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1
Rahman, Sadia, Sandra Kraljević Pavelić, and Elitza Markova-Car. "Circadian (De)regulation in Head and Neck Squamous Cell Carcinoma." International Journal of Molecular Sciences 20, no. 11 (May 30, 2019): 2662. http://dx.doi.org/10.3390/ijms20112662.
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Head and neck cancer encompass different malignancies that develop in and around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas (HNSCC) that arise in the flat squamous cells that makeup the thin layer of tissue on the surface of anatomical structures in the head and neck. Each year, HNSCC is diagnosed in more than 600,000 people worldwide, with about 50,000 new cases. HNSCC is considered extremely curable if detected early. But the problem remains in treatment of inoperable cases, residues or late stages. Circadian rhythm regulation has a big role in developing various carcinomas, and head and neck tumors are no exception. A number of studies have reported that alteration in clock gene expression is associated with several cancers, including HNSCC. Analyses on circadian clock genes and their association with HNSCC have shown that expression of PER1, PER2, PER3, CRY1, CRY2, CKIε, TIM, and BMAL1 are deregulated in HNSCC tissues. This review paper comprehensively presents data on deregulation of circadian genes in HNSCC and critically evaluates their potential diagnostics and prognostics role in this type of pathology.
2
Ragin, C. C. R., F. Modugno, and S. M. Gollin. "The Epidemiology and Risk Factors of Head and Neck Cancer: a Focus on Human Papillomavirus." Journal of Dental Research 86, no. 2 (February 2007): 104–14. http://dx.doi.org/10.1177/154405910708600202.
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Head and neck cancer was the eighth leading cause of cancer death worldwide in 2000. Although the incidence of head and neck squamous cell carcinoma (HNSCC) in the United States is relatively low, survival is poor and has not improved for several decades. While tobacco and alcohol are the primary risk factors for HNSCC development, epidemiological studies report a strong association with human papillomavirus (HPV) in a subset of HNSCC. More than 95% of cervical squamous cell carcinomas are linked to persistent HPV infection; evidence demonstrates that HPV is a necessary carcinogen. Not all HPV-positive HNSCC express the viral oncogenes ( E6 and E7), which suggests that HPV may function as a carcinogen in a smaller proportion of HNSCC. This review presents our current understanding of the relationship between HPV and HNSCC, and describes future research directions that may lead to a better understanding of the involvement of HPV in head and neck cancer.
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Meireles Da Costa, Nathalia, Fábio A. Mendes, Bruno Pontes, Luiz Eurico Nasciutti, Luis Felipe Ribeiro Pinto, and Antonio Palumbo Júnior. "Potential Therapeutic Significance of Laminin in Head and Neck Squamous Carcinomas." Cancers 13, no. 8 (April 15, 2021): 1890. http://dx.doi.org/10.3390/cancers13081890.
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Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors.
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Norouzian, Marzieh, and Sima Balouchi-Anaraki. "Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma: A Focus on Tumor-Infiltrating Lymphocytes." Asian Pacific Journal of Cancer Biology 4, no. 2 (August 1, 2019): 19–26. http://dx.doi.org/10.31557/apjcb.2019.4.1.15-22.
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For more progress in head and neck squamous cell carcinoma (HNSCC) immuno-oncology, further understanding of interactions between tumor and immune system as well as factors in the tumor microenvironment is required. HNSCC is seriously infiltrated by lymphocytes but is known to be highly immunosuppressive. The aim of this review is to highlight the complexity of tumor microenvironment and tumor- immune cells interaction in the HNSCC, in order to improve understanding of tumorigenesis and disease progression in HNSCC patient and to provide valuable information about prognostic markers. The main goal of this review is to discuss the role of the tumor infiltrating lymphocytes in tumor progression, their cross-talk with other components of the tumor microenvironment as well as their roles in carcinogenesis, metastasis process, treatment, and prognosis in head and neck squamous cell carcinomas.
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Lai, Sook Ling, May Leng Tan, Robert J. Hollows, Max Robinson, Maha Ibrahim, Sandra Margielewska, E. Kenneth Parkinson, et al. "Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1." Cancers 11, no. 11 (November 9, 2019): 1766. http://dx.doi.org/10.3390/cancers11111766.
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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.
6
Davidson, Beverly L., Scott M. Graham, Eric A. Goebel, Joseph Zabner, and Jeffrey A. Kern. "Adenovirus-Mediated Gene Therapy for Head and Neck Squamous Cell Carcinomas." Annals of Otology, Rhinology & Laryngology 105, no. 7 (July 1996): 562–67. http://dx.doi.org/10.1177/000348949610500713.
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Advanced head and neck squamous cell carcinomas (HNSCCs) have a poor prognosis despite aggressive multimodal therapy. The goal of our study was to test the feasibility of gene transduction as a novel therapy for head and neck cancer. Three human HNSCC cell lines were transduced in vitro with a replication-deficient recombinant adenovirus containing the lacZ marker gene (Ad2/CMVßgal). Gene transduction efficiency was dependent on multiplicity of infection, duration of exposure to the virus, and viral concentration. Next, the HEp-2 cell line was transduced with an adenoviral vector (Ad.RSV tk) containing the herpes simplex virus thymidine kinase (HSV tk) gene, which, when expressed, sensitizes transduced cells to ganciclovir (GCV). Subsequent administration of GCV resulted in complete rumor cell killing. These results suggest that adenovirus-mediated transfer of KSV tk and administration of GCV has potential as a new therapy for HNSCC.
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Chen, Huimin, Ke Hu, Ying Xie, Yucheng Qi, Wenjuan Li, Yaohui He, Shijie Fan, Wen Liu, and Chenghua Li. "CDK1 Promotes Epithelial–Mesenchymal Transition and Migration of Head and Neck Squamous Carcinoma Cells by Repressing ∆Np63α-Mediated Transcriptional Regulation." International Journal of Molecular Sciences 23, no. 13 (July 2, 2022): 7385. http://dx.doi.org/10.3390/ijms23137385.
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∆Np63α is a key transcription factor overexpressed in types of squamous cell carcinomas (SCCs), which represses epithelial–mesenchymal transition (EMT) and cell migration. In this study, we found that CDK1 phosphorylates ∆Np63α at the T123 site, impairing its affinity to the target promoters of its downstream genes and its regulation of them in turn. Database analysis revealed that CDK1 is overexpressed in head and neck squamous cell carcinomas (HNSCCs), especially the metastatic HNSCCs, and is negatively correlated with overall survival. We further found that CDK1 promotes the EMT and migration of HNSCC cells by inhibiting ∆Np63α. Altogether, our study identified CDK1 as a novel regulator of ΔNp63α, which can modulate EMT and cell migration in HNSCCs. Our findings will help to elucidate the migration mechanism of HNSCC cells.
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Porcheri, Cristina, and Thimios A. Mitsiadis. "New Scenarios in Pharmacological Treatments of Head and Neck Squamous Cell Carcinomas." Cancers 13, no. 21 (November 3, 2021): 5515. http://dx.doi.org/10.3390/cancers13215515.
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Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer with a lethal outcome in half of the diagnosed cases. Mostly, HNSCC develops in the oral cavity, and its development is associated with tobacco and areca nut/betel quid usage, alcohol consumption, and HPV infection. Oral squamous cell carcinoma, as other head and neck cancers, presents a high degree of intratumor heterogeneity, which makes their treatment difficult, and directly correlates with drug resistance. Since the classical treatments for HNSCC oftentimes do not resolve the clinical picture, there is great need for novel therapeutic approaches, models for drug testing, and new drug delivery systems.
