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Diagnostics
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Head and Neck Cancers: Diagnosis and Management
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Head and Neck Cancers: Diagnosis and Management

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 11294

Special Issue Editor

Dr. Cristiana Lo Nigro

E-Mail Website
Guest Editor
Laboratori Centrali, EO Ospedali Galliera, 16128 Genova, Italy
Interests: translational oncology; cancer genetics; epigenetics; biomarkers; head and neck cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Head and neck cancer (HNC) management is incredibly challenging, and despite innovation in radiation oncology and immunotherapy introduction in the metastatic setting, the prognosis in the recurrent metastatic HNC is dismal.

The current standard treatment for locally advanced HNC has remained unchanged for 20 years. A multidisciplinary network and the expertise of each specialist affect outcome in such patients.

A proper classification and diagnosis of HNC and the selection of adequate biomarkers, both predictive and prognostic, might change the future of HNC management, which at the moment is dated, not personalized, and based on agnostic approaches.

Dr. Cristiana Lo Nigro
Guest Editor

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Keywords

  • HNC
  • biomarkers
  • immunotherapy
  • combination approaches

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Published Papers (6 papers)

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Research

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19 pages, 6016 KiB  
Article
Clinical, Epidemiological, Morphological, and Immunohistochemical Aspects of Nasopharyngeal Carcinoma—4-Year Retrospective Study in the Western Part of Romania
by Maria Alina Marin, Raluca-Maria Closca, Aurel Marin, Marina Rakitovan, Adrian Nicoara, Marioara Poenaru, Marius Militaru and Flavia Baderca
Diagnostics 2024, 14(7), 722; https://doi.org/10.3390/diagnostics14070722 - 29 Mar 2024
Cited by 2 | Viewed by 1671
Abstract
Nasopharyngeal carcinoma is one of the most common malignant tumors in the head and neck region. The carcinogenesis is a complex process stimulated by many factors. Although the etiological factors and pathogenic mechanisms are not elucidated, the genetic susceptibility, environmental factors, and association [...] Read more.
Nasopharyngeal carcinoma is one of the most common malignant tumors in the head and neck region. The carcinogenesis is a complex process stimulated by many factors. Although the etiological factors and pathogenic mechanisms are not elucidated, the genetic susceptibility, environmental factors, and association with latent infection with Epstein–Barr Virus play an important role. The aim of this study was to present the main clinical and epidemiological data, as well as the morphological aspects and the immunohistochemical profile, of patients with nasopharyngeal carcinoma diagnosed in western Romania. The study was retrospective and included 36 nasopharyngeal carcinomas. The histopathological diagnosis was completed using immunohistochemical reactions for the following antibodies: p63, p53 and p16 protein, cytokeratins (CK) AE1/AE3, CK5, CK7, CK20 and 34βE12, epithelial membrane antigen (EMA), Epstein–Barr virus (EBV), leukocyte common antigen (LCA), CD20, CD4, CD8, CD68, CD117, and CD1a. The squamous malignant component of nasopharyngeal carcinoma presented with positivity for cytokeratins AE1/AE3, CK5, 34βE12, and p63. Undifferentiated nasopharyngeal carcinoma was positive for EMA in 67% of cases, and 28% of cases showed an immunoreaction for CD117 in the malignant epithelial component. Also, the p53 protein was positive in all the cases. One case of undifferentiated nasopharyngeal carcinoma was p16-positive, and two cases were positive for EBV. A peri- and intratumor cellular infiltrate rich in lymphocytes, with a predominance of CD20-positive B lymphocytes, interspersed with T lymphocytes, was observed. The T cells were CD4- and CD8-positive, predominantly intratumoral, and the CD4:CD8 ratio was 1:1 for 75% of the undifferentiated subtype and 89% for differentiated non-keratinized squamous cell carcinoma. All subtypes of nasopharyngeal carcinoma presented with an inflammatory infiltrate with numerous plasma cells, eosinophils, and dendritic cells, presenting as antigen CD1a- and CD68-positive, as well as in CD117-positive mast cells. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis and Management)
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9 pages, 12429 KiB  
Article
Concordance between Clinical and Pathological T and N Stages in Polish Patients with Head and Neck Cancers
by Aldona Chloupek, Joanna Kania and Dariusz Jurkiewicz
Diagnostics 2023, 13(13), 2202; https://doi.org/10.3390/diagnostics13132202 - 28 Jun 2023
Cited by 1 | Viewed by 1999
Abstract
Background: The TNM (tumor, node, metastasis) staging system is important for the successful treatment of head and neck cancers (HNCs). This study aimed to evaluate the concordance between clinical and pathological T and N stages in patients with HNCs in Poland. Methods: In [...] Read more.
Background: The TNM (tumor, node, metastasis) staging system is important for the successful treatment of head and neck cancers (HNCs). This study aimed to evaluate the concordance between clinical and pathological T and N stages in patients with HNCs in Poland. Methods: In this single-center retrospective study, clinical and pathological TNM staging data on 203 patients undergoing surgical treatment for HNC between 2011 and 2018 were collected and compared. The study group was classified as underdiagnosed, overdiagnosed, or correctly diagnosed with HNC based on pathological TNM staging. The concordance between clinical and pathological staging was evaluated using the kappa coefficient. Results: Clinical and pathological TNM staging showed concordance in 59.9% of patients for primary tumor (T) and in 79.3% of patients for lymph node (N) classifications. Moderate agreement between the clinical and pathological stages was shown for stage T, while substantial agreement was revealed for stage N. The size and extent of the tumor were underestimated or overestimated in 73 of the 182 patients (40.1%), while lymph node involvement was downstaged in 11 of the 53 patients (20.7%). Conclusions: The disparities between clinical and pathological staging of HNC demonstrate the need for standardization in physical and pathological examinations, as well as radiographic imaging. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis and Management)
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16 pages, 2268 KiB  
Article
Utility of CK8, CK10, CK13, and CK17 in Differential Diagnostics of Benign Lesions, Laryngeal Dysplasia, and Laryngeal Squamous Cell Carcinoma
by Novica Boricic, Ivan Boricic, Ivan Soldatovic, Jovica Milovanovic, Aleksandar Trivic and Tatjana Terzic
Diagnostics 2022, 12(12), 3203; https://doi.org/10.3390/diagnostics12123203 - 16 Dec 2022
Cited by 3 | Viewed by 1787
Abstract
There are no reliable immunohistochemical markers for diagnosing laryngeal squamous cell carcinoma (SCC) or diagnosing and grading laryngeal dysplasia. We aimed to evaluate the diagnostic utility of CK8, CK10, CK13, and CK17 in benign laryngeal lesions, laryngeal dysplasia, and laryngeal SCC. This retrospective [...] Read more.
There are no reliable immunohistochemical markers for diagnosing laryngeal squamous cell carcinoma (SCC) or diagnosing and grading laryngeal dysplasia. We aimed to evaluate the diagnostic utility of CK8, CK10, CK13, and CK17 in benign laryngeal lesions, laryngeal dysplasia, and laryngeal SCC. This retrospective study included 151 patients diagnosed with laryngeal papilloma, laryngeal polyps, laryngeal dysplasia, and laryngeal SCC who underwent surgical treatment between 2010 and 2020. Immunohistochemistry (IHC) was carried out using specific monoclonal antibodies against CK8, CK10, CK13, and CK17. Two experienced pathologists performed semi-quantitative scoring of IHC positivity. The diagnostic significance of the markers was analyzed. CK13 showed a sensitivity of 100% and a specificity of 82.5% for distinguishing between laryngeal SCC and laryngeal dysplasia and benign lesions. CK17 showed a sensitivity of 78.3% and specificity of 57.1% for the detection of laryngeal SCC vs. laryngeal dysplasia. CK10 showed a sensitivity of 80.0% for discriminating between low-grade and high-grade dysplasia, and a specificity of 61.1%. Loss of CK13 expression is a reliable diagnostic tool for diagnosing laryngeal lesions with malignant potential and determining resection lines. In lesions with diminished CK13 expression, CK17 could be used as an auxiliary immunohistochemical marker in diagnosing laryngeal SCC. In CK13-negative and CK17-positive lesions, CK10 positivity could be used to determine low-grade dysplasia. CK8 is not a useful IHC marker in differentiating between benign laryngeal lesions, laryngeal dysplasia, and laryngeal SCC. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis and Management)
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Review

