Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-Fluorouracil with or without docetaxel: retrospective analysis of EORTC24971 study.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 6061-6061
Author(s):  
Amanda Psyrri ◽  
Catherine Fortpied ◽  
George Koutsodontis ◽  
Margaritis Avgeris ◽  
Jessica Menis ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Retrospective Analysis ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv Status ◽  
The Impact

scholarly journals 837 Preliminary insights into the impact of tumor microbiome in head and neck squamous cell carcinoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A878-A878
Author(s):  
Vidhya Karivedu ◽  
Rebecca Hoyd ◽  
Caroline Wheeler ◽  
Sachin Jhawar ◽  
Priyanka Bhateja ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Smoking History ◽  
Predictive Tool ◽  
Hpv Status ◽  
The Impact

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a heterogeneous set of distinct malignancies. Recognized prognostic factors rely on clinical and biological features, consisting mainly of stage, site of disease, performance status, comorbidities, smoking history and human papilloma virus (HPV) status. However, patients clustered by these parameters still differ in their clinical behavior and therapy response. The impact of the tumor microbiome on human disease has been explored and discussed extensively. Evaluating the tumor microbiome is a promising new approach that could be used as a prognostic and predictive tool in HNSCC, with the potential for improved treatment options and better clinical outcomes.MethodsWe utilized The Cancer Genome Atlas (TCGA) database to obtain RNA sequencing (RNAseq) data to identify microbes in HNSCC samples. We utilized ExoTIC, ”Exogenous sequences in Tumors and Immune cells,” a tool recently developed by Spakowicz et al. ExoTIC takes raw RNAseq reads and carefully aligns them to both human and non-human reference genomes to identify low-abundance microbes. We performed Cox proportional hazards regression to identify the microbes associated with overall survival (OS), controlling for age, stage, and smoking status.ResultsWe evaluated 498 RNAseq samples from TCGA (table 1). ExoTIC identified 5838 microbes including bacteria, viruses and fungi, of which 330 were statistically associated with OS. Interestingly, 20% (n=100) of samples had HPV virus which was significantly associated with improved OS (HR 0.59, CI 0.4–0.9, p<0.01). There were also several other viruses and bacteria associated with significantly improved OS.Abstract 837 Table 1Patient characteristics of TCGA datasetConclusionsWe found the presence of certain microbes in tumor biopsies statistically correlated with OS in HNSCC patients. This supports further study into the presence and correlation of specific microbes with tumor subsite and outcomes. Assessing individual characteristics of a HNSCC subtype with its particular microenvironment (e.g., microbes) can lead to personalized treatment insights and improved outcomes. Our future research will validate and correlate the microbial profile of HNSCC subtypes with clinical outcomes retrospectively and prospectively.

scholarly journals Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Javier Fernández-Mateos ◽  
Jéssica Pérez-García ◽  
Raquel Seijas-Tamayo ◽  
Ricard Mesía ◽  
Jordi Rubió-Casadevall ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Clinicopathological Features ◽  
Neck Squamous Cell Carcinoma ◽  
Phase Iii ◽  
Hpv Status

Abstract 234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours.

scholarly journals Prognostic and Predictive Factors in Advanced Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 22 (9) ◽  
pp. 4981
Author(s):  
Teresa Magnes ◽  
Sandro Wagner ◽  
Dominik Kiem ◽  
Lukas Weiss ◽  
Gabriel Rinnerthaler ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Upper Aerodigestive Tract ◽  
Hpv Status

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials.

scholarly journals Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3038
Author(s):  
Mickaël Burgy ◽  
Aude Jehl ◽  
Ombline Conrad ◽  
Sophie Foppolo ◽  
Véronique Bruban ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cell Cycle Progression ◽  
Locally Advanced ◽  
Treatment Resistance ◽  
Neck Squamous Cell Carcinoma ◽  
Hnscc Cell

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.

scholarly journals Disulfiram Acts as a Potent Radio-Chemo Sensitizer in Head and Neck Squamous Cell Carcinoma Cell Lines and Transplanted Xenografts

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 517
Author(s):  
Wenhao Yao ◽  
Xu Qian ◽  
Sebastian Ochsenreither ◽  
Ferrone Soldano ◽  
Albert B. DeLeo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Colony Formation ◽  
Therapeutic Potential ◽  
Synergistic Effects ◽  
Locally Advanced ◽  
Neck Squamous Cell Carcinoma ◽  
Tumor Xenograft

The poor prognosis of locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC) is primarily mediated by the functional properties of cancer stem cells (CSCs) and resistance to chemoradiotherapy. We investigated whether the aldehyde dehydrogenase (ALDH) inhibitor disulfiram (DSF) can enhance the sensitivity of therapy. Cell viability was assessed by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) and apoptosis assays, and the cell cycle and reactive oxygen species (ROS) levels were evaluated by fluorescence-activated cell sorting (FACS). The radio-sensitizing effect was measured by a colony formation assay. The synergistic effects were calculated by combination index (CI) analyses. The DSF and DSF/Cu2+ inhibited the cell proliferation (inhibitory concentration 50 (IC50) of DSF and DSF/Cu2+ were 13.96 μM and 0.24 μM). DSF and cisplatin displayed a synergistic effect (CI values were <1). DSF or DSF/Cu2+ abolished the cisplatin-induced G2/M arrest (from 52.9% to 40.7% and 41.1%), and combining irradiation (IR) with DSF or DSF/Cu2+ reduced the colony formation and attenuated the G2/M arrest (from 53.6% to 40.2% and 41.9%). The combination of cisplatin, DSF or DSF/Cu2+, and IR enhanced the radio-chemo sensitivity by inducing apoptosis (42.04% and 32.21%) and ROS activity (46.3% and 37.4%). DSF and DSF/Cu2+ enhanced the sensitivity of HNSCC to cisplatin and IR. Confirming the initial data from patient-derived tumor xenograft (PDX) supported a strong rationale to repurpose DSF as a radio-chemosensitizer and to assess its therapeutic potential in a clinical setting.

Sign in / Sign up

Export Citation Format

Share Document