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Bancu, Bancu, Richard Cowan, and Anshuman Chaturvedi. "PD-L1 TESTING AND IMMUNOTHERAPY SELECTION – EARLY LABORATORY EXPERIENCE AND ITS POTENTIAL ROLE IN HEAD AND NECK CANCER MANAGEMENT." Archive of Clinical Cases 8, no. 1 (March 31, 2021): 14–18. http://dx.doi.org/10.22551/2021.30.0801.10179.
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Anti-programmed cell death protein-1 (PD-1) therapy has been relatively recently approved in a defined context by NICE in adults in the management of recurrent and metastatic head and neck squamous cell carcinomas (HNSCC). In this context, companion diagnostic programmed cell death ligand-1 (PD-L1) testing, previously established at our center for lung and bladder tumors, was undertaken in a few head and neck cancer cases. The scope of this study was to audit the relevant PD-L1 data and integrate the findings in our current clinical practice, with a view to promote improved routine laboratory biomarkers in HNSCC. Histopathology reports documenting tumor type, PD-L1 result and type of clone/assay were included in this study. Over a 5-year period, PD-L1 testing was undertaken in 199 cancer cases, including 3 with head and neck squamous carcinoma with low focal positive staining. Immunotherapy treatment in HNSCC demonstrates a discreet but still significant improvement in the overall survival of PD-L1 positive subjects.
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Baba, Yuh, Masato Fujii, Yutaka Tokumaru, and Yasumasa Kato. "Present and Future of EGFR Inhibitors for Head and Neck Squamous Cell Cancer." Journal of Oncology 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/986725.
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Although EGFR is expressed at high levels in head and neck squamous cell carcinomas (HNSCCs) and mutations are extremely rare, monotherapy with EGFR inhibitors has shown limited success. The PI3kinase/Akt pathway is responsible for cellular survival, and inhibition of phosphatidylinositol (PI) synthesis has antiproliferative, anti-invasive, and antiangiogenesis effects on HNSCC. Molecular crosstalk has been observed between EGFR and IGF1R signaling through the PI3kinase/Akt pathway in HNSCC, as has molecular crosstalk between the NFκB and STAT3 signaling pathways. Therefore, the combination of an EGFR antagonist with an agent that inhibits the activation of both Akt and NFκB may overcome resistance to EGFR antagonists in HNSCC.
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Fang, Han, Yakui Mou, Wenbin Zhang, Hua Bao, Min Wu, Xiaoxi Chen, Xuxiaochen Wu, Ruowei Yang, Dongqin Zhu, and Xicheng Song. "Multi-dimensional cell-free DNA-based liquid biopsy for sensitive detection of head and neck squamous cell carcinomas." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): e18054-e18054. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e18054.
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e18054 Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. The mortality from HNSCC is closely linked to stage. However, the majority of HNSCC patients were diagnosed at an advanced stage. Therefore, a non-invasive assay for the early detection of HNSCCs is highly desirable for reducing the associated mortality. Methods: We collected a study cohort of 281 participants including 140 pathologically confirmed with head and neck squamous cell carcinomas (HNSCCs) and 141 with non-cancerous conditions. A plasma sample was collected from each participant along with general health screening examinations before any invasive examinations. We performed low-pass whole-genome sequencing with plasma samples and profiled three types of cell-free DNA (cfDNA) characteristics, fragment size pattern (FSP), copy number variation (CNV), and single nucleotide substitution (SNS). We developed an ensemble model with these differential profiles to identify HNSCC patients from non-cancer individuals. We further collected a validation cohort consisting of 90 HNSCC patients and 95 non-cancer individuals to validate the cfDNA-based assay. Results: The liquid biopsy assay that incorporated three types of cfDNA characteristics was able to identify HNSCC patients from non-cancer individuals at an AUROC of 0.989 in the study cohort and 0.984 in the validation cohort. At a specificity of 95.7% (135/141), it achieved a sensitivity of 95.7% (134/140) in the study cohort. With this threshold (0.580), in the validation cohort, 93.7% (89/95) of non-cancer individuals and 93.3% (84/90) of HNSCC patients were correctly identified. Specifically, the sensitivities in early stage (I&II) HNSCCs were 94.5 % (52/55) and 87.5% (28/32) in the study and validation cohort, respectively. Of note, the inferred probabilities of cancer showed consistent trends to increase with pathological stages in both cohorts (P=0.032 and 0.047, respectively). On the contrary, the differentiation grades and sub-locations did not significantly affect the performance of the assay. Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify HNSCCs from non-cancerous conditions. As a cost-effective non-invasive approach, it may be conveniently incorporated into annual general physical examinations to provide supplementary information about the risk of HNSCCs.
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Devaraja, K., Sadhna Aggarwal, and Manisha Singh. "Therapeutic Vaccination in Head and Neck Squamous Cell Carcinoma—A Review." Vaccines 11, no. 3 (March 13, 2023): 634. http://dx.doi.org/10.3390/vaccines11030634.
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Therapeutic vaccination is one of the most effective immunotherapeutic approaches, second only to immune checkpoint inhibitors (ICIs), which have already been approved for clinical use. Head and neck squamous cell carcinomas (HNSCCs) are heterogenous epithelial tumors of the upper aerodigestive tract, and a significant proportion of these tumors tend to exhibit unfavorable therapeutic responses to the existing treatment options. Comprehending the immunopathology of these tumors and choosing an appropriate immunotherapeutic maneuver seems to be a promising avenue for solving this problem. The current review provides a detailed overview of the strategies, targets, and candidates for therapeutic vaccination in HNSCC. The classical principle of inducing a potent, antigen-specific, cell-mediated cytotoxicity targeting a specific tumor antigen seems to be the most effective mechanism of therapeutic vaccination, particularly against the human papilloma virus positive subset of HNSCC. However, approaches such as countering the immunosuppressive tumor microenvironment of HNSCC and immune co-stimulatory mechanisms have also been explored recently, with encouraging results.
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Nisar, Sabah, Parvaiz Yousuf, Tariq Masoodi, Nissar A. Wani, Sheema Hashem, Mayank Singh, Geetanjali Sageena, et al. "Chemokine-Cytokine Networks in the Head and Neck Tumor Microenvironment." International Journal of Molecular Sciences 22, no. 9 (April 27, 2021): 4584. http://dx.doi.org/10.3390/ijms22094584.
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Head and neck squamous cell carcinomas (HNSCCs) are aggressive diseases with a dismal patient prognosis. Despite significant advances in treatment modalities, the five-year survival rate in patients with HNSCC has improved marginally and therefore warrants a comprehensive understanding of the HNSCC biology. Alterations in the cellular and non-cellular components of the HNSCC tumor micro-environment (TME) play a critical role in regulating many hallmarks of cancer development including evasion of apoptosis, activation of invasion, metastasis, angiogenesis, response to therapy, immune escape mechanisms, deregulation of energetics, and therefore the development of an overall aggressive HNSCC phenotype. Cytokines and chemokines are small secretory proteins produced by neoplastic or stromal cells, controlling complex and dynamic cell–cell interactions in the TME to regulate many cancer hallmarks. This review summarizes the current understanding of the complex cytokine/chemokine networks in the HNSCC TME, their role in activating diverse signaling pathways and promoting tumor progression, metastasis, and therapeutic resistance development.
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Shah, Pooja A., Chenfei Huang, Qiuli Li, Sawad A. Kazi, Lauren A. Byers, Jing Wang, Faye M. Johnson, and Mitchell J. Frederick. "NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma." Cells 9, no. 12 (December 12, 2020): 2677. http://dx.doi.org/10.3390/cells9122677.
