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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Clinical Diagnosis and Prognosis".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 19100

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Special Issue Editors

Prof. Dr. Nina Gale

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Guest Editor

Institute of Pathology, Faculty of Medicine, Korytkova 2, 1000 Ljubljana, Slovenia.
Interests: head and neck tumors; narrow band imaging; oropharyngeal neoplasms

Prof. Dr. Primož Strojan

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Guest Editor

Department of Radiation Oncology, Institute of Oncology, Zaloška 2, 1000 Ljubljana, Slovenia
Interests: head and neck cancer; neuroendocrine neoplasms of the head and neck; melanoma and non-melanoma skin cancer; radiochemotherapy; radiotherapy-related toxicities
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Dr. Robert Šifrer

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Guest Editor

Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia
Interests: head and neck cancer; otorhinolaryngology

Special Issue Information

Dear Colleagues,

Among all cancers, head and neck cancer (HNC) ranks sixth in frequency. Due to the complexity of the head and neck region, HNC might cause many symptoms and clinical signs. Curative organ-sparing procedures encompass various irradiation or chemoradiotherapy protocols. In contrast, curative surgical treatment ranges from conservative surgery (i.e., endoscopic or open partial laryngectomy, endoscopic resection of sinonasal cancer, sleeve resection of the external auditory canal) to extensive surgical procedures (i.e., total laryngectomy, pharyngectomy, radical maxillectomy, temporal bone resection, complex reconstruction). The type of treatment is always multidisciplinary and has to be accepted by hosting multi-board discussions. It depends on the tumor (histology, extension, disfunction) and patient factors (general conditions, previous treatments, personal preferences). Therefore, the decision is not always straightforward and easy, but it is complex and well thought out.

The importance of the diagnostics of HNC cannot be over emphasized. With the advent of modern endoscopes, surgical microscopes, advanced imaging, enhanced endoscopy, enhanced contact endoscopy, advances in anesthesiology in recent decades, and artificial intelligence in recent years, diagnostics has made an important advancement. All these improvements lead to a more thorough delineation of the extension of cancer and adequate planning of therapy. Nevertheless, they serve our patients the most, after all.

Authors are kindly invited and encouraged to upload their original manuscripts about their experiences and research in the field of diagnostics in otorhinolaryngology in regard to HNC for this Special Issue of Diagnostics.

Prof. Dr. Nina Gale
Prof. Dr. Primož Strojan
Dr. Robert Šifrer
Guest Editors

Manuscript Submission Information

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Keywords

head and neck cancer
otorhinolaryngology
symptoms and clinical signs

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Published Papers (8 papers)

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Research

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14 pages, 1613 KB

Open AccessArticle

Adaptation and Implementation of the Dysphagia and Dysphonia Inventory (HSS-DDI) in Greek Patients After Anterior Surgical Removal of the Herniated Cervical Spine

by Soultana Papadopoulou, Aliki I. Venetsanopoulou, Avraam Ploumis, Kalliopi Megari, Evaggelia-Maria Perivolioti, Nikoleta Tsipa, Andreas Zygouris and Spyridon Voulgaris

Diagnostics 2025, 15(16), 1994; https://doi.org/10.3390/diagnostics15161994 - 9 Aug 2025