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12 pages, 1119 KiB  
Review
The Role of Cytokinome in the HNSCC Tumor Microenvironment: A Narrative Review and Our Experience
by Nerina Denaro, Cinzia Solinas, Ornella Garrone, Carolina Cauchi, Fiorella Ruatta, Demi Wekking, Andrea Abbona, Matteo Paccagnella, Marco Carlo Merlano and Cristiana Lo Nigro
Diagnostics 2022, 12(11), 2880; https://doi.org/10.3390/diagnostics12112880 - 21 Nov 2022
Cited by 4 | Viewed by 2267
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. In locally advanced (LA) HNSCC, a multidisciplinary approach consisting of surgery followed by chemoradiation (CRT) or definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. In locally advanced (LA) HNSCC, a multidisciplinary approach consisting of surgery followed by chemoradiation (CRT) or definitive CRT is the mainstay of treatment. In recurrent metastatic (R/M), HNSCC immune checkpoint inhibitors (ICIs) with or without chemotherapy represent the new first-line option. However, cancer will recur in about two out of five patients with LA HNSCC. If progression occurs within six months from platin-radiotherapy treatment, anti-programmed cell death-1 (PD-1) may be prescribed. Otherwise, immunotherapy with or without chemotherapy might be considered if PD-L1 is expressed. Despite several improvements in the outcome of patients with R/M HNSCC, overall survival (OS) remains dismal, equaling a median of 14 months. In-depth knowledge of the tumor microenvironment (TME) would be required to change the course of this complex disease. In recent years, many predictive and prognostic biomarkers have been studied in the HNSCC TME, but none of them alone can select the best candidates for response to ICIs or targeted therapy (e.g., Cetuximab). The presence of cytokines indicates an immune response that might occur, among other things, after tumor antigen recognition, viral and bacterial infection, and physic damage. An immune response against HNSCC results in the production of some cytokines that induce a pro-inflammatory response and attract cells, such as neutrophils, macrophages, and T cell effectors, to enhance the innate and adaptive anti-tumor response. We revised the role of a group of cytokines as biomarkers for treatment response in HNSCC. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis and Management)
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Other