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Biomarker-driven targeted therapies are lacking for head and neck squamous cell carcinoma (HNSCC), which is common and lethal. Efforts to develop such therapies are hindered by a genomic landscape dominated by the loss of tumor suppressor function, including NOTCH1 that is frequently mutated in HNSCC. Clearer understanding of NOTCH1 signaling in HNSCCs is crucial to clinically targeting this pathway. Structural characterization of NOTCH1 mutations in HNSCC demonstrates that most are predicted to cause loss of function, in agreement with NOTCH1’s role as a tumor suppressor in this cancer. Experimental manipulation of NOTCH1 signaling in HNSCC cell lines harboring either mutant or wild-type NOTCH1 further supports a tumor suppressor function. Additionally, the loss of NOTCH1 signaling can drive HNSCC tumorigenesis and clinical aggressiveness. Our recent data suggest that NOTCH1 controls genes involved in early differentiation that could have different phenotypic consequences depending on the cancer’s genetic background, including acquisition of pseudo-stem cell-like properties. The presence of NOTCH1 mutations may predict response to treatment with an immune checkpoint or phosphatidylinositol 3-kinase inhibitors. The latter is being tested in a clinical trial, and if validated, it may lead to the development of the first biomarker-driven targeted therapy for HNSCC.
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Munjal, Manish, Shubham Munjal, Vanshika Saggar, Hardeep Kaur, Vineeta Arora, Lovleen Sandhu, Tegbir Singh Binepal, et al. "Epidemiological and clinical presentation of head and neck neoplasia: a review." International Journal Of Community Medicine And Public Health 10, no. 10 (September 30, 2023): 3941–46. http://dx.doi.org/10.18203/2394-6040.ijcmph20233136.
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Head and neck squamous cell carcinoma (HNSCC) stand at the sixth position most, amongst all the malignancies worldwide. Neoplasms arising in the oral cavity, larynx, pharynx, salivary gland and nasal cavity are all included in the head and neck malignancies. More than 90% of malignancies of the oral cavity are squamous cell carcinomas (SCC). Among the four head neck cancer sub-sites combined, the mean age at the time of diagnosis has risen, in the last four decades. Studies have documented a male predilection. A small percentage of SCC cases are inherited or are familial. Cigarette smoking, alcohol consumption, betel quid chewing, poor nutrition, poor oral hygiene, HPV, Epstein-Barr virus and Candida albicans infections are the etiological agents who have the ability to cause HNSCC. Non healing ulcer, difficulty in swallowing, change in voice, swelling, sore throat- that doesn’t get better- are the symptoms of head and neck cancers. Moreover, there may be unusual bleeding, facial swelling or difficulty in breathing.
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Kolenda, Tomasz, Kacper Guglas, Magda Kopczyńska, Anna Teresiak, Renata Bliźniak, Andrzej Mackiewicz, Katarzyna Lamperska, and Jacek Mackiewicz. "Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas." Cells 8, no. 4 (April 21, 2019): 366. http://dx.doi.org/10.3390/cells8040366.
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Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of ZFAS1 and its potential as a biomarker in HNSCC. Methods: The expression level of ZFAS1 in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the ZFAS1 expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. Results: The expression of ZFAS1 was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of ZFAS1 in HNSCCs compared to normal tissue samples. The ZFAS1 levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of ZFAS1 presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with ZFAS1, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of ZFAS1, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between ZFAS1 and its host gene, ZNFX1, was observed. The analysis of interactions indicated that ZFAS1 has a binding sequence for miR-150-5p. The expression of ZFAS1 and miR-150-5p is negatively correlated in HNSCC patients. miR-150-5p can regulate the 3′UTR of EIF4E mRNA. In the group of patients with high expression of ZFAS1 and low expression of miR-150-5p, we detected an up-regulation of EIF4E. Conclusions: In HNSCC, ZFAS1 displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients’ clinical outcomes. ZFAS1 likely regulates the cell phenotype through miR-150-5p and its downstream targets. Following further validation, ZFAS1 might prove a new and valuable biomarker.
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Komínek, Pavel, Petr Vítek, Ondřej Urban, Karol Zeleník, Magdaléna Halamka, David Feltl, Jakub Cvek, and Petr Matoušek. "Chromoendoscopy to Detect Early Synchronous Second Primary Esophageal Carcinoma in Patients with Squamous Cell Carcinomas of the Head and Neck?" Gastroenterology Research and Practice 2013 (2013): 1–5. http://dx.doi.org/10.1155/2013/236264.
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Objective. To evaluate the use of flexible esophagoscopy and chromoendoscopy with Lugol’s solution in the detection of early esophageal carcinomas (second primary carcinomas) in patients with squamous cell carcinoma of the head and neck (HNSCC).Methods. All patients with newly diagnosed HNSCC underwent office-based Lugol's chromoendoscopy. After flexible esophagoscopy with white light, 3.0% Lugol's iodine solution was sprayed over the entire esophageal mucosa. Areas with less-intense staining (LVLs) were evaluated and biopsies taken.Results. 132 patients with HNSCC were enrolled in this study. The most frequent primary tumors were oropharyngeal (49/132), tumors of the oral cavity (36/132), and larynx (35/132). The majority of subjects (107/132 patients, 81.1%) had advanced HNSCC carcinomas (stages III and IV). Multiple LVLs were discovered in 24 subjects (18.2%) and no LVLs in 108 (81.8%) subjects. Fifty-five LVL biopsy specimens were obtained and assessed. Squamous cell carcinomas were detected in two patients, peptic esophagitis in 11 patients, gastric heterotopic mucosa in two patients, hyperplasia in two patients, and low- and high-grade dysplasia in three patients.Conclusion. Although only two patients with synchronous primary carcinomas were found among the patients, esophagoscopy should be recommended after detection of HNSCC to exclude secondary esophageal carcinoma or dysplasia.
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Chimote, Ameet A., Maria A. Lehn, Jay Bhati, Anthony E. Mascia, Mathieu Sertorio, Michael A. Lamba, Dan Ionascu, et al. "Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma." Cancers 16, no. 5 (February 29, 2024): 1008. http://dx.doi.org/10.3390/cancers16051008.
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Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.
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Duray, Anaëlle, Stéphanie Demoulin, Pascale Hubert, Philippe Delvenne, and Sven Saussez. "Immune Suppression in Head and Neck Cancers: A Review." Clinical and Developmental Immunology 2010 (2010): 1–15. http://dx.doi.org/10.1155/2010/701657.
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Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years. The worse prognosis of these cancers must certainly be link to the fact that HNSCCs strongly influence the host immune system. We present a critical review of our understanding of the HNSCC escape to the antitumor immune response such as a downregulation of HLA class I and/or components of APM. Antitumor responses of HNSCC patients are compromised in the presence of functional defects or apoptosis of T-cells, both circulating and tumor-infiltrating. Langerhans cells are increased in the first steps of the carcinogenesis but decreased in invasive carcinomas. The accumulation of macrophages in the peritumoral areas seems to play a protumoral role by secreting VEGF and stimulating the neoangiogenesis.
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Chawla, Sanjeev. "Tumor Hyperprogression in Squamous Cell Carcinomas of Head and Neck after Immunotherapy: Our Perspective." Otolaryngology, Head and Neck Surgery 10, no. 3 (October 30, 2024): 1–6. http://dx.doi.org/10.24966/ohns-010x/100103.
