Cancers

Research

18 pages, 1897 KiB

Open AccessArticle

Unsupervised Hierarchical Clustering of Head and Neck Cancer Patients by Pre-Treatment Plasma Metabolomics Creates Prognostic Metabolic Subtypes

by Ronald C. Eldridge, Zhaohui S. Qin, Nabil F. Saba, Madelyn C. Houser, D. Neil Hayes, Andrew H. Miller, Deborah W. Bruner, Dean P. Jones and Canhua Xiao

Cancers 2023, 15(12), 3184; https://doi.org/10.3390/cancers15123184 - 14 Jun 2023

Cited by 1 | Viewed by 2303

Abstract

There is growing evidence that the metabolism is deeply intertwined with head and neck squamous cell carcinoma (HNSCC) progression and survival but little is known about circulating metabolite patterns and their clinical potential. We performed unsupervised hierarchical clustering of 209 HNSCC patients via [...] Read more.

There is growing evidence that the metabolism is deeply intertwined with head and neck squamous cell carcinoma (HNSCC) progression and survival but little is known about circulating metabolite patterns and their clinical potential. We performed unsupervised hierarchical clustering of 209 HNSCC patients via pre-treatment plasma metabolomics to identify metabolic subtypes. We annotated the subtypes via pathway enrichment analysis and investigated their association with overall and progression-free survival. We stratified the survival analyses by smoking history. High-resolution metabolomics extracted 186 laboratory-confirmed metabolites. The optimal model created two patient clusters, of subtypes A and B, corresponding to 41% and 59% of the study population, respectively. Fatty acid biosynthesis, acetyl-CoA transport, arginine and proline, as well as the galactose metabolism pathways differentiated the subtypes. Relative to subtype B, subtype A patients experienced significantly worse overall and progression-free survival but only among ever-smokers. The estimated three-year overall survival was 61% for subtype A and 86% for subtype B; log-rank p = 0.001. The association with survival was independent of HPV status and other HNSCC risk factors (adjusted hazard ratio = 3.58, 95% CI: 1.46, 8.78). Our findings suggest that a non-invasive metabolomic biomarker would add crucial information to clinical risk stratification and raise translational research questions about testing such a biomarker in clinical trials. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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20 pages, 5259 KiB

Open AccessArticle

Integrative Analysis of N6-Methyladenosine-Related Enhancer RNAs Identifies Distinct Prognosis and Tumor Immune Micro-Environment Patterns in Head and Neck Squamous Cell Carcinoma

by Hongshi Cai, Jianfeng Liang, Yaoqi Jiang, Rukeng Tan, Chen Hou and Jinsong Hou

Cancers 2022, 14(19), 4657; https://doi.org/10.3390/cancers14194657 - 25 Sep 2022

Cited by 4 | Viewed by 2114

Abstract

At present, the prognostic value of N6-methyladenosine (m6A)-related enhancer RNAs (eRNAs) for head and neck squamous cell carcinoma (HNSCC) still remains unclear. Our study aims to explore the prognostic value of m6A-related eRNAs in HNSCC patients and their potential significance in immune infiltration [...] Read more.

At present, the prognostic value of N6-methyladenosine (m6A)-related enhancer RNAs (eRNAs) for head and neck squamous cell carcinoma (HNSCC) still remains unclear. Our study aims to explore the prognostic value of m6A-related eRNAs in HNSCC patients and their potential significance in immune infiltration and immunotherapy. We constructed a 5 m6A-related eRNAs risk model from The Cancer Genome Atlas (TCGA) HNSCC dataset, using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the SRAMP website and in vitro experiments, it was verified that these 5 m6A-related eRNAs had m6A sites, the expression of which was regulated by corresponding m6A regulators. Moreover, we constructed a nomogram base on 5 m⁶A-related eRNAs and confirmed the consistency and robustness of an internal TCGA testing set. Further analysis found that the risk score was positively associated with low overall survival (OS), tumor cell metastasis, metabolic reprogramming, low immune surveillance, lower expression of immune-related genes, and higher expression of targeted genes. Finally, we verified that silencing MIR4435-2HG inhibited HNSCC cell migration and invasion. This study contributes to the understanding of the characteristics of m6A-related eRNAs in HNSCC and provides a reference for effective immunotherapy and targeted therapy. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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13 pages, 1888 KiB

