Molecular profiling and survival outcomes of p16+ compared to p16- oropharynx squamous cell cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18026-e18026
Author(s):  
Brittany Nicole Hughes ◽  
Hira Ghazal Shaikh ◽  
Julie Elaine McGrath ◽  
Joanne Xiu ◽  
Ammar Sukari ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Life Sciences ◽  
Molecular Profiling ◽  
Missense Mutations ◽  
Targeted Next Generation Sequencing ◽  
Hpv Status ◽  
Number Of Patients ◽  
Notch1 Mutations

e18026 Background: Previous studies have consistently shown that p16+ oropharynx squamous cell cancer (OPSCC) patients have better outcomes. The significance of molecular and transcriptional signatures and its correlation with p16 expression remains unclear. Methods: We queried the Caris Life Sciences database to assess the molecular and transcriptional signatures related to p16+ and p16- head and neck squamous cell cancer (HNSCC) patients. Comprehensive molecular profiling including whole exome sequencing (WES), targeted Next-Generation Sequencing (NGS), and immunohistochemistry (IHC) 22c3 for PD-L1 was performed (CPS ≥1 considered positive) (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations. A standard cut-off of 2+, > 70% p16 staining was used. HPV16/18 was tested using WES. Patients were considered smokers if they had > 15 pack-years. Real world overall survival (rwOS) was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of start of treatment to the date of last contact. Results: 948 cases of OPSCC were identified in the Caris database. 41% (82/199) were smokers. Where p16 and HPV data was available, 41% were p16+ (171/420) while HPV positivity rate was 52% (71/148). We noted a small number of patients with discordant p16 and HPV status (7 p16+/HPV-, 8 p16-/HPV+) in 327 patients who had HPV status available. Most common mutations were TP53 (33%), PIK3CA (17%) and KMT2D (10.6%). 87% were PD-L1 positive (342/394), with high expression in both p16+ and p16- subgroups, 90% and 85% respectively. 10% had TMB≥10/Mb (48/463). TP53 mutations were more common in p16- (49%) tumors in contrast to p16+ (10%) (p < 0.0005), while no statistical difference was detected in TMB≥10/Mb between the groups. CDKN2A, TERT and NOTCH1 mutations were more prevalent in tumors that were p16- or HPV- in contrast to tumors that were p16+ or HPV+ (p < 0.05). FGF3, CCND1, FGF4, FGF19 copy number alterations (CNA) were less common in p16+ OPSCC compared to p16- or HPV16- OPSCC (p < 0.0005). P16+ patients had longer rwOS when compared to p16-, 47 months versus 20 months (HR = 0.55, p = 0.014) respectively. Conclusions: Higher frequency of CDKN2A, TERT and NOTCH1 mutations among p16- (versus p16+) raise the possibility of potential targets for treatment in this group with poor prognosis. However, it remains unclear if these can serve as independent predictors of survival.[Table: see text]

scholarly journals Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer

2017 ◽  
Author(s):  
Raquel L. Costa ◽  
Mariana Boroni ◽  
Marcelo A. Soares
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Regulatory Elements ◽  
Keratinocyte Differentiation ◽  
External Information ◽  
Hpv Status ◽  
Neck Squamous Cell Cancer

The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). However, a comprehensive understanding of disease progression profiles comparing HPV+ and HPV- HNSCC cases is still lacking. The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV- HNSCC and to provide insights into potential regulatory mechanisms/effects (such as methylation and mutation) within the analyzed networks. For conducting this, we selected 276 samples from The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information (HPV status and tumor staging). We further added external information such as the identification of transcription factors to the networks. Genes were selected as differentially expressed and differentially methylated based on HPV status, of which 12 genes were doubly selected, including SYCP2, GJB6, FLRT3, PITX2 and CCNA1. Weight correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three main modules were associated with distinct co-expression patterns in HPV+ versus HPV- HNSCC. The molecular signatures found were mainly related to cell fate specification, keratinocyte differentiation, focal adhesion and regulation of protein oligomerization. This study provides comprehensive insights into complex genetic and epigenetic particularities in the development and progression of HNSCC in patients according to HPV status, identifying unseen gene interactions, and may contribute to unveiling specific genes/pathways as novel therapeutic targets for HNSCC.

scholarly journals Growth Factor Receptor Expression in Oropharyngeal Squamous Cell Cancer: Her1–4 and c-Met in Conjunction with the Clinical Features and Human Papillomavirus (p16) Status

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3358
Author(s):  
Eric Deuss ◽  
Dorothee Gößwein ◽  
Désirée Gül ◽  
Stefanie Zimmer ◽  
Sebastian Foersch ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Growth Factor ◽  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Clinicopathological Parameters ◽  
Primary Tumors ◽  
Hpv Status

This study aimed to assess the distribution of growth factor receptors in oropharyngeal squamous cell cancer (OPSCC) and evaluate their role in the context of human papillomavirus (HPV) status, prognosis and potential relevance for targeted therapy. The protein expression of human epidermal growth factor receptor (Her)1–4 and c-Met were retrospectively assessed using semiquantitative immunohistochemistry on tissue microarrays and analyzed for correlations as well as differences in the clinicopathological criteria. Her1–4 and c-met were overexpressed compared to normal mucosa in 46%, 4%, 17%, 27% and 23%, respectively. Interestingly, most receptors were coexpressed. Her1 and c-Met were inversely correlated with p16 (p = 0.04; p = 0.02). Her2 and c-Met were associated with high tobacco consumption (p = 0.016; p = 0.04). High EGFR, Her3, Her4 and c-Met expression were associated with worse overall and disease-free survival (p ≤ 0.05). Furthermore, EGFR and c-Met expression showed raised hazard ratios of 2.53 (p = 0.02; 95% CI 1.24–5.18) and 2.45 (p = 0.02; 95% CI 1.13–5.35), respectively. Her4 was expressed less in distant metastases than in corresponding primary tumors and was correlated to a higher T category. EGFR and c-Met are relevant negative prognostic factors in OPSCC, independent of known clinicopathological parameters. We suggest dual targeting of EGFR and c-Met as a promising strategy for OPSCC treatment.

