Comparing ERCC1 protein expression, mRNA levels, and genotype in squamous cell carcinomas of the head and neck treated with concurrent chemoradiation stratified by HPV status

Head & Neck ◽  
2011 ◽  
Vol 34 (6) ◽  
pp. 785-791 ◽  
Author(s):  
Desirée Hao ◽  
Harold Y. Lau ◽  
Misha Eliasziw ◽  
Alan Box ◽  
Román Diaz ◽  
...  
Keyword(s):  
Protein Expression ◽  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Concurrent Chemoradiation ◽  
Mrna Levels ◽  
Hpv Status

Utilization of P16 in Head and Neck Cytology and Surgical Specimens After the Release of CAP Guidelines

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S22-S22
Author(s):  
H Laharwani ◽  
V Manucha ◽  
G Jefferson ◽  
L Jackson
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Common Reason ◽  
Unknown Primary ◽  
Hpv Testing ◽  
Neck Masses ◽  
P16 Immunohistochemistry ◽  
Hpv Status ◽  
Wrong Site

Abstract Introduction/Objective HPV-positive oropharyngeal squamous cell carcinoma is biologically and clinically unique and has a survival advantage over other head and neck squamous cell carcinomas. In December 2017 College of American Pathologist published guidelines for testing HPV status in head and neck cancer. It was recommended that pathologists perform HR-HPV testing on head and neck squamous cell carcinomas from all patients with known oropharyngeal SCC not previously tested for HR-HPV, with suspected oropharyngeal SCC, or with metastatic SCC of unknown primary. The aim of this study was to determine the compliance of pathologists following the CAP guidelines. Methods Cases that underwent HPV testing using p16 immunohistochemistry for the years 2017 and 2019 were retrieved. Based on the guidelines, p16 testing was designated as “indicated” or “not indicated”. Results There were 196 cases in which p16 testing was performed in a period of 3 consecutive years. Of these, 175 were FNA/ biopsies and 21 were surgical resections. In 69 cases (56 FNAs and 13 biopsies) the biopsy was performed on neck masses with unknown primary. The compliance for p16 testing in OPC and Lymph nodes with metastatic SCC of unknown primary was 100%. In 34 (17.3%) cases p16 testing was not indicated, the most common reason being wrong site (85%) including the larynx, oral tongue, the floor of the mouth, buccal mucosa, and nasal mass. Of the unindicated p16s, 20 (58%) were received in consultation for continuity of care. Conclusion Not being clear about the site of the tumor is the most common reason for unindicated p16 testing. A clear designation of biopsy site and proper communication between pathologist and surgeon can improve utilization of p16 testing in head and neck carcinomas.

scholarly journals Human Papillomavirus Drives Tumor Development Throughout the Head and Neck: Improved Prognosis Is Associated With an Immune Response Largely Restricted to the Oropharynx

2016 ◽  
Vol 34 (34) ◽  
pp. 4132-4141 ◽  
Author(s):  
Ankur Chakravarthy ◽  
Stephen Henderson ◽  
Stephen M. Thirdborough ◽  
Christian H. Ottensmeier ◽  
Xiaoping Su ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Human Papillomavirus ◽  
Head And Neck ◽  
Squamous Cell ◽  
Survival Data ◽  
Squamous Cell Carcinomas ◽  
Causal Role ◽  
Anatomic Site ◽  
Hpv Status

Purpose In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors. Methods Meta-analysis was used to build a cross-tissue gene-expression signature for HPV-driven cancer. Classifiers trained by machine-learning approaches were used to predict the HPV status of 520 HNSCCs profiled by The Cancer Genome Atlas project. DNA methylation data were similarly used to classify 464 HNSCCs and these analyses were integrated with genomic, histopathology, and survival data to permit a comprehensive comparison of HPV transcript-positive OPSCC and non-OPSCC. Results HPV-driven tumors accounted for 4.1% of non-OPSCCs. Regardless of anatomic site, HPV+ HNSCCs shared highly similar gene expression and DNA methylation profiles; nonkeratinizing, basaloid histopathological features; and lack of TP53 or CDKN2A alterations. Improved overall survival, however, was largely restricted to HPV-driven OPSCCs, which were associated with increased levels of tumor-infiltrating lymphocytes compared with HPV-driven non-OPSCCs. Conclusion Our analysis identified a causal role for HPV in transcript-positive non-OPSCCs throughout the head and neck. Notably, however, HPV-driven non-OPSCCs display a distinct immune microenvironment and clinical behavior compared with HPV-driven OPSCCs.

Analysis of High-Risk HPV Status in Squamous Cell Carcinomas of the Head and Neck from June 2013-March 2014

2014 ◽  
Vol 3 (5) ◽  
pp. S49
Author(s):  
Lisa Ring ◽  
Brenda Sweeney ◽  
Ronald Arpin ◽  
Heather Grant ◽  
Mary Rego ◽  
...  
Keyword(s):  
High Risk ◽  
Head And Neck ◽  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Hpv Status ◽  
High Risk Hpv

scholarly journals Death agonist antibody against TRAILR2/DR5/TNFRSF10B enhances birinapant anti-tumor activity in HPV-positive head and neck squamous cell carcinomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi An ◽  
Jun Jeon ◽  
Lillian Sun ◽  
Adeeb Derakhshan ◽  
Jianhong Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Head And Neck ◽  
Squamous Cell ◽  
Synergistic Effects ◽  
Tumor Staging ◽  
Drug Effects ◽  
Squamous Cell Carcinomas ◽  
Hpv Status ◽  
Squamous Cancer ◽  
Anatomic Locations

AbstractHead and neck squamous cell carcinomas (HNSCC) induced by human papillomavirus (HPV) have increased recently in the US. However, the distinct alterations of molecules involved in the death pathways and drug effects targeting inhibitor of apoptosis proteins (IAPs) have not been extensively characterized in HPV(+) HNSCC cells. In this study, we observed the distinct genomic and expression alterations of nine genes involved in cell death in 55% HNSCC tissues, which were associated with HPV status, tumor staging, and anatomic locations. Expression of four genes was statistically correlated with copy number variation. A panel of HPV(+) HNSCC lines showed abundant TRAILR2 and IAP1 protein expression, but were not sensitive to IAP inhibitor birinapant alone, while combinatory treatment with TNFα or especially TRAIL enhanced this drug sensitivity. The death agonistic TRAILR2 antibody alone showed no cell inhibitory effects, whereas its combination with birinapant and/or TRAIL protein demonstrated additive or synergistic effects. We observed predominantly late apoptosis mode of cell death after combinatorial treatments, and pan-caspase (ZVAD) and caspase-8 (ZIETD) inhibitors attenuated treatment-induced cell death. Our genomic and expression data-driven study provides a framework for identifying relevant combinatorial therapies targeting death pathways in HPV(+) HNSCC and other squamous cancer types.

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