scholarly journals Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer

2017 ◽  
Author(s):  
Farhoud Faraji ◽  
Munfarid Zaidi ◽  
Carole Fakhry ◽  
Daria A. Gaykalova
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Specific Data ◽  
Genome Wide

ABSTRACTThis review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamous cell carcinoma in areas for which specific data is available. It covers the major pathways dysregulated in HPV- positive HNSCC and the genome-wide changes associated with this disease.

Head and Neck Cancer

2018 ◽  
Author(s):  
Everett E Vokes ◽  
Kevin C. Wood
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Trials ◽  
Head And Neck Cancer ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Early Stage Disease ◽  
Metastatic Setting

The most common histology of non-thyroid head and neck cancer is squamous cell carcinoma.  Common risk factors for head and neck malignancies include tobacco and alcohol abuse and viruses, including Epstein-Barr Virus (EBV) and Human Papillomavirus (HPV). Early stage disease is often treated with surgery or radiation therapy alone, while more advanced disease often requires a multi-modality approach including systemic chemotherapy, radiation, and surgical resection.  In the curative setting, current clinical trials are evaluating the de-escalation of therapy in HPV-releated head and neck cancer.  In the metastatic setting, clinical trials have focused on using immunotherapy agents to improve outcomes. This review chapter will discuss the etiology and common presentations of head and neck cancer, and also analyze recent advancements in the treatment of the disease.          Key words: chemoradiation, head and neck cancer, human papillomavirus, immunotherapy, oropharynx, squamous cell carcinoma, treatment deescalation

Head and Neck Cancer

2018 ◽  
Author(s):  
Everett E Vokes ◽  
Kevin C. Wood
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Trials ◽  
Head And Neck Cancer ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Early Stage Disease ◽  
Metastatic Setting

The most common histology of non-thyroid head and neck cancer is squamous cell carcinoma.  Common risk factors for head and neck malignancies include tobacco and alcohol abuse and viruses, including Epstein-Barr Virus (EBV) and Human Papillomavirus (HPV). Early stage disease is often treated with surgery or radiation therapy alone, while more advanced disease often requires a multi-modality approach including systemic chemotherapy, radiation, and surgical resection.  In the curative setting, current clinical trials are evaluating the de-escalation of therapy in HPV-releated head and neck cancer.  In the metastatic setting, clinical trials have focused on using immunotherapy agents to improve outcomes. This review chapter will discuss the etiology and common presentations of head and neck cancer, and also analyze recent advancements in the treatment of the disease.          Key words: chemoradiation, head and neck cancer, human papillomavirus, immunotherapy, oropharynx, squamous cell carcinoma, treatment deescalation

Follow-up strategies in head and neck cancer other than upper aerodigestive tract squamous cell carcinoma

2012 ◽  
Vol 270 (7) ◽  
pp. 1981-1989 ◽  
Author(s):  
Antoine Digonnet ◽  
Marc Hamoir ◽  
Guy Andry ◽  
Vincent Vander Poorten ◽  
Missak Haigentz ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Aerodigestive Tract ◽  
Upper Aerodigestive Tract

Squamous cell carcinoma DNA detection using ultrabright SERS nanorattles and magnetic beads for head and neck cancer molecular diagnostics

2017 ◽  
Vol 9 (37) ◽  
pp. 5550-5556 ◽  
Author(s):  
P. Vohra ◽  
H. T. Ngo ◽  
W. T. Lee ◽  
T. Vo-Dinh
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Molecular Diagnostics ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Magnetic Beads ◽  
Low Cost ◽  
Diagnostic Technologies

A rise in head and neck cancers in low and middle countries over recent years has prompted the need for low-cost, resource-efficient diagnostic technologies.

scholarly journals 903 Human cancer-associated fibroblast subsets can predict immune checkpoint response in head and neck cancer patients

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A947-A947
Author(s):  
Diana Graves ◽  
Aleksandar Obradovic ◽  
Michael Korrer ◽  
Yu Wang ◽  
Sohini Roy ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Single Cell ◽  
Rna Sequencing ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Single Cell Rna Sequencing

BackgroundUse of anti-PD-1 immune checkpoint inhibitors (ICI) is currently the first line therapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but critical work remains in identifying factors guiding resistance mechanisms.1 2 While recent studies have specifically implicated cancer-associated fibroblasts (CAFs) as potential mediators of immunotherapy response, the immunoregulatory role of CAFs in head and neck cancer has not been thoroughly explored.3–5MethodsTo determine if there are changes in cell populations associated with anti-PD-1 therapy in head and neck cancer patients, we performed high dimensional single-cell RNA sequencing (scRNA-SEQ) from a neoadjuvant trial of 50 advanced-stage head and neck squamous cell carcinoma (HNSCC) patients that were treated with the anti-PD-1 therapy, nivolumab, for the duration of one month. Tumor specimens were analyzed pre- and post-treatment with single-cell RNA sequencing performed on 4 patients as well as bulk RNA sequencing on 40 patients. Matched scRNA-SEQ data was analyzed using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and Virtual Inference of Protein-activity by Enriched Regulon (VIPER) bioinformatic analysis platform to determine TME cells that correlated with response and resistance to nivolumab.6 For CAF functional studies, surgical tumor specimens were processed and enriched for CAF subtypes, and these were co-cultured with T cells from peripheral blood and tumor infiltrating lymphocytes.ResultsWe identified 14 distinct cell types present in HNSCC patients. Of these 14 cell types, the fibroblast subtype showed significant changes in abundance following nivolumab treatment. We identified 5 distinct clusters of cancer-associated fibroblast subsets (HNCAF-0, 1, 2, 3, and 4) of which, two clusters, HNCAF-0 and HNCAF-3 were predictive of patient response to anti-PD-1 therapy. To determine the significance of these CAF subsets’ function, we isolated HNCAF-0/3 cells from primary HNSCC tumor specimens and co-cultured with primary human T cells. Analysis by flow cytometry showed that HNCAF-0/3 reduced TGFβ-dependent PD-1+TIM-3+ exhaustion of T cells and increased CD103+NKG2A+ resident memory phenotype and cytotoxicity to enhance overall function.ConclusionsTo our knowledge, we are the first to characterize CAF heterogeneity within the head and neck TME and show direct immunostimulatory activity of CAFs. Our findings demonstrate the functional importance of CAF subsets in modulating the immunoregulatory milieu of the human HNSCC, and we have identified clinically actionable CAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.Trial RegistrationNCT03238365ReferencesFerris RL, Blumenschein Jr G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016;375:1856–1867.Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol 2016;17:956–965.Dominguez CX, Muller S, Keerthivasan S, Koeppen H, Hung J, Gierke S, Breart B, Foreman O, Bainbridge TW, Castiglioni A, et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov 2020;10:232–253.Feig C, Jones JO, Kraman M, Wells RJ, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A 2013;110:20212–20217.Kieffer Y, Hocine HR, Gentric G, Pelon F, Bernard C, Bourachot B, Lameiras S, Albergante L, Bonneau C, Guyard A, et al. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discov 2020;10:1330–1351.Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, Guo XV, Aggen DH, Rathmell WK, Jonasch E, et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 2021;184:2988–3005.Ethics ApprovalPatients provided informed consent for this work. All experimental procedures were approved by the Institutional Review Board of Vanderbilt University Medical Center (IRB: 171883).

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