Impact of HPV status on treatment of squamous cell cancer of the oropharynx: What we know and what we need to know

2011 ◽  
Vol 304 (2) ◽  
pp. 71-79 ◽  
Author(s):  
Silke Tribius ◽  
Anna S. Ihloff ◽  
Thorsten Rieckmann ◽  
Cordula Petersen ◽  
Markus Hoffmann
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Cancer ◽  
Cell Cancer ◽  
Hpv Status

scholarly journals Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1714
Author(s):  
Stijn J. De De Keukeleire ◽  
Tijl Vermassen ◽  
Elien Hilgert ◽  
David Creytens ◽  
Liesbeth Ferdinande ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Squamous Cell Cancer ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Predictive Biomarkers ◽  
Clinical Staging ◽  
Hpv Status

The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less-known prognostic and predictive biomarkers. The clinical staging, p16/HPV status, and PD-L1 expression are currently the main tools for assessing the patients’ diagnosis and prognosis. However, several novel biomarkers have been thoroughly investigated, some reaching actual significant clinical contributions. The untangling of the immune infiltrate with the subtyping of tissue-associated tumor infiltrating lymphocytes, tumor-associated macrophages, and circulating blood-based biomarkers are an interesting avenue to be further explored and prospectively assessed. Although PD-L1 expression remains the most important response predictor for immune checkpoint inhibitors, several flaws impede proper assessment such as technical issues, different scoring protocol, and intra-, inter,- and temporal heterogeneity. In addition, the construction of an immune-related gene panel has been proposed as a prognostic and predictive stratification but lacks consensus. Recently, the role of microbioma have also been explored regarding its systemic and antitumor immunity. This review gives a comprehensive overview of the aforementioned topics in SCCHN. To this end, the integration of these clinically advantageous biomarkers via construction of an immunogram or nomogram could be an invaluable tool for SCCHN in future prospects.

Genomic characterization of p16+ compared to p16- HNSCC patients treated with immune checkpoint inhibitors and overall survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18024-e18024
Author(s):  
Hira Ghazal Shaikh ◽  
Julie Elaine McGrath ◽  
Joanne Xiu ◽  
Brittany Nicole Hughes ◽  
Ammar Sukari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Life Sciences ◽  
Gene Mutations ◽  
Missense Mutations ◽  
Significant Difference

e18024 Background: Multiple studies investigating immune checkpoint inhibitors (ICI) in head and neck squamous cell cancer (HNSCC) patients have demonstrated prolonged survival of p16+ versus p16- tumors. However, the data has been conflicting. Methods: We queried the Caris Life Sciences CODEai database to assess survival outcomes of HNSCC patients who received ICIs comparing p16+ and p16- subgroups. A standard cut-off of 2+, >70% p16 staining was used. Presence of HPV16/18 genomes was tested using whole exome sequencing. Patients were considered smokers if they had >15 pack-years of tobacco use. PD-L1 expression was assessed by the 22c3 antibody, ≥1 being positive. Gene mutations were evaluated using Next-Generation Sequencing (NGS) (Caris Life Sciences, Phoenix, AZ). Tumor mutational burden (TMB) was assessed by somatic nonsynonymous missense mutations. Real world overall survival (rwOS) was obtained from insurance claims data and Kaplan-Meier estimates were calculated from the date of treatment start to the date of last contact. Time on treatment (TOT) was calculated from date of start to completion of ICIs. Results: 2905 patients with HNSCC were identified in the Caris database. 41% (215/525) were smokers. Among patients who were tested for p16 and/or HPV, 32% (251/791) expressed p16 and 28% (91/236) were HPV+. The majority of p16+ tumors were oropharynx (OP) in origin (68%, 171/251). 87% (970/1111) of tumors expressed PD-L1 and 16% (216/1362) had TMB ≥10/Mb. TP53 (54%, n=1115/2076) and CDKN2A (17%, n=281/1649) were the most common mutations. When compared to p16-, the p16+ group had a higher prevalence of TMB ≥10/Mb (26% vs 17%) and RB1 mutations (21% vs 4%) but lower number of smokers (15% vs 34%) and TP53 mutations (32% vs 58%). Similar to previous reports, p16+ oropharynx squamous cell carcinoma (OPSCC) patients survived longer than p16- patients, rwOS, 47 vs. 20 months (HR=0.55, p = 0.014) respectively. Among patients who were treated with ICIs, p16+ and p16- non-OP HNSCC, rwOS was not reached (NR) for both groups at follow up of 22 months while TOT for p16+ and p16- respectively, was 3.5 vs. 2.7 months, HR 0.507, p=0.039. No statistically significant difference was found in rwOS (19.3 vs. 24 months, HR 1.8, p=0.27) or TOT (3.7 vs. 4.1 months, HR 0.78, p=0.38) between p16+ and p16- OPSCC groups treated with ICIs, respectively. Conclusions: P16+ non-OP HNSCC patients receiving ICIs were found to remain on treatment longer compared to p16- patients which was not reproduced in the OPSCC subgroup. Randomized controlled trials are needed to verify p16 as a prognostic marker for ICI therapy.[Table: see text]

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