Cited by 1 | Viewed by 3458

Abstract

Background: Anterior cervical discectomy and fusion (ACDF) is a widely performed surgical intervention for cervical spine herniation (CSH) to alleviate symptoms such as pain, weakness, and restricted mobility. Despite its efficacy, ACDF is associated with postoperative complications, notably dysphagia and dysphonia (PDD). Objective: This study investigates the prevalence, severity, and risk factors associated with PDD following ACDF using the validated Dysphagia and Dysphonia Inventory (HSS-DDI) adapted into Greek. Methods: A prospective observational cohort study was conducted at the University General Hospital of Ioannina from May to November 2023. The study involved 40 adult patients who underwent ACDF for CSH. Postoperative dysphagia and dysphonia were assessed using the Ohkuma questionnaire and HSS-DDI at 1 week and 1 month postoperatively. Results: The mean age of participants was 54.78 years, with a majority being male (60%). In terms of body mass index (BMI), 30% of participants had a normal weight, 47.5% were overweight, and 22.5% were obese. This study revealed that dysphagia and dysphonia were common postoperative complications, with improvements noted after one month. Factors such as BMI were statistically significant in influencing dysphagia outcomes, with normal BMI individuals reporting better outcomes than obese participants. Confirmatory factor analysis indicated the need for a larger sample size to confirm subscale validity in the Greek population. Conclusions: Postoperative dysphagia and dysphonia are prevalent following ACDF, but most patients experience improvements within a short period. Identifying risk factors, such as BMI, and utilizing validated assessment tools like the HSS-DDI can help optimize surgical techniques and postoperative care. Further studies with larger sample sizes are recommended for a more comprehensive understanding of these complications. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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11 pages, 1012 KB

Open AccessArticle

Accuracy of COuGH RefluX Score as a Predictor of Gastroesophageal Reflux Disease (GERD) in Mexican Patients with Chronic Laryngopharyngeal Symptoms: A Cross-Sectional Study

by Javier Ivanovychs Carrillo-Rojas, Salvador Zavala-Villegas, Guadalupe Morales-Osorio, Fausto Daniel García-García, Mauricio González-Navarro, Viridiana Montsserrat Mendoza-Martínez and Nallely Bueno-Hernández

Diagnostics 2025, 15(5), 636; https://doi.org/10.3390/diagnostics15050636 - 6 Mar 2025

Cited by 1 | Viewed by 3429

Abstract

Background/Objectives: Gastroesophageal reflux disease (GERD) is associated with extraesophageal syndromes that require an objective assessment of abnormal acid exposure to establish the diagnosis. The COuGH RefluX score has been proposed as a diagnostic tool for GERD in patients with chronic laryngopharyngeal symptoms. The aim of the study was to evaluate the diagnostic performance of the COuGH RefluX score in the Mexican population. Methods: A cross-sectional study was conducted in patients with chronic laryngopharyngeal symptoms. Patients with cough, globus, sore throat, dysphonia, and/or throat clearing of ≥8 weeks duration, 24 h pH-impedance monitoring (pH-IM), and without objective evidence of GERD (defined as acid exposure time >6%) were included in the study. The COuGH RefluX score tool was applied and stratified as low probability with ≤2.5 points, intermediate probability with 3.0 to 4.5 points, and high probability with ≥5.0 points. The kappa test assessed the concordance between both tests; the area under the curve (AUR), sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive value (NPV) were calculated for each result. Results: 164 patients were included; the prevalence of GERD by pH-IM was 32% vs. 40.3% by COuGH RefluX score, the agreement was weak (κ = 0.34; p < 0.001), but the AUR was good (0.720 ± 0.17; p < 0.001). A score ≤ 2.5 had S = 49%, E = 88%, PPV = 89%, and NPV = 42% to rule out proven GERD, while a score ≥ 5 had S = 65%, E = 71%, PPV = 52%, and NPV = 82% for proven GERD. Conclusions: The COuGH RefluX score has low sensitivity but adequate specificity for GERD diagnosis in Mexican patients with chronic laryngopharyngeal symptoms. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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11 pages, 1006 KB

Open AccessArticle

Cross-Cultural Adaptation and Validation of the Malayalam Version of the Vocal Tract Discomfort Scale

by Sunil Kumar Ravi, Srushti Shabnam, Saraswathi Thupakula, Vijaya Kumar Narne, Krishna Yerraguntla, Abdulaziz Almudhi, Irfana Madathodiyil, Feby Sajan and Kochette Ria Jacob