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Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. Although there have been some advances in multimodality therapy, the overall 5-year survival rate remains poor approximately at 40%-50%. Currently, Immune Checkpoint Inhibitor (ICI) based Immunotherapies are being evaluated as an alternate treatment modality for recurrent/metastatic HNSCCs in clinical trials.
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Gharzai, Laila A., Benjamin S. Rosen, Bharat Mittal, Michelle L. Mierzwa, and Poonam Yadav. "Magnetic Resonance Guided Radiotherapy for Head and Neck Cancers." Journal of Clinical Medicine 11, no. 5 (March 3, 2022): 1388. http://dx.doi.org/10.3390/jcm11051388.
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Radiotherapy is an integral component of head/neck squamous cell carcinomas (HNSCCs) treatment, and technological developments including advances in image-guided radiotherapy over the past decades have offered improvements in the technical treatment of these cancers. Integration of magnetic resonance imaging (MRI) into image guidance through the development of MR-guided radiotherapy (MRgRT) offers further potential for refinement of the techniques by which HNSCCs are treated. This article provides an overview of the literature supporting the current use of MRgRT for HNSCC, challenges with its use, and developing research areas.
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Bhatnagar, Aseem Rai, Laura A. Favazza, Suhael R. Momin, and Farzan Siddiqui. "Exploring the Rarity: A Case of Adenosquamous Carcinoma of the Nasal Cavity With Literature Review." Applied Radiation Oncology 13, no. 3 (September 1, 2024): 40–47. https://doi.org/10.37549/aro-d-24-00013.
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Abstract Adenosquamous carcinoma (ADSC) is a rare tumor of the head and neck region, a phenomenon initially delineated by Gerughty and colleagues in 1968. To our knowledge, only 16 cases have been reported with primary ADSC of the nasal cavity (excluding the paranasal sinuses). ADSC is recognized for its aggressive nature and deep tissue infiltration, possessing distinct histomorphology compared with conventional head and neck squamous cell carcinomas (HNSCC) and mucoepidermoid cancers. However, some authors suggest comparable outcomes to conventional HNSCC. Herein, we describe a case report of this uncommon disease and its comprehensive management, along with a brief review of the literature.
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Roschenko, Valeri, Abdallah M. Ayoub, Konrad Engelhardt, Jens Schäfer, Muhammad Umair Amin, Eduard Preis, Robert Mandic, and Udo Bakowsky. "Lipid-Coated Polymeric Nanoparticles for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinomas." Pharmaceutics 15, no. 10 (October 2, 2023): 2412. http://dx.doi.org/10.3390/pharmaceutics15102412.
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Next to alcohol and tobacco abuse, infection with human papillomaviruses (HPVs) is a major risk factor for developing head and neck squamous cell carcinomas (HNSCCs), leading to 350,000 casualties worldwide each year. Limited therapy options and drug resistance raise the urge for alternative methods such as photodynamic therapy (PDT), a minimally invasive procedure used to treat HNSCC and other cancers. We prepared lipid-coated polymeric nanoparticles encapsulating curcumin as the photosensitizer (CUR-LCNPs). The prepared CUR-LCNPs were in the nanometer range (153.37 ± 1.58 nm) and showed an encapsulation efficiency of 92.69 ± 0.03%. Proper lipid coating was visualized using atomic force microscopy (AFM). The CUR-LCNPs were tested in three HPVpos and three HPVneg HNSCC lines regarding their uptake capabilities and in vitro cell killing capacity, revealing a variable but highly significant tumor cell inhibiting effect in all tested HNSCC cell lines. No significant differences were detected between the HPVpos and HPVneg HNSCC groups (mean IC50: (9.34 ± 4.73 µmol/L vs. 6.88 ± 1.03 µmol/L), suggesting CUR-LCNPs/PDT to be a promising therapeutic option for HNSCC patients independent of their HPV status.
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Shin, Eunbie, and Joon Kim. "The potential role of YAP in head and neck squamous cell carcinoma." Experimental & Molecular Medicine 52, no. 8 (August 2020): 1264–74. http://dx.doi.org/10.1038/s12276-020-00492-9.
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Abstract The transcriptional cofactor YAP and its inhibitory regulators, Hippo kinases and adapter proteins, constitute an evolutionarily conserved signaling pathway that controls organ size and cell fate. The activity of the Hippo-YAP pathway is determined by a variety of intracellular and intercellular cues, such as cell polarity, junctions, density, mechanical stress, energy status, and growth factor signaling. Recent studies have demonstrated that YAP can induce the expression of a set of genes that allow cancer cells to gain a survival advantage and aggressive behavior. Comprehensive genomic studies have revealed frequent focal amplifications of the YAP locus in human carcinomas, including head and neck squamous cell carcinoma (HNSCC). Moreover, FAT1, which encodes an upstream component of Hippo signaling, is one of the most commonly altered genes in HNSCC. In this review, we discuss the causes and functional consequences of YAP dysregulation in HNSCC. We also address interactions between YAP and other oncogenic drivers of HNSCC.
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Ramchatesingh, Brandon Liam, and Ivan Litvinov. "Abstract 5734: The effect of PRAME on retinoid response and cell proliferation in cutaneous and head and neck squamous cell carcinoma." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5734. http://dx.doi.org/10.1158/1538-7445.am2022-5734.
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Abstract As cells undergo terminal differentiation, they adopt their tissue-specific functions and permanently exit the cell cycle. Inducing differentiation of premalignant cells and malignant cells are proposed strategies for cancer prevention and treatment, respectively. Retinoids, compounds related to retinol, drive terminal differentiation of numerous cell types. These compounds exhibit efficacy for the prevention of cutaneous squamous cell carcinomas (cSCC) and head and neck squamous cell carcinomas (HNSCCs), and their incorporation into treatment plans for these cancers is supported by laboratory and clinical studies. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer-testis antigen that represses retinoid signaling, and is associated with adverse outcomes in a plethora of malignancies. Although PRAME is known to be expressed in subsets of cutaneous SCC (cSCC) and head and neck SCC (HNSCC) tumors, its functions, prognostic and therapeutic significance have never been investigated in these cancers. We hypothesize that PRAME expression in SCC cells confers resistance to the anti-neoplastic effects of retinoids and supports cell proliferation. PRAME expression was evaluated in human cSCC tumors, and in cSCC and HNSCC cell lines by immunoblotting and qRT-PCR. PRAME-overexpressing immortalized keratinocyte, cSCC and HNSCC cell lines were generated. shRNA-mediated knockdown of PRAME was performed in a cSCC and a HNSCC cell line. Cells were treated with all-trans retinoic acid (ATRA) for 24, 48 or 72 hours. Expression of differentiation markers was assessed by immunoblotting and qRT-PCR of markers of differentiation. Cell counting assays, immunoblot analysis of cell cycle genes and Ki67 immunofluorescence staining were used to assess proliferation. PRAME expression is detected in subsets of cSCC tumors and in select SCC cell lines. Overexpression of PRAME in HNSCC cells enhanced cell proliferation compared to control cells. Treatment with ATRA did not promote differentiation of PRAME-expressing cells. Furthermore, PRAME overexpression attenuated the anti-proliferative effect of ATRA in HNSCC cells. We conclude that PRAME enhances proliferation of malignant keratinocytes in vitro and may confer resistance to retinoid-induced differentiation and proliferation arrest. Investigations to assess the prognostic and therapeutic significance of PRAME expression in SCCs are warranted. Citation Format: Brandon Liam Ramchatesingh, Ivan Litvinov. The effect of PRAME on retinoid response and cell proliferation in cutaneous and head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5734.