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15 pages, 5663 KiB  
Case Report
Unpredictable Metastasis in the Head and Neck Region: A Diagnostic Immunohistochemical Challenge
by Raluca-Maria Closca, Adrian Nicoara, Marina Rakitovan, Ion Cristian Mot and Flavia Baderca
Diagnostics 2023, 13(23), 3513; https://doi.org/10.3390/diagnostics13233513 - 23 Nov 2023
Viewed by 1044
Abstract
Metastatic disease is a complex and sequential process that involves the migration of tumor cells from the primary site to distant areas. This metastatic pathway is not always predictable. Therefore, this paper presents three rare cases of unusual metastases, due to their primary [...] Read more.
Metastatic disease is a complex and sequential process that involves the migration of tumor cells from the primary site to distant areas. This metastatic pathway is not always predictable. Therefore, this paper presents three rare cases of unusual metastases, due to their primary site: two metastases of a clear cell renal cell carcinoma, one gingival, and one nasal, as well as a mandibular metastasis of a hepatocellular carcinoma. In all cases, an incisional biopsy was performed in order to find out the diagnosis. After microscopical examination of morphological Hematoxylin and Eosin-stained slides, for all cases, immunohistochemical reactions were performed to support the primary tumor site. Two cases had a previous histopathological diagnosis of a primary tumor, while for the third case, the metastatic lesion represented the first manifestation of the neoplastic disease, with an unfavorable prognosis. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis and Management)
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17 pages, 3628 KiB  
Systematic Review
Perineural Invasion Is a Significant Prognostic Factor in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
by Nada Binmadi, Maha Alsharif, Soulafa Almazrooa, Suad Aljohani, Sara Akeel, Samira Osailan, Muhammad Shahzad, Wael Elias and Yasmin Mair
Diagnostics 2023, 13(21), 3339; https://doi.org/10.3390/diagnostics13213339 - 30 Oct 2023
Cited by 5 | Viewed by 1840
Abstract
(1) Objectives: This systematic review and meta-analysis aimed to summarize current evidence regarding the prognostic role of perineural invasion (PNI) in patients with oral squamous cell carcinoma (OSCC). (2) Methods: We searched Cochrane Central, ProQuest, PubMed, Scopus, Science Direct, and Web of Science, [...] Read more.
(1) Objectives: This systematic review and meta-analysis aimed to summarize current evidence regarding the prognostic role of perineural invasion (PNI) in patients with oral squamous cell carcinoma (OSCC). (2) Methods: We searched Cochrane Central, ProQuest, PubMed, Scopus, Science Direct, and Web of Science, using relevant keywords to identify eligible articles. Two independent reviewers conducted two-stage screening, data extraction, and quality assessment. The risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) criteria. All analyses were performed using comprehensive meta-analysis (CMA; version 3.3.070) software. (3) Results: The study included 101 published articles encompassing 26,062 patients. The pooled analyses showed that PNI was associated with significantly worse overall survival (OS; HR = 1.45, 95% CI: 1.32–1.58; p < 0.001), worse disease-specific survival (DSS; HR = 1.87, 95% CI: 1.65–2.12; p < 0.001), and worse disease-free survival (DFS; HR = 1.87, 95% CI: 1.65–2.12; p < 0.001). Similarly, both local recurrence-free survival (LRFS) and regional recurrence-free survival (RRFS) were worse in patients with PNI (HR = 2.31, 95% CI: 1.72–3.10, p < 0.001; and HR = 2.04, 95% CI: 1.51–2.74, p < 0.001), respectively. The random-effect estimate of three studies demonstrated that the presence of PNI was associated with worse failure-free survival (FFS; HR = 2.59, 95% CI: 1.12–5.98, p < 0.001). (4) Conclusions: The current evidence suggests that PNI can be used as an independent predictor of the prognosis for patients with OSCC. The presence of PNI was associated with worse OS, DFS, DSS, FFS, and with recurrence. Asian patients and patients with extra-tumoral or peripheral PNI invasion were associated with worse prognosis. Full article
(This article belongs to the Special Issue Head and Neck Cancers: Diagnosis and Management)
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