Diagnostics 2025, 15(3), 259; https://doi.org/10.3390/diagnostics15030259 - 23 Jan 2025

Cited by 1 | Viewed by 1571

Abstract

Background: Voice disorders significantly impact individuals’ physical, functional, and emotional well-being, necessitating comprehensive assessment tools. The Vocal Tract Discomfort Scale (VTDS) assesses the frequency and severity of vocal discomfort symptoms. Despite its global adaptations, no validated Malayalam version has existed. This study aimed to adapt and validate the VTDS for Malayalam speakers (VTDS-M). Method: The study was conducted in two phases: Phase I involved translation and cultural adaptation of VTDS into Malayalam, followed by content validation by native-speaking speech language pathologists; Phase II involved validation of VTDS-M on 150 professional voice users, categorized into normophonic (n = 105) and dysphonic (n = 45) groups based on otolaryngological and perceptual voice evaluations. Participants completed VTDS-M and VHI-M (Voice Handicap Index—Malayalam). Results: The results showed strong internal consistency (Cronbach’s α = 0.827 for frequency, 0.813 for severity). Significant differences were observed between groups for VTDS-M subscales and total scores, confirming its discriminatory capability. ROC analysis established a cut-off score of 11.5, with an AROC of 0.749, 64.4% sensitivity, and 79.0% specificity. Also, VTDS-M correlated positively with VHI-M, especially the physical and emotional subscales. Conclusions: VTDS-M demonstrated reliable psychometric properties and diagnostic accuracy, making it a valuable tool for assessing vocal discomfort in Malayalam-speaking populations specifically among the professional voice users. Future studies should explore its applicability to non-professional voice users with varied severity levels of dysphonia. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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13 pages, 2449 KB

Open AccessEditor’s ChoiceArticle

Incidence of Carotid Blowout Syndrome in Patients with Head and Neck Cancer after Radiation Therapy: A Cohort Study

by Jian-Lin Jiang, Joseph Tung-Chieh Chang, Chih-Hua Yeh, Ting-Yu Chang, Bing-Shen Huang, Pi-Shan Sung, Chien-Yu Lin, Kang-Hsing Fan, Yi-Chia Wei and Chi-Hung Liu

Diagnostics 2024, 14(12), 1222; https://doi.org/10.3390/diagnostics14121222 - 9 Jun 2024

Cited by 3 | Viewed by 3747

Abstract

Carotid blowout syndrome (CBS) is a rare yet life-threatening complication that occurs after radiation therapy (RT). This study aimed to determine the incidence of CBS in patients with head and neck cancer (HNC) undergoing contemporary RT and to explore potential discrepancies in the risk of CBS between nasopharyngeal cancer (NPC) and non-NPC patients. A total of 1084 patients with HNC who underwent RT between 2013 and 2023 were included in the study. All patients were under regular follow-ups at the radio-oncology department, and underwent annual contrast-enhanced computed tomography and/or magnetic resonance imaging for cancer recurrence surveillance. Experienced neuroradiologists and vascular neurologists reviewed the recruited patients’ images. Patients were further referred to the neurology department for radiation vasculopathy evaluation. The primary outcome of this study was CBS. Patients were categorized into NPC and non-NPC groups and survival analysis was employed to compare the CBS risk between the two groups. A review of the literature on CBS incidence was also conducted. Among the enrolled patients, the incidence of CBS in the HNC, NPC, and non-NPC groups was 0.8%, 0.9%, and 0.7%, respectively. Kaplan–Meier analysis revealed no significant difference between the NPC and non-NPC groups (p = 0.34). Combining the findings for our cohort with those of previous studies revealed that the cumulative incidence of CBS in patients with HNC is 5% (95% CI = 3–7%) after both surgery and RT, 4% (95% CI = 2–6%) after surgery alone, and 5% (95% CI = 3–7%) after RT alone. Our findings indicate a low incidence of CBS in patients with HNC undergoing contemporary RT. Patients with NPC may have a CBS risk close to that of non-NPC patients. However, the low incidence of CBS could be a potentially cause of selection bias and underestimation bias. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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Review

