An Immunocompetent Mouse Model of HPV16(+) Head and Neck Squamous Cell Carcinoma

Publication date: 5 November 2019Source: Cell Reports, Volume 29, Issue 6Author(s): Miranda B. Carper, Scott Troutman, Bethany L. Wagner, Kevin M. Byrd, Sara R. Selitsky, Kshitij Parag-Sharma, Erin C. Henry, Weimin Li, Joel S. Parker, Stephanie A. Montgomery, John L. Cleveland, Scott E. Williams, Joseph L. Kissil, David N. Hayes, Antonio L. AmelioSummaryThe incidence of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasing and implicated in more than 60% of all oropharyngeal carcinomas (OPSCCs). Although whole-genome, transcriptome, and proteome analyses have identified altered signaling pathways in HPV-induced HNSCCs, additional tools are needed to investigate the unique pathobiology of OPSCC. Herein, bioinformatics analyses of human HPV(+) HNSCCs revealed that all tumors express full-length E6 and identified molecular subtypes based on relative E6 and E7 expression levels. To recapitulate the levels, stoichiometric ratios, and anatomic location of E6/E7 expression, we generated a genetically engineered mouse model whereby balanced expression of E6/E7 is directed to the oropharyngeal epithelium. The addition of a mutant PIK3CAE545K allele leads to the rapid development of pre-malignant lesions marked by immune cell accumulation, and a subset of these lesions progress to OPSCC. This mouse provides a faithful immunocompetent model for testing treatments and investigating mechanisms of immunosuppression.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

Related Links:

AbstractIn patients with locally advanced human papillomavirus (HPV)-unrelated head and neck squamous-cell carcinoma (HNSCC), cisplatin and radiation therapy (CisRT) resulted in a local –regional recurrence (LRR) rate of 35%, progression-free survival (PFS) of 49%, and overall survival (OS) of 60%. We, and others, showed thatnab-paclitaxel is an active agent in metastatic and locally advanced HNSCC. The aim of this report was to assess the efficacy ofnab-paclitaxel-based induction chemotherapy and CisRT in HPV-unrelated HNSCC. We performed a retrospective single-institution analysis of patients treated withnab-paclit...
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
Abstract Background: An alarming increase in incidence of high-risk human papillomavirus (HPV) positive tumors in head and neck squamous cell carcinoma (HNSCC) by 25% and 70% in oropharyngeal HNSCC cannot be ignored. The early oncogenes of HPV, E6, and E7 play a key role in carcinogenesis. HPV associated tumors have a better clinical outcome and a favorable prognosis. The p16 expression has high concordance with other methods of HPV detection, ascertaining p16 as a surrogate marker for HPV. Objective: To assess the immunohistochemical expression of p16 in oral submucous fibrosis (OSF) and oral squamous cell c...
Source: Indian Journal of Pathology and Microbiology - Category: Pathology Authors: Tags: Indian J Pathol Microbiol Source Type: research
This study investigates the performance of label-free, reflectance-based hyperspectral imaging (HSI) and autofluorescence imaging for SCC detection at the cancer margin in excised tissue specimens from 102 patients and uses fluorescent dyes for comparison. Fresh surgical specimens (n = 293) were collected during H and N SCC resections (n = 102). The tissue specimens were imaged with reflectance-based HSI and autofluorescence imaging and afterwards with two fluorescent dyes for comparison. A histopathological ground truth was made. Deep learning tools were developed to detect SCC with new patient samples (inter-patient) and...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Head and neck squamous cell carcinoma (HNSCC) represents a group of tumors arisng in the oral cavity, oropharynx and larynx. Although HNSCC is traditionally associated with tobacco and alcohol consumption, a growing proportion of head and neck tumors, mainly of the oropharynx, are associated with Human Papilloma Virus (HPV). Recurrent/metastatic disease is characterized by dismal prognosis and there is an unmet need for the development of biomarkers for detection of early disease, accurate prediction of prognosis and appropriate selection of therapy. Based on the REMARK guidelines, a variety of diagnostic and prognostic bi...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: High stromal HA and expression of HA in both tumors and stroma were correlated with poor prognosis in HPV-negative oral cavity cancer, but not in HPV-negative oropharyngeal cancers. PMID: 31352717 [PubMed - as supplied by publisher]
Source: The Korean Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Korean J Intern Med Source Type: research
In conclusion, HPV-DNA prevalence was significantly lower in our HNSCC patients than worldwide 32–36% estimates (p ≤ 0.001). Although infrequent, oropharyngeal cancer increased over years and showed 21% HPV-DNA positivity, which is close to the worldwide 36–46% estimates (p = 0.16). Besides age, smoking, tumor stage, and treatment, HPV/p16 status was an important determinant of patients’ survival. The HPV and/or p16 positivity patients had a better OS than HPV/p16 double-negative patients (p = 0.05). Thus, HPV/p16 status helps improve prognosis by distinguishing between the more favorab...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This article reviews the accumulated evidence on the role of cetuximab in HNSCC in the past decade, offering an overview of its current impact in the treatment of LA and R/M-HNSCC disease and its potential use in the era of immunotherapy.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Aboagye E, Agyemang-Yeboah F, Duduyemi BM, Obirikorang C Abstract Fewer studies have been done over the years to establish the association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSSC) within the subregions of sub-Saharan Africa, and thus this study was designed to investigate the presence of HPV in HNSCC at a tertiary hospital in Ghana, providing additional evidence on the need to explore similar studies in other subregions. A retrospective cross-sectional study was employed to investigate the presence of the DNA of HPV genotypes in HNSCC archived tissue. A total of 100 ...
Source: The Scientific World Journal - Category: Science Tags: ScientificWorldJournal Source Type: research
Santosh K. Ghosh1*, Thomas S. McCormick1,2 and Aaron Weinberg1* 1Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, United States 2Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, United States Human beta-defensins (hBDs, −1, 2, 3) are a family of epithelial cell derived antimicrobial peptides (AMPs) that protect mucosal membranes from microbial challenges. In addition to their antimicrobial activities, they possess other functions; e.g., cell activation, proliferation, regulation of cytokine/chemokine production, migration, diffe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
The objective of this review article is to discuss the current role of surgery as the primary treatment modality in patients with head and neck squamous cell carcinoma (HNSCC). Recent findings HNSCC represents one of the cancer locations where the primary treatment modality is the most under discussion. Indeed, the respective roles of primary surgical resection followed, as necessary, by adjuvant radiotherapy or definitive chemoradiotherapy remain controversial. The results of organ preservation trials and the drastic rise in the incidence of human papillomavirus-induced oropharyngeal tumors, which are known to be highl...
Source: Current Opinion in Oncology - Category: Cancer & Oncology Tags: HEAD AND NECK: Edited by Joël Guigay Source Type: research
More News: Cancer & Oncology | Carcinoma | Cytology | Genetics | HNSCC | Human Papillomavirus (HPV) | Oropharyngeal Cancer | Skin Cancer | Squamous Cell Carcinoma