Open AccessArticle

Human Leucocyte Antigens as Prognostic Markers in Head and Neck Squamous Cell Carcinoma

by Gerhard Dyckhoff, Christel Herold-Mende, Sabine Scherer, Peter K. Plinkert and Rolf Warta

Cancers 2022, 14(15), 3828; https://doi.org/10.3390/cancers14153828 - 7 Aug 2022

Cited by 7 | Viewed by 1986

Abstract

Background: The induction and regulation of immune responses depend on human leucocyte antigen (HLA) molecules that present peptides derived from mutated neoantigens or tumor-associated antigens to cytotoxic T cells. The natural variation of HLA molecules might differ between tumor patients and the normal [...] Read more.

Background: The induction and regulation of immune responses depend on human leucocyte antigen (HLA) molecules that present peptides derived from mutated neoantigens or tumor-associated antigens to cytotoxic T cells. The natural variation of HLA molecules might differ between tumor patients and the normal population. Thus, there might be associations between the frequencies of HLA alleles and the survival of tumor patients. Methods: This issue was studied in a cohort of 84 patients with head and neck squamous cell carcinomas (HNSCCs) of different localizations. The cohort was followed up for more than 10 years. HLA-A/B/C CTS-PCR-SSP typing at 1 field level from blood samples was performed, and the results were correlated with survival. Results: HLA-A*02 was the most prevalent allele in our cohort and was present in 51.1% of patients. The HLA-A*25 and HLA-C*06 alleles exhibited a significantly higher frequency in cancer patients than in the normal population of 174 blood and kidney donors (p = 0.02 and p = 0.01, respectively, Fisher’s exact test). For HLA-C*04, a negative impact on overall survival in univariate analysis (p = 0.045) and a negative, but statistically insignificant effect on survival toward poorer survival in multivariate analysis (HR: 1.82; 95% CI: 0.99–3.34, p = 0.053) were observed. In addition, HLA-A*02 was also beneficial for overall survival and progression-free survival in multivariate analysis (HR 0.54; 95% CI: 0.31–0.92; p = 0.023). Conclusion: HLA-A*02 allele expression might not only predict better survival but might also indicate superior tumor antigen presentation and, thus, help to select patients who could benefit from T-cell-dependent immunotherapies. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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15 pages, 1498 KiB

Open AccessArticle

Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions

by Verona E. Bergshoeff, Maschenka C. A. Balkenhol, Annick Haesevoets, Andrea Ruland, Michelene N. Chenault, Rik C. Nelissen, Carine J. Peutz, Ruud Clarijs, Jeroen A. W. M. Van der Laak, Robert P. Takes, Michiel W. Van den Brekel, Marie-Louise F. Van Velthuysen, Frans C. S. Ramaekers, Bernd Kremer and Ernst-Jan M. Speel

Cancers 2022, 14(13), 3260; https://doi.org/10.3390/cancers14133260 - 3 Jul 2022

Viewed by 1841

Abstract

Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions [...] Read more.

Background: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI. Methods: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/− 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%). Results: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%). Conclusions: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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18 pages, 1901 KiB

Open AccessArticle

Concordance, Correlation, and Clinical Impact of Standardized PD-L1 and TIL Scoring in SCCHN

by Stijn Jeroen De Keukeleire, Tijl Vermassen, Philippe Deron, Wouter Huvenne, Fréderic Duprez, David Creytens, Jo Van Dorpe, Liesbeth Ferdinande and Sylvie Rottey

Cancers 2022, 14(10), 2431; https://doi.org/10.3390/cancers14102431 - 14 May 2022

Cited by 10 | Viewed by 2464

Abstract

Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored [...] Read more.

Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored the concordance of PD-L1 combined positive score (CPS) and stromal TILs in different paired tissue sample types, while evaluating their internal relationship and prognostic impact. Methods: A total of 165 tissue blocks from 80 SCCHN patients were reviewed for TILs and PD-L1 CPS. Concordance between paired tissue samples was evaluated, and their association with several clinicopathological variables, overall survival (OS), and disease-free survival (DFS) was determined. Results: Biopsies and paired resection material were severely discordant in 39% and 34% of samples for CPS and TIL count, respectively, of which CPS was underscored in 27% of biopsies. In paired primary tumor–metastatic lesions, the disagreement was lower for CPS (19%) but not for TIL count (44%). PD-L1 CPS was correlated with prolonged OS when calculated from tissue acquirement, while extended OS and DFS were observed for high TIL density. Conclusion: Intertumoral and, especially, intratumoral heterogeneity were confounding factors when determining PD-L1 CPS and TIL count on paired tissue samples, indicating the increasing necessity of assessing both biomarkers on representative tissue material. Although TILs hold valuable prognostic information in SCCHN, the robustness of PD-L1 as a biomarker in SCCHN remains ambiguous. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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15 pages, 11700 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

HPRT1 Promotes Chemoresistance in Oral Squamous Cell Carcinoma via Activating MMP1/PI3K/Akt Signaling Pathway

by Tong Wu, Zan Jiao, Yixuan Li, Xuan Su, Fan Yao, Jin Peng, Weichao Chen and Ankui Yang

Cancers 2022, 14(4), 855; https://doi.org/10.3390/cancers14040855 - 9 Feb 2022

Cited by 28 | Viewed by 3462

Abstract

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene. However, recent reports have indicated that HPRT1 overexpression is associated with a poor prognosis in various types of cancers. Using The Cancer Genome Atlas (TCGA), HPRT1 was found to be [...] Read more.

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene. However, recent reports have indicated that HPRT1 overexpression is associated with a poor prognosis in various types of cancers. Using The Cancer Genome Atlas (TCGA), HPRT1 was found to be highly expressed in various cancer types, especially in head and neck squamous cell carcinoma (HNSCC). Therefore, we measured HPRT1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between HPRT1 expression and clinical pathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC), a common type of HNSCC. We built OSCC cells with stable knockdown and overexpression of HPRT1 to observe its influence on chemoresistance and malignancy in vitro and vivo. We found that highly expressed HPRT1 was associated with a poor prognosis and could promote resistance to cisplatin (CDDP) in OSCC cells in both in vitro and in vivo. An RNA sequence assay was carried out to explore the mechanism of function of HPRT1, we found that HPRT1 could positively regulate the expression of MMP1 and the activation of the PI3K/AKT pathway, to regulate the resistance to CDDP of OSCC. In conclusion, HPRT1 can no longer be simply believed to be a housekeeping gene. HPRT1 overexpression indicates a worse prognosis and can improve CDDP resistance for patients with OSCC by promoting the MMP1/PI3K/Akt axis. HPRT1 may be a potential prognostic biomarker and therapeutic target in OSCC. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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15 pages, 2008 KiB

Open AccessArticle

CDK7 Predicts Worse Outcome in Head and Neck Squamous-Cell Cancer

by Tobias Jagomast, Christian Idel, Luise Klapper, Patrick Kuppler, Anne Offermann, Eva Dreyer, Karl-Ludwig Bruchhage, Julika Ribbat-Idel and Sven Perner

Cancers 2022, 14(3), 492; https://doi.org/10.3390/cancers14030492 - 19 Jan 2022

Cited by 6 | Viewed by 2759

Abstract

HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities. pMED1 is phosphorylated by CDK7. Importantly, [...] Read more.

HNSCC is the sixth most common cancer worldwide and the prognosis is still poor. Here, we investigated the prognostic implications of CDK7 and pMED1. Both proteins affect transcription, and their expression is altered throughout different tumor entities. pMED1 is phosphorylated by CDK7. Importantly, CDK7 and MED1 have been ascribed prognostic implications by various studies. However, their prognostic value in head and neck squamous-cell cancer (HNSCC) remains elusive. We applied immunohistochemical staining of CDK7 and pMED1 on our large and clinically well-characterized HNSCC tissue cohort comprising 419 patients. Software-aided quantification of staining intensity was performed as a measure of protein expression. The following results were linked to the clinicopathological features of our cohort and correlated in different tissue types (primary tumor, lymph node metastasis, distant metastasis, recurrence). Upregulation CDK7 was associated with worse 5-year overall survival as well as disease-free survival in HNSCC while being independent of other known prognostic factors such as p16-status. Also, CDK7 expression was significantly elevated in immune cell infiltrated tumors. In HNSCC CDK7 might serve as a novel prognostic marker to indicate the prognosis of patients. Furthermore, in vitro studies proved the feasibility of CDK7 inhibition with attenuating effects on cell proliferation underlining its remarkable translational potential for future therapeutic regimes. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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Review