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26 pages, 976 KB

Open AccessReview

From Radical Resection to Precision Surgery: Integrating Diagnostic Biomarkers, Radiomics-Based Predictive Models, and Perioperative Systemic Therapy in Head and Neck Oncology

by Luiz P. Kowalski, Carol R. Bradford, Jonathan J. Beitler, Juan Pablo Rodrigo, Orlando Guntinas-Lichius, Petra Ambrosch, Arlene A. Forastiere, Karthik N. Rao, Marc Hamoir, Nabil F. Saba, Alvaro Sanabria, Primoz Strojan, Kevin Thomas Robbins and Alfio Ferlito

Diagnostics 2026, 16(1), 49; https://doi.org/10.3390/diagnostics16010049 - 23 Dec 2025

Viewed by 796

Abstract

Head and neck cancer surgery has evolved from radical organ-sacrificing procedures to function-preserving approaches integrated within multidisciplinary frameworks. This comprehensive literature review, concentrating on studies from the past five years while incorporating relevant publications from the last three decades and landmark historical papers, examines the evolving role of surgery emphasizing diagnostic methodologies including comprehensive genomic profiling, validated imaging biomarkers, and their clinical integration for treatment selection and response prediction. Modern surgical practice demonstrates a paradigm shift toward precision medicine through validated diagnostic technologies. Comprehensive genomic profiling identifies clinically actionable alterations in over 90% of head and neck squamous cell carcinomas, with tumor mutational burden serving as a validated predictive biomarker for immunotherapy response. Programmed death-ligand 1 (PD-L1) combined positive score functions as a validated diagnostic biomarker for immunotherapy efficacy, demonstrating significant clinical benefit in biomarker-selected populations. Radiomics-based predictive models utilizing machine learning algorithms achieve diagnostic accuracies exceeding 85% for treatment response prediction when validated across independent cohorts. Quantitative ultrasound spectroscopy combined with magnetic resonance imaging radiomics demonstrates high sensitivity and specificity for radiation response prediction. Habitat imaging techniques characterizing tumor microenvironmental heterogeneity predict pathologic complete response to neoadjuvant chemoimmunotherapy with area under the curve values approaching 0.90 in validation studies. Integration of these diagnostic methodologies enables response-adaptive treatment strategies, with neoadjuvant chemotherapy facilitating mandibular preservation and adjuvant therapy omission in over half of human papillomavirus (HPV)-associated cases following surgical downstaging. Clinical validation of these diagnostic platforms enables accurate treatment response prediction and informed surgical decision-making, though standardization across institutions and demonstration of survival benefits through prospective trials remain essential for broader implementation. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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Other

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14 pages, 1446 KB

Open AccessSystematic Review

Biomarkers for Predicting Malignant Transformation of Premalignant Lesions of the Larynx: A Systematic Review

by Juan P. Rodrigo, Reydson Alcides de Lima-Souza, Fernando López, Göran Stenman, Abbas Agaymy, Miquel Quer, Vinidh Paleri, Ilmo Leivo, Alfons Nadal, Nina Zidar, Fernanda V. Mariano, Henrik Hellquist, Nina Gale and Alfio Ferlito

Diagnostics 2026, 16(2), 236; https://doi.org/10.3390/diagnostics16020236 - 12 Jan 2026

Viewed by 185

Abstract

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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28 pages, 765 KB

Open AccessSystematic Review

Radiomic-Based Machine Learning Classifiers for HPV Status Prediction in Oropharyngeal Cancer: A Systematic Review and Meta-Analysis

by Anna Luíza Damaceno Araújo, Luiz Paulo Kowalski, Alan Roger Santos-Silva, Brendo Vinícius Rodrigues Louredo, Cristina Saldivia-Siracusa, Otávio Augusto A. M. de Melo, Deivid Cabral, Andrés Coca-Pelaz, Orlando Guntinas-Lichius, Remco de Bree, Pawel Golusinski, Karthik N. Rao, Robert P. Takes, Nabil F. Saba and Alfio Ferlito