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Valentiner, Ursula, Jillian Knips, Ralph Pries, Till Clauditz, Adrian Münscher, Guido Sauter, Barbara Wollenberg, and Udo Schumacher. "Selectin Binding Sites Are Involved in Cell Adhesive Properties of Head and Neck Squamous Cell Carcinoma." Cancers 11, no. 11 (October 28, 2019): 1672. http://dx.doi.org/10.3390/cancers11111672.
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The formation of distant metastases often determines the fate of patients with head and neck squamous cell carcinoma (HNSCC). The expression of cell adhesion molecules (CAMs) and their ligands of the leukocyte adhesion cascade has been associated with metastatic competence in several malignant entities. In this study, human HNSCC cell lines were analyzed in vitro and in a spontaneous metastatic xenograft model. Immunohistochemical analyses of several CAMs were performed on xenograft tumors and tissue microarrays (TMA) from 453 patients with head and neck squamous cell carcinomas with full histo-pathological and clinical follow-up data. UTSCC 24A and 24B cells bind to E-selectin in vitro, show E-selectin dependent binding to human umbilical vein endothelial cells (HUVECs), and express sLeX. All HNSCC cells engrafted into severe combined immunodeficient (SCID) mice, and UTSCC 24A cells formed sporadically spontaneous lung metastases. The expression of CAMs varied between the cell lines, but a correlation between tumor growth and metastatic potential did not exist. None of the CAMS or their ligands could be identified to be of prognostic relevance in the TMA study. The in vitro results indicate that E-selectin and sLeX are involved in the adhesion of HNSCC cells to endothelium. However, specific prognostic markers chosen from the leukocyte adhesion cascade for HNSCC were not identified.
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Krishnamurthy, S., and J. E. Nör. "Head and Neck Cancer Stem Cells." Journal of Dental Research 91, no. 4 (September 20, 2011): 334–40. http://dx.doi.org/10.1177/0022034511423393.
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Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the “drivers” of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy.
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Romanowska, Kamila, Agnieszka Sobecka, Agnieszka A. Rawłuszko-Wieczorek, Wiktoria M. Suchorska, and Wojciech Golusiński. "Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape." Diagnostics 11, no. 1 (December 27, 2020): 34. http://dx.doi.org/10.3390/diagnostics11010034.
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Head and neck squamous carcinoma (HNSCC) constitutes the sixth most prevalent cancer worldwide. The molecular pathogenesis of HNSCC includes disorders in cell cycle, intercellular signaling, proliferation, squamous cell differentiation and apoptosis. In addition to the genetic mutations, changes in HNSCC are also characterized by the accumulation of epigenetic alterations such as DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. In fact, some of them may promote cancer formation and progression by controlling the gene expression machinery, hence, they could be used as biomarkers in the clinical surveillance of HNSCC or as targets for therapeutic strategies. In this review, we focus on the current knowledge regarding epigenetic modifications observed in HNSCC and its predictive value for cancer development.
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Prusinkiewicz, Martin A., Steven F. Gameiro, Farhad Ghasemi, Mackenzie J. Dodge, Peter Y. F. Zeng, Hanna Maekebay, John W. Barrett, Anthony C. Nichols, and Joe S. Mymryk. "Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers." Cancers 12, no. 1 (January 20, 2020): 253. http://dx.doi.org/10.3390/cancers12010253.
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Human papillomavirus (HPV) causes an increasing number of head and neck squamous cell carcinomas (HNSCCs). Altered metabolism contributes to patient prognosis, but the impact of HPV status on HNSCC metabolism remains relatively uncharacterized. We hypothesize that metabolism-related gene expression differences unique to HPV-positive HNSCC influences patient survival. The Cancer Genome Atlas RNA-seq data from primary HNSCC patient samples were categorized as 73 HPV-positive, 442 HPV-negative, and 43 normal-adjacent control tissues. We analyzed 229 metabolic genes and identified numerous differentially expressed genes between HPV-positive and negative HNSCC patients. HPV-positive carcinomas exhibited lower expression levels of genes involved in glycolysis and higher levels of genes involved in the tricarboxylic acid cycle, oxidative phosphorylation, and β-oxidation than the HPV-negative carcinomas. Importantly, reduced expression of the metabolism-related genes SDHC, COX7A1, COX16, COX17, ELOVL6, GOT2, and SLC16A2 were correlated with improved patient survival only in the HPV-positive group. This work suggests that specific transcriptional alterations in metabolic genes may serve as predictive biomarkers of patient outcome and identifies potential targets for novel therapeutic intervention in HPV-positive head and neck cancers.
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Syrjänen, Stina, and Kari Syrjänen. "HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas – Why?" Acta Cytologica 63, no. 2 (2019): 124–42. http://dx.doi.org/10.1159/000495727.
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Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982–1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies. Summary: In this review, the authors first describe the scope (i.e., HNSCC) by the anatomic sites of the tumors. Their important site-specific differences in epidemiology are emphasized, and the misconceptions caused by the adopted practice of pooling all tumors from these divergent anatomic sites as a single entity (HNSCC) are pinpointed. The convincing evidence of the established risk factors (smoking and alcohol) is briefly addressed, before entering in the discussion on the causal role of HPV in HNSCC pathogenesis. The global HPV prevalence in different subsets of HNSCC is summarized using the data extracted from all meta-analyses published since 2010. Of all HNSCC subsets, oropharyngeal SCC has an HPV profile distinct form all the other subsets, and the possible mechanisms explaining this intimate association with HPV are discussed. Key Messages: Recent global trends show a constant increase in HNSCC rates particularly among younger age groups. The evidence on cigarette smoking and alcohol consumption as the prime risk factors of HNSCC is overwhelming. During the past 35 years, however, increasing evidence has accumulated implicating an important causal role of HPV in HNSCC. These data have important clinical implications, HPV detection and tailored treatment strategies for HPV-positive HNSCCs currently being an integral part of the oncological management practices of HNSCC.
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Oton-Gonzalez, Lucia, John Charles Rotondo, Carmen Lanzillotti, Elisa Mazzoni, Ilaria Bononi, Maria Rosa Iaquinta, Luca Cerritelli, et al. "Serum HPV16 E7 Oncoprotein Is a Recurrence Marker of Oropharyngeal Squamous Cell Carcinomas." Cancers 13, no. 13 (July 5, 2021): 3370. http://dx.doi.org/10.3390/cancers13133370.
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Despite improved prognosis for many HPV-positive head and neck squamous cell carcinomas (HNSCCs), some cases are still marked by recurrence and metastasis. Our study aimed to identify novel biomarkers for patient stratification. Classical HPV markers: HPV-DNA, p16 and HPV mRNA expression were studied in HNSCC (n = 67) and controls (n = 58) by qPCR. Subsequently, ELISA tests were used for HPV16 L1 antibody and HPV16 E7 oncoprotein detection in serum at diagnosis and follow-up. All markers were correlated to relapse-free survival (RFS) and overall survival (OS). HPV-DNA was found in HNSCCs (29.85%), HPV16-DNA in 95% of cases, HPV16 E7 mRNA was revealed in 93.75%. p16 was overexpressed in 75% of HPV-positive HNSCC compared to negative samples and controls (p < 0.001). Classical markers correlated with improved OS (p < 0.05). Serological studies showed similar proportions of HPV16 L1 antibodies in all HNSCCs (p > 0.05). Serum E7 oncoprotein was present in 30% HPV-positive patients at diagnosis (p > 0.05) and correlated to HNSCC HPV16 E7 mRNA (p < 0.01), whereas it was associated to worse RFS and OS, especially for oropharyngeal squamous cell carcinoma (OPSCC) (p < 0.01). Detection of circulating HPV16 E7 oncoprotein at diagnosis may be useful for stratifying and monitoring HPV-positive HNSCC patients for worse prognosis, providing clinicians a tool for selecting patients for treatment de-escalation.
