the causes of this phenomenon. The efforts of radiobiological research of these cancers are oriented towards the identification of biomarkers associated with radioresistance and radiosensitivity in order to modulate the treatment so that the therapeutic benefit is maximum. Micro-RNAs (miRNAs, miRs), small single-stranded non-coding RNA molecules are currently being extensively evaluated as potential biomarkers in numerous diseases, including cancer. The evaluation of the potential of miRNAs to modulate or predict radiosensitivity or radioresistance, to anticipate the risk of recurrence and metastasis, and to differentiate different tumor subtypes is based on multiple mechanisms by which mRNAs control proliferation and apoptosis and interact with cell cycle phases or act as oncogenes with the potential to influence invasion promotion or tumor suppression. A refinement of radiosensitivity based on miRNAs with clinical and radiobiological application in head and neck cancers can lead to a personalization of radiotherapy. Thus, a miRNA signature can anticipate the risk of toxicity associated with chemoradiation, the possibility of obtaining locoregional control after treatment, and the recurrence and distant metastasis risk. The potential of miRNAs as an intrinsic predictor of sensitivity to chemotherapy may also guide the therapeutic decision toward choosing an escalation or de-escalation of concurrent or sequential systemic treatment. The choice of the irradiated dose, the fractional dose, the fractionation scheme, and the refining of the dose-volume constraints depending on the radiosensitivity of each tissue type estimated on a case-by-case basis by miRNAs profile are possible concepts for the future radiotherapy and radiobiology of head and neck cancers. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

Other

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10 pages, 704 KiB

Open AccessSystematic Review

The Use of Contrast-Enhanced Sonography for Therapy Monitoring of Metastatic Lymph Nodes: A Systematic Review

by Maximilian Rink, Ernst-Michael Jung and Julian Künzel

Curr. Oncol. 2023, 30(7), 6734-6743; https://doi.org/10.3390/curroncol30070494 - 16 Jul 2023

Viewed by 1679

Abstract

Metastatic cervical lymph nodes are a frequent finding in head and neck squamous cell carcinoma (HNSCC). If a non-surgical approach is primarily chosen, a therapy response evaluation of the primary tumor and the affected lymph nodes is necessary in the follow-up. Supplementary contrast-enhanced ultrasound (CEUS) can be used to precisely visualize the microcirculation of the target lesion in the neck, whereby malignant and benign findings differ in their uptake behavior. The same applies to many other solid tumors. For various tumor entities, it has already been shown that therapy monitoring is possible through regular contrast-enhanced sonography of the primary tumor or the affected lymph nodes. Thus, in some cases, maybe in the future, a change in therapy strategy can be achieved at an early stage in the case of non-response or, in the case of therapy success, a de-escalation of subsequent (surgical) measures can be achieved. In this paper, a systematic review of the available studies and a discussion of the potential of therapy monitoring by means of CEUS in HNSCC are presented. Full article

(This article belongs to the Special Issue Advances in Squamous Cell Carcinoma of the Head and Neck)

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