Diagnostics 2026, 16(1), 68; https://doi.org/10.3390/diagnostics16010068 - 24 Dec 2025

Viewed by 503

Abstract

Background: The aim of the present systematic review (SR) is to compile evidence regarding the use of radiomic-based machine learning (ML) models for predicting human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) patients and to assess their reliability, methodological frameworks, and clinical applicability. The SR was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD42025640065). Methods: Using the PICOS framework, the review question was defined as follows: “Can radiomic-based ML models accurately predict HPV status in OPSCC?” Electronic databases (Cochrane, Embase, IEEE Xplore, BVS, PubMed, Scopus, Web of Science) and gray literature (arXiv, Google Scholar and ProQuest) were searched. Retrospective cohort studies assessing radiomics for HPV prediction were included. Risk of bias (RoB) was evaluated using Prediction model Risk Of Bias ASsessment Tool (PROBAST), and data were synthesized based on imaging modality, architecture type/learning modalities, and the presence of external validation. Meta-analysis was performed for externally validated models using MetaBayesDTA and RStudio. Results: Twenty-four studies including 8627 patients were analyzed. Imaging modalities included computed tomography (CT), magnetic resonance imaging (MRI), contrast-enhanced computed tomography (CE-CT), and ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET). Logistic regression, random forest, eXtreme Gradient Boosting (XGBoost), and convolutional neural networks (CNNs) were commonly used. Most datasets were imbalanced with a predominance of HPV+ cases. Only eight studies reported external validation results. AUROC values ranged between 0.59 and 0.87 in the internal validation and between 0.48 and 0.91 in the external validation results. RoB was high in most studies, mainly due to reliance on p16-only HPV testing, insufficient events, or inadequate handling of class imbalance. Deep Learning (DL) models achieved moderate performance with considerable heterogeneity (sensitivity: 0.61; specificity: 0.65). In contrast, traditional models provided higher, more consistent performance (sensitivity: 0.72; specificity: 0.77). Conclusions: Radiomic-based ML models show potential for HPV status prediction in OPSCC, but methodological heterogeneity and a high RoB limit current clinical applicability. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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6 pages, 1510 KB

Open AccessCase Report

The Thyrohyoid Syndrome: Promoting Awareness with a Case Report and Systematic Review of the Literature

by Raphael Jeker, Linda März and Lukas Horvath

Diagnostics 2024, 14(12), 1227; https://doi.org/10.3390/diagnostics14121227 - 12 Jun 2024

Viewed by 4253

Abstract

Objective: Neck pain is commonly referred to an ENT specialist and can be caused by the little-known inflammatory condition of the lateral thyrohyoid ligament. The pathophysiology of this condition is believed to be inflammation subsequent to over-exertion or cervical trauma. Typically, patients present with chronic unilateral neck pain. Elicitation of localized tenderness over the axis of the lateral thyrohyoid ligament on palpation is a key finding for its diagnosis. We present an unusual case with an acute course and subcutaneous inflammation and discuss its management in an effort to raise awareness for this often-misdiagnosed syndrome. Methods: A systematic literature research on PubMed was performed selecting patients with a definitive diagnosis of thyrohyoid syndrome or lateral thyrohyoid ligament syndrome. Results: We collected 54 cases from three studies. This condition is an important differential diagnosis for acute or chronic antero-lateral or unilateral neck pain. Conclusion: No specific radiological findings are defined and a CT scan is therefore not necessary for its diagnosis, but ultrasound is a useful tool to primarily assess any neck lesion. Once the diagnosis is made, a local infiltration of steroids is the most sustainable treatment option and relapse prevention. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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