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Qin, Tingting, Shiting Li, Leanne E. Henry, Siyu Liu, and Maureen A. Sartor. "Molecular Tumor Subtypes of HPV-Positive Head and Neck Cancers: Biological Characteristics and Implications for Clinical Outcomes." Cancers 13, no. 11 (May 31, 2021): 2721. http://dx.doi.org/10.3390/cancers13112721.
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Until recently, research on the molecular signatures of Human papillomavirus (HPV)-associated head and neck cancers mainly focused on their differences with respect to HPV-negative head and neck squamous cell carcinomas (HNSCCs). However, given the continuing high incidence level of HPV-related HNSCC, the time is ripe to characterize the heterogeneity that exists within these cancers. Here, we review research thus far on HPV-positive HNSCC molecular subtypes, and their relationship with clinical characteristics and HPV integration into the host genome. Different omics data including host transcriptomics and epigenomics, as well as HPV characteristics, can provide complementary viewpoints. Keratinization, mesenchymal differentiation, immune signatures, stromal cells and oxidoreductive processes all play important roles.
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Singh, Paramjit. "ORAL SQUAMOUS CELL CARCINOMA - CASE REPORT." International Journal of Advanced Research 11, no. 10 (October 31, 2023): 963–66. http://dx.doi.org/10.21474/ijar01/17788.
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Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx andlarynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity cancers are generally associated with tobacco consumption, alcohol abuse,exposure to environmental pollutants and infection with viral agents, namely HPV and EBV or both, whereaspharynx cancers are increasingly attributed to infection with humanpapillomavirus (HPV), primarilyHPV-16. Despiteevidence of histological progression from cellular atypia through various degrees of dysplasia,ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident pre malignant lesion.
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Routray, Samapika, and Neeta Mohanty. "Cancer Stem Cells Accountability in Progression of Head and Neck Squamous Cell Carcinoma: The Most Recent Trends!" Molecular Biology International 2014 (February 19, 2014): 1–7. http://dx.doi.org/10.1155/2014/375325.
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Cancer stem cells (CSCs) play a major role in local recurrence and metastatic spread in head and neck squamous cell carcinomas (HNSCC). Evidence suggests that cancer stem cells are resistant to conventional therapy. So the emerging concepts of the role of cancer stem cells in the pathobiology of HNSCC should be understood carefully to be able to create new paradigms in treatment plans.
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Tomita, Hiroyuki. "Comment from the Editor on the Special Issue “Head and Neck Critical Illness: Basic and Clinical Research Implications”." Journal of Clinical Medicine 8, no. 11 (November 7, 2019): 1905. http://dx.doi.org/10.3390/jcm8111905.
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While oncogenic mutations of head and neck squamous cell carcinomas (HNSCC) in head and neck malignancies are uncommon, analysis using next-generation sequencing (NGS) technologies is growing. Further, single-cell analysis is being developed to overcome cancer cell heterogeneity and improve the poor survival of patients. However, it is important for researchers to know how to use this information to improve patients’ survival.
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Perri, Francesco, Francesco Longo, Francesco Caponigro, Fabio Sandomenico, Agostino Guida, Giuseppina Della Vittoria Scarpati, Alessandro Ottaiano, Paolo Muto, and Franco Ionna. "Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat." Cancers 12, no. 4 (April 15, 2020): 975. http://dx.doi.org/10.3390/cancers12040975.
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Head and neck squamous cell carcinomas (HNSCCs) are a very heterogeneous group of malignancies arising from the upper aerodigestive tract. They show different clinical behaviors depending on their origin site and genetics. Several data support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, which show both clinical and biological opposite features. In fact, human papillomavirus (HPV)-related HNSCCs, which are mainly located in the oropharynx, are characterized by better prognosis and response to therapies when compared to HPV-negative HNSCCs. Interestingly, virus-related HNSCC has shown a better response to conservative (nonsurgical) treatments and immunotherapy, opening questions about the possibility to perform a pretherapy assessment which could totally guide the treatment strategy. In this review, we summarize molecular differences and similarities between HPV-positive and HPV-negative HNSCC, highlighting their impact on clinical behavior and on therapeutic strategies.
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da Silva, Flaviane N., Theodore Nguyen, Jong Woo Lee, Barbara Burtness, and Erica Golemis. "Abstract 542: Synthetic lethal targeting of AURKA in head and neck squamous cell carcinoma." Cancer Research 83, no. 7_Supplement (April 4, 2023): 542. http://dx.doi.org/10.1158/1538-7445.am2023-542.
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Abstract The purpose of this study was to identify new combination strategies for improving treatment of head and neck squamous cell carcinomas (HNSCCs). HNSCCs often express high levels of Aurora kinase A (AURKA), most studied as a kinase important for mitotic progression in normal cells. Notably the overexpression of AURKA in many cancers allows it to act throughout the cell cycle, acquiring new cancer-promoting activities. While several AURKA inhibitors are in clinical trials, limited efficacy is observed with single treatment, causing us to evaluate potential AURKA combination therapeutic combinations. Particularly relevant to HNSCC, which often overexpress and depend on EGFR, overexpression of AURKA can promote resistance to EGFR inhibitors by mechanisms variously identified as including activation of the EGFR effectors AKT, ERK, and BIM. Using viability and clonogenic assays, we have found that the AURKA inhibitor VIC-1911 synergizes with the EGFR inhibitors afatinib and erlotinib in multiple HNSCC cell lines and retains activity in HNSCC cell models selected for resistance to these EGFR inhibitors. However, AURKA inhibition increases levels of AURKA protein and its protein-stabilizing partner TPX2, counteracting drug effect. We also combined inhibition of AURKA with inhibition of WEE1, a regulator of the G2/M checkpoint, finding this dual inhibition enhanced levels of apoptosis in EGFR inhibitor resistant HNSCC cell lines. Intriguingly, one recent study reported AURKA can also modulate the glycolytic signaling pathway, increasing the cancer-promoting Warburg effect. We have found that inhibition of AURKA can significantly reduce glycolytic flux in HNSCC cell lines and alter expression and phosphorylation of key glycolytic enzymes. Dual inhibition of AURKA in combination with inhibitors of glycolytic enzymes, or enzymes regulating oxidative phosphorylation, showed marked synergy. These and other results investigating AURKA signaling mechanisms in HNSCC demonstrate that the non-canonical functions of AURKA include viable therapeutic targets that can enhance the efficacy of AURKA inhibition in HNSCC. Citation Format: Flaviane N da Silva, Theodore Nguyen, Jong Woo Lee, Barbara Burtness, Erica Golemis. Synthetic lethal targeting of AURKA in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 542.
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S L, Malaviarachchi. "Quting betel quid - A challenge to Reduce Head & Neck Cancer Incidence in Sri Lanka." Clinical Case Reports and Clinical Study 3, no. 2 (March 29, 2021): 1–3. http://dx.doi.org/10.61148/2766-8614/jccrcs/043.
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Squamous cell carcinoma of Head & Neck is the commonest cancer among males in Sri Lanka. [1] According to National cancer statistics in 2008 by National Cancer Controle Program (NCCP) ; lip oral cavity and pharynx cases were 1860 where as the second commonest among males were lung, trachea and bronchial tumours cancer incidence is 814; which is the second commonest cancer among males in Sri Lanka. According to world statistics in 2008; Head and neck cancers represent the sixth most common cancer with approximately 630,000 new patients diagnosed annually resulting in more than 350,000 deaths every year. [2] More than 90% of head and neck cancers are squamous cell carcinomas (HNSCC) that arise from the mucosal surfaces of the oral cavity.