Jump to: Research, Other

19 pages, 1545 KiB

Open AccessReview

Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma

by Anna Brandt, Benjamin Thiele, Christoph Schultheiß, Eveline Daetwyler and Mascha Binder

Cancers 2023, 15(7), 2051; https://doi.org/10.3390/cancers15072051 - 30 Mar 2023

Cited by 3 | Viewed by 5268

Abstract

Tumors shed cell-free DNA (cfDNA) into the plasma. “Liquid biopsies” are a diagnostic test to analyze cfDNA in order to detect minimal residual cancer, profile the genomic tumor landscape, and monitor cancers non-invasively over time. This technique may be useful in patients with [...] Read more.

Tumors shed cell-free DNA (cfDNA) into the plasma. “Liquid biopsies” are a diagnostic test to analyze cfDNA in order to detect minimal residual cancer, profile the genomic tumor landscape, and monitor cancers non-invasively over time. This technique may be useful in patients with head and neck squamous cell carcinoma (HNSCC) due to genetic tumor heterogeneity and limitations in imaging sensitivity. However, there are technical challenges that need to be overcome for the widespread use of liquid biopsy in the clinical management of these patients. In this review, we discuss our current understanding of HNSCC genetics and the role of cfDNA genomic analyses as an emerging precision diagnostic tool. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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21 pages, 2489 KiB

Open AccessReview

Extracellular Vesicles as Biomarkers in Head and Neck Squamous Cell Carcinoma: From Diagnosis to Disease-Free Survival

by Bojie Chen, Leanne Lee Leung, Xinyu Qu and Jason Ying-Kuen Chan

Cancers 2023, 15(6), 1826; https://doi.org/10.3390/cancers15061826 - 17 Mar 2023

Cited by 5 | Viewed by 2621

Abstract

Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many [...] Read more.

Head and neck squamous cell carcinomas (HNSCCs) arising from different anatomical sites present with different incidences and characteristics, which requires a personalized treatment strategy. Despite the extensive research that has conducted on this malignancy, HNSCC still has a poor overall survival rate. Many attempts have been made to improve the outcomes, but one of the bottlenecks is thought to be the lack of an effective biomarker with high sensitivity and specificity. Extracellular vesicles (EVs) are secreted by various cells and participate in a great number of intercellular communications. Based on liquid biopsy, EV detection in several biofluids, such as blood, saliva, and urine, has been applied to identify the existence and progression of a variety of cancers. In HNSCC, tumor-derived EVs exhibit many functionalities by transporting diverse cargoes, which highlights their importance in tumor screening, the determination of multidisciplinary therapy, prediction of prognosis, and evaluation of therapeutic effects. This review illustrates the classification and formation of EV subtypes, the cargoes conveyed by these vesicles, and their respective functions in HNSCC cancer biology, and discloses their potential as biomarkers during the whole process of tumor diagnosis, treatment, and follow-up. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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16 pages, 2275 KiB

Open AccessReview

Molecular Biomarkers of Malignant Transformation in Head and Neck Dysplasia

by Kushi Ranganath, Allen L. Feng, Ramon A. Franco, Mark A. Varvares, William C. Faquin, Matthew R. Naunheim and Srinivas Vinod Saladi

Cancers 2022, 14(22), 5581; https://doi.org/10.3390/cancers14225581 - 15 Nov 2022