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Berglund, Anders, Clarisse Muenyi, Erin M. Siegel, Abidemi Ajidahun, Steven A. Eschrich, Denise Wong, Leah E. Hendrick, et al. "Characterization of Epigenomic Alterations in HPV16+ Head and Neck Squamous Cell Carcinomas." Cancer Epidemiology, Biomarkers & Prevention 31, no. 4 (January 21, 2022): 858–69. http://dx.doi.org/10.1158/1055-9965.epi-21-0922.
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Abstract Background: Epigenetic changes associated with human papillomavirus (HPV)–driven tumors have been described; however, HPV type–specific alterations are less well understood. We sought to compare HPV16-specific methylation changes with those in virus-unassociated head and neck squamous cell carcinomas (HNSCC). Methods: Within The Cancer Genome Atlas, 59 HPV16+ HNSCC, 238 nonviral HNSCC (no detectable HPV or other viruses), and 50 normal head and neck tissues were evaluated. Significant differentially methylated regions (DMR) were selected, and key associated genes were identified. Partial least squares models were generated to predict HPV16 status in additional independent samples. Results: HPV infection in HNSCC is associated with type-specific methylomic profiles. Multiple significant DMRs were identified between HPV16+, nonviral, and normal samples. The most significant differentially methylated genes, SYCP2, MSX2, HLTF, PITX2, and GRAMD4, demonstrated HPV16-associated methylation patterns with corresponding alterations in gene expression. Phylogenetically related HPV types (alpha-9 species; HPV31, HPV33, and HPV35) demonstrated a similar methylation profile to that of HPV16 but differed from those seen in other types, such as HPV18 and 45 (alpha-7). Conclusions: HNSCC linked to HPV16 and types from the same alpha species are associated with a distinct methylation profile. This HPV16-associated methylation pattern is also detected in cervical cancer and testicular germ cell tumors. We present insights into both shared and unique methylation alterations associated with HPV16+ tumors and may have implications for understanding the clinical behavior of HPV-associated HNSCC. Impact: HPV type–specific methylomic changes may contribute to understanding biologic mechanisms underlying differences in clinical behavior among different HPV+ and HPV− HNSCC.
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Chinnathambi, P. Sakthidasan, and Deepak Kumar B. "Immunoexpression of cyclin d1 in head and neck squamous cell carcinomas – Correlation with histopathological grade and clinical parameters." IP Journal of Diagnostic Pathology and Oncology 6, no. 2 (June 15, 2021): 99–104. http://dx.doi.org/10.18231/j.jdpo.2021.022.
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Squamous cell carcinomas constitute 95% of cancers of the head and neck region. The progression of disease in these patients depends on various molecular regulators. The present study is undertaken to identify the immunoexpression of Cyclin D1 in Head and Neck Squamous Cell Carcinomas (HNSCC) and to study their association with clinicopathological variables in routine diagnostics.1. To study the expression of Cyclin D1 in Head and Neck Squamous Cell Carcinomas by immunohistochemistry. 2. To correlate the expression of Cyclin D1 with histopathological grading and various demographic parameters.150 cases of HNSCCs were studied for a period of 18 months in ESIC MC & PGIMSR, Bangalore. The cases were subjected to immunohistochemical analysis of Cyclin D1 antigen. Immunoexpression of Cyclin D1 was correlated with histopathological differentiation and clinical parameters.Out of 150 cases; well, moderate and poorly differentiated grades constituted67, 63 and 20 cases respectively. Immunoexpression of Cyclin D1 wasfound in 100 % of the cases and they were significantly associated with worseninggrade of the tumour and positive lymph node disease while it was not found to be associated with other clinical parameters.Immunohistochemical analysis of cyclin D1 can be routinely done inHNSCC as it proves to be an effective, early prognostic indicator in predicting theadvanced stage of the disease and guiding appropriate management.
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Fakhry, Carole, and Maura L. Gillison. "Clinical Implications of Human Papillomavirus in Head and Neck Cancers." Journal of Clinical Oncology 24, no. 17 (June 10, 2006): 2606–11. http://dx.doi.org/10.1200/jco.2006.06.1291.
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Human papillomavirus (HPV) is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and palatine tonsils within the oropharynx. High-risk HPV16 is identified in the overwhelming majority of HPV-positive tumors, which have molecular-genetic alterations indicative of viral oncogene function. Measures of HPV exposure, including sexual behaviors, seropositivity to HPV16, and oral, high-risk HPV infection, are associated with increased risk for oropharyngeal cancer. HPV infection may be altering the demographics of HNSCC patients, as these patients tend to be younger, nonsmokers, and nondrinkers. There is sufficient evidence to conclude that a diagnosis of HPV-positive HNSCC has significant prognostic implications; these patients have at least half the risk of death from HNSCC when compared with the HPV-negative patient. The HPV etiology of these tumors may have future clinical implications for the diagnosis, therapy, screening, and prevention of HNSCC.
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Lefebvre, J. L., A. Joveniaux, A. Caty, J. Ton Van, and L. Adenis. "Epidemiological study of head & neck squamous cell carcinomas (HNSCC)." European Journal of Cancer 29 (January 1993): S125. http://dx.doi.org/10.1016/0959-8049(93)91304-4.
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Kondoh, Nobuo, and Masako Mizuno-Kamiya. "The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas." Cancers 14, no. 12 (June 11, 2022): 2884. http://dx.doi.org/10.3390/cancers14122884.
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HNSCCs are the major progressive malignancy of the upper digestive and respiratory organs. Malignant phenotypes of HNSCCs are regulated by the pro- and anti-tumoral activities of the immune modulatory cytokines associated with TMEs, i.e., a representative pro-inflammatory cytokine, interferon (IFN)-γ, plays a role as an anti-tumor regulator against HNSCCs; however, IFN-γ also drives programmed death-ligand (PD-L) 1 expression to promote cancer stem cells. Interleukin (IL)-2 promotes the cytotoxic activity of T cells and natural killer cells; however, endogenous IL-2 can promote regulatory T cells (Tregs), resulting in the protection of HNSCCs. In this report, we first classified and mentioned the immune modulatory aspects of pro-inflammatory cytokines, pro-/anti-inflammatory cytokines, and anti-inflammatory cytokines upon HNSCC phenotypes. In the TME of HNSCCs, pro-tumoral immune modulation is mediated by stromal cells, including CAFs, MDSCs, pDCs, and TAMs. Therefore, we evaluated the functions of cytokines and chemokines that mediate the crosstalk between tumor cells and stromal cells. In HNSCCs, the status of lymph node metastasis is an important hallmark of a worse prognosis. We therefore evaluated the possibility of chemokines mediating lymph node metastases in HNSCC patients. We also mention therapeutic approaches using anti-tumoral cytokines or immunotherapies that target cytokines, chemokines, or signal molecules essential for the immune evasion of HNSCCs. We finally discuss modulation by HPV infection upon HNSCC phenotypes, as well as the prognostic significance of serum cytokine levels in HNSCC patients.
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Hendawy, Heba A. El, Afaf Ibrahiem, El-Nagdy SY, and Zedan W. "N-cadherin and hyaluronan expression in head and neck squamous cell carcinoma, relation to patient outcomes." Journal of Solid Tumors 8, no. 1 (December 5, 2017): 19. http://dx.doi.org/10.5430/jst.v8n1p19.