Cited by 3 | Viewed by 2890

Abstract

Head and neck squamous cell carcinoma (HNSCC) and its treatments are associated with substantial morbidity, often resulting in cosmetic deformity and loss of physiologic functions including speech and swallowing. Despite advancements in treatment, 5-year survival rates for mucosal malignancies remain below 70%. Effective [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) and its treatments are associated with substantial morbidity, often resulting in cosmetic deformity and loss of physiologic functions including speech and swallowing. Despite advancements in treatment, 5-year survival rates for mucosal malignancies remain below 70%. Effective prevention of HNSCC demands an understanding of the molecular pathways of carcinogenesis. Specifically, defining features of pre-cancerous dysplastic lesions that indicate a better or worse prognosis is necessary to help identify patients who are likely to develop a carcinoma and allow a more aggressive approach to management. There remains a need for identification of biomarkers that can provide both early prognostic and predictive value in clinical decision-making by serving as both therapeutic targets as well as predictors of therapy response. Here, we comprehensively review the most frequently altered molecular biomarkers of malignant transformation in head and neck dysplasia. These markers are involved in a wide range of cellular processes in head and neck carcinogenesis, including extracellular matrix degradation, cell motility and invasion, cell–cell adhesion, solute transport, immortalization, metabolism, the cell cycle and apoptosis, transcription, and cell signaling. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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24 pages, 1337 KiB

Open AccessReview

Circulating Cell-Free DNA-Based Methylation Pattern in Saliva for Early Diagnosis of Head and Neck Cancer

by Natalia Birknerova, Veronika Mancikova, Evan David Paul, Jan Matyasovsky, Pavol Cekan, Vladimir Palicka and Helena Parova

Cancers 2022, 14(19), 4882; https://doi.org/10.3390/cancers14194882 - 6 Oct 2022

Cited by 12 | Viewed by 4708

Abstract

Head and neck cancer (HNC) remains one of the leading causes of mortality worldwide due to tumor diagnosis at a late stage, loco-regional aggression, and distant metastases. A standardized diagnostic procedure for HNC is a tissue biopsy that cannot faithfully portray the in-depth [...] Read more.

Head and neck cancer (HNC) remains one of the leading causes of mortality worldwide due to tumor diagnosis at a late stage, loco-regional aggression, and distant metastases. A standardized diagnostic procedure for HNC is a tissue biopsy that cannot faithfully portray the in-depth tumor dynamics. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for cancer detection and follow-up. A saliva-based liquid biopsy allows convenient, non-invasive, and painless collection of high volumes of this biofluid, with the possibility of repetitive sampling, all enabling real-time monitoring of the disease. No approved clinical test for HNC has yet been established. However, epigenetic changes in saliva circulating cell-free DNA (cfDNA) have the potential for a wide range of clinical applications. Therefore, the aim of this review is to present an overview of cfDNA-based methylation patterns in saliva for early detection of HNC, with particular attention to circulating tumor DNA (ctDNA). Due to advancements in isolation and detection technologies, as well as next- and third-generation sequencing, recent data suggest that salivary biomarkers may be successfully applied for early detection of HNC in the future, but large prospective clinical trials are still warranted. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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23 pages, 373 KiB

Open AccessReview

Liquid Biopsy in Head and Neck Cancer: Current Evidence and Future Perspective on Squamous Cell, Salivary Gland, Paranasal Sinus and Nasopharyngeal Cancers

by Santiago Cabezas-Camarero and Pedro Pérez-Segura

Cancers 2022, 14(12), 2858; https://doi.org/10.3390/cancers14122858 - 9 Jun 2022

Cited by 11 | Viewed by 3688

Abstract

Head and neck cancer (HNC) is currently the sixth most common solid malignancy, accounting for a 50% five-year mortality rate. In the past decade, substantial improvements in understanding its molecular biology have allowed for a growing development of new biomarkers. Among these, the [...] Read more.