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Background: Epithelial-mesenchymal transition (EMT) is regarded as an essential step for tumor invasion and metastasis. In squamous cell carcinoma of head and neck (HNSCC), N-Cadherin expression and its involvement in tumor progression remains a controversial topic.Aim of the study: The present study aimed to assess the expression of N-cadherin and HA in HNSCC and further study their relation to patients survival and outcomes.Material and methods: Fifty-eight retrospective selected cases of head and neck squamous carcinomas (HNSCCs) with available paraffin blocks. Complete clinico-pathological and follow-up data were recorded. Immune staining for N-cadherin and hyaluronan were done, also, we study the correlation of the results with patients survival data.Results: Squamous cell carcinoma islands demonstrated high N-cadherin expression in 55.2% and low expression in 44.8%. N-cadherin high expression was significantly (p < .05) associated with large tumor sizes, advanced TNM clinical stage, increased incidence of recurrence and patient’s death. A significant correlation was recorded between the presence of neural invasion and N-cadherin expression (p = .004). Strong intensity of stromal HA was significantly (p < .05) associated with an oral site, nodal metastasis, and higher TNM stage. Patients with high N-cadherin expression, diffuse hyaluronan, and strong stromal hyaluronanreaction had significantly lower DFS rates (p < .05). High N-cadherin expression, diffuse hyaluronan immunoreactivity, and strong stromal hyaluronan reaction intensity had significantly lower OS rates (p < .05).Conclusion: N-cadherin and hyaluronan could be important and promising biomarkers during surveillance of patients with HNSCC.
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Paluszczak, Jarosław. "The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas." Cells 9, no. 3 (March 15, 2020): 723. http://dx.doi.org/10.3390/cells9030723.
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The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.
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Li, John Zenghong, Wei Gao, Jimmy Yu-Wai Chan, Wai-Kuen Ho, and Thian-Sze Wong. "Hypoxia in Head and Neck Squamous Cell Carcinoma." ISRN Otolaryngology 2012 (October 16, 2012): 1–8. http://dx.doi.org/10.5402/2012/708974.
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Hypoxia is a common feature in most of the solid tumors including head and neck squamous cell carcinoma (HNSCC). Hypoxia reflects the imbalance between oxygen consumption by the rapidly proliferating cancer cells and the insufficient oxygen delivery due to poor vascularization and blood supply. The hypoxic microenvironment in the HNSCC contributes to the development of aggressive carcinoma phenotype with high metastatic rate, resistance to therapeutic agents, and higher tumor recurrence rates, leading to low therapeutic efficiency and poor outcome. To overcome the therapeutic resistance due to hypoxia and improving the prognosis of the HNSCC patients, many approaches have been examined in laboratory studies and clinical trials. In this short paper, we discuss the mechanisms involved in the resistance of radiotherapy and chemotherapy in hypoxic condition. We also exploit the molecular mechanisms employed by the HNSCC cells to adapt the hypoxic condition and their tumorigenic role in head and neck, as well as the strategies to overcome hypoxia-induced therapeutic resistance.
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D’Onofrio, Ida, Valerio Nardone, Alfonso Reginelli, and Salvatore Cappabianca. "Chemoradiotherapy for Head and Neck Cancer." Cancers 15, no. 10 (May 18, 2023): 2820. http://dx.doi.org/10.3390/cancers15102820.
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Griso, Ana Belén, Lucía Acero-Riaguas, Beatriz Castelo, José Luis Cebrián-Carretero, and Ana Sastre-Perona. "Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas." Cells 11, no. 3 (February 5, 2022): 561. http://dx.doi.org/10.3390/cells11030561.
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Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies are emerging, cisplatin-based chemotherapy remains the gold standard for advanced HNSCCs, although most of the patients relapse due to the development of resistance. This review aims to condense the different mechanisms involved in the development of cisplatin resistance in HNSCCs and highlight future perspectives intended to overcome its related complications. Classical resistance mechanisms include drug import and export, DNA repair and oxidative stress control. Emerging research identified the prevalence of these mechanisms in populations of cancer stem cells (CSC), which are the cells mainly contributing to cisplatin resistance. The use of old and new CSC markers has enabled the identification of the characteristics within HNSCC CSCs predisposing them to treatment resistance, such as cell quiescence, increased self-renewal capacity, low reactive oxygen species levels or the acquisition of epithelial to mesenchymal transcriptional programs. In the present review, we will discuss how cell intrinsic and extrinsic cues alter the phenotype of CSCs and how they influence resistance to cisplatin treatment. In addition, we will assess how the stromal composition and the tumor microenvironment affect drug resistance and the acquisition of CSCs’ characteristics through a complex interplay between extracellular matrix content as well as immune and non-immune cell characteristics. Finally, we will describe how alterations in epigenetic modifiers or other signaling pathways can alter tumor behavior and cell plasticity to induce chemotherapy resistance. The data generated in recent years open up a wide range of promising strategies to optimize cisplatin therapy, with the potential to personalize HNSCC patient treatment strategies.
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Aggarwal, Abhishek, Gunjan Jindal, Shubhangi Gupta, and Manisha Ruchandani. "A rare case of peritoneal metastases from oropharyngeal squamous cell carcinoma in a young male after completion of chemoradiotherapy." Journal of Cancer Research and Therapeutics 19, Suppl 2 (2023): S954—S957. http://dx.doi.org/10.4103/jcrt.jcrt_163_22.
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ABSTRACT Distant metastases are frequent in head and neck squamous cell carcinomas (HNSCC), but they are limited to some organs like lungs, bone, mediastinum, liver and brain. Peritoneal metastases (PMs) from HNSCC are extremely rare. A 28-year-old chronic smoker and alcoholic was diagnosed with squamous cell carcinoma of oropharynx. Patient was admitted and was given six cycles of concurrent chemo and radiotherapy (CCRT) and was discharged. Two months later, he presented with abdominal pain and lump. Contrast-enhanced CT revealed ascites, peritoneal implants and subcutaneous deposit which were proved to be metastases by histopathology. The present case is the seventh reported case of PM from HNSCC. • Patients of HNSCC shall be screened for distant metastases. • Differential diagnosis of HNSCC needs consideration when encountered with peritoneal metastases. • Research is required to understand the basis of PM in HNSCC while on CCRT to suggest management modifications.
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Rubin, J. S., B. K. Bloor, I. R. Hart, and P. R. Morgan. "muc-1 gene expression in head and neck squamous cell carcinomas." Journal of Laryngology & Otology 114, no. 10 (October 2000): 772–76. http://dx.doi.org/10.1258/0022215001904121.
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Polymorphic epithelial mucin (PEM), the protein product of the gene muc-1, is a surface glycoprotein that is produced by a range of normal epithelial cells, but has been shown to be expressed at high levels in a range of adenocarcinomas. It has not been investigated extensively in head and neck related tissues, and not at all in head and neck squamous cell carcinomas (HNSCC). This immunohistochemical investigation using two monoclonal antibodies to muc-1 represents a baseline study of 18 HNSCC. In 13 cases, the glycoprotein was expressed at varying levels, usually in keratinizing foci. Although less prominent, expression was also present to some degree in nine of 23 control specimens of non-neoplastic mucosa, mostly at an epithelial level early in the parakeratinization process. Both antibodies showed a pattern of staining. The cellular basis for muc-1 expression is speculative at present and although it is at a lower level than in adenocarcinomas, it may help to provide further insight into epithelial cell differentiation in squamous cell carcinomas.