Head and neck cancer (HNC) is currently the sixth most common solid malignancy, accounting for a 50% five-year mortality rate. In the past decade, substantial improvements in understanding its molecular biology have allowed for a growing development of new biomarkers. Among these, the field of liquid biopsy has seen a sustained growth in HNC, demonstrating the feasibility to detect different liquid biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTC), extracellular vesicles and microRNAs. Liquid biopsy has been studied in HPV-negative squamous cell carcinoma of the head and neck (SCCHN) but also in other subentities such as HPV-related SCCHN, EBV-positive nasopharyngeal cancer and oncogene-driven salivary gland cancers. However, future studies should be internally and externally validated, and ideally, clinical trials should incorporate the use of liquid biomarkers as endpoints in order to prospectively demonstrate their role in HNC. A thorough review of the current evidence on liquid biopsy in HNC as well as its prospects will be conducted. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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13 pages, 2343 KiB

Open AccessSystematic Review

Neutrophil to Lymphocyte Ratio in Oropharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

by Juan P. Rodrigo, Mario Sánchez-Canteli, Asterios Triantafyllou, Remco de Bree, Antti A. Mäkitie, Alessandro Franchi, Henrik Hellquist, Nabil F. Saba, Göran Stenman, Robert P. Takes, Cristina Valero, Nina Zidar and Alfio Ferlito

Cancers 2023, 15(3), 802; https://doi.org/10.3390/cancers15030802 - 28 Jan 2023

Cited by 12 | Viewed by 2868

Abstract

Neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in various cancers, including head and neck cancer. However, there is limited information on its role in oropharyngeal squamous cell carcinomas (OPSCC) according to HPV status. This prompted the present meta-analysis. Studies were selected when [...] Read more.

Neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in various cancers, including head and neck cancer. However, there is limited information on its role in oropharyngeal squamous cell carcinomas (OPSCC) according to HPV status. This prompted the present meta-analysis. Studies were selected when the prognostic value of NLR prior to treatment was evaluated in OPSCC patients, the cutoff value of NLR was available, and the prognostic value of NLR was evaluated by time-to-event survival analysis. A total of 14 out of 492 articles, including 7647 patients, were analyzed. The results showed a worse prognosis for the patients with a high NLR: The combined hazard ratios (HR) for overall survival (OS) in patients with an elevated NLR was 1.56 (95% confidence interval (CI) 1.21–2.02; p = 0.0006), for disease-free survival was 1.52 (95% CI 1.34–1.73; p < 0.00001), and for recurrence-free survival was 1.86 (95% CI 1.50–2.30; p < 0.00001). This worse prognosis of high NLR was exclusive of HPV-positive patients: HR for OS in the HPV-positive subgroup was 4.05 (95% CI 1.90–8.62 (p = 0.0003), and in the HPV-negative subgroup 0.92 (95% CI 0.47–1.80; p = 0.82). The prognosis of NLR was not influenced by treatment: The HR for OS for patients treated with radiotherapy/chemoradiotherapy (RT/CRT) was 1.48 (95% CI 1.09–2.01; p = 0.01), and for patients treated with surgery (±RT/CRT) was 1.72 (95% CI 1.08–2.72; p = 0.02). In conclusion, an elevated NLR relates to worse outcomes in patients with HPV-positive OPSCC. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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10 pages, 667 KiB

Open AccessPerspective

Insight into Classification and Risk Stratification of Head and Neck Squamous Cell Carcinoma in Era of Emerging Biomarkers with Focus on Histopathologic Parameters

by Antti A. Mäkitie, Abbas Agaimy and Alhadi Almangush

Cancers 2022, 14(22), 5514; https://doi.org/10.3390/cancers14225514 - 10 Nov 2022

Cited by 5 | Viewed by 3075

Abstract

Tumor-node-metastasis (TNM) staging system is the cornerstone for treatment planning of head and neck squamous cell carcinoma (HNSCC). Many prognostic biomarkers have been introduced as modifiers to further improve the TNM classification of HNSCC. Here, we provide an overview on the use of [...] Read more.

Tumor-node-metastasis (TNM) staging system is the cornerstone for treatment planning of head and neck squamous cell carcinoma (HNSCC). Many prognostic biomarkers have been introduced as modifiers to further improve the TNM classification of HNSCC. Here, we provide an overview on the use of the recent prognostic biomarkers, with a focus on histopathologic parameters, in improving the risk stratification of HNSCC and their application in the next generation of HNSCC staging systems. Full article

(This article belongs to the Special Issue The Biomarkers and Detection of Head and Neck Cancer)

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