scholarly journals DNA Methylation and HPV-Associated Head and Neck Cancer

2021 ◽  
Vol 9 (4) ◽  
pp. 801
Author(s):  
Takuya Nakagawa ◽  
Tomoya Kurokawa ◽  
Masato Mima ◽  
Sakiko Imamoto ◽  
Harue Mizokami ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Viral Infections ◽  
The United States ◽  
Hpv Infection ◽  
Pathological Feature ◽  
Aberrant Dna Methylation

Head and neck squamous cell carcinoma (HNSCC), especially oropharyngeal squamous cell carcinoma (OPSCC), has recently been found to be significantly associated with human papillomavirus (HPV) infection. The incidence of OPSCC has been increasing and surpassed the number of cervical cancer cases in the United States. Although HPV-associated OPSCC has a relatively better prognosis than HPV-negative cancer, approximately 20% of HPV-associated HNSCC patients show a poor prognosis or therapeutic response, and the molecular mechanism behind this outcome in the intermediate-risk group is yet to be elucidated. These biological differences between HPV-associated HNSCC and HPV-negative HNSCC are partly explained by the differences in mutation patterns. However, recent reports have revealed that epigenetic dysregulation, such as dysregulated DNA methylation, is a strikingly common pathological feature of human malignancy. Notably, viral infections can induce aberrant DNA methylation, leading to carcinogenesis, and HPV-associated HNSCC cases tend to harbor a higher amount of aberrantly methylated DNA than HPV-negative HNSCC cases. Furthermore, recent comprehensive genome-wide DNA-methylation analyses with large cohorts have revealed that a sub-group of HPV-associated HNSCC correlates with increased DNA methylation. Accordingly, in this review, we provide an overview of the relationship between DNA methylation and HPV-associated HNSCC.

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

All-Cause 30-Day Mortality After Surgical Treatment for Head and Neck Squamous Cell Carcinoma in the United States

2019 ◽  
Vol 42 (7) ◽  
pp. 596-601 ◽  
Author(s):  
Aleksandr R. Bukatko ◽  
Parth B. Patel ◽  
Vindhya Kakarla ◽  
Matthew C. Simpson ◽  
Eric Adjei Boakye ◽  
...  
Keyword(s):  
United States ◽  
Squamous Cell Carcinoma ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
The United States ◽  
Neck Squamous Cell Carcinoma

Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma

2015 ◽  
pp. 123-128 ◽  
Author(s):  
Pedro Henrique Isaacsson Velho ◽  
Gilberto Castro ◽  
Christine H. Chung
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Anticancer Agents ◽  
Neck Region ◽  
Hpv Infection ◽  
Pi3k Pathway ◽  
Neck Squamous Cell Carcinoma ◽  
Preclinical Data

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosal epithelia in the head and neck region. The most common risk factors are tobacco use, alcohol consumption, and HPV infection, particularly in the oropharynx. The HPV-positive HNSCC is biologically and clinically distinct from the HPV-negative HNSCC; however, deregulations within the phosphatidylinositol 3-kinase (PI3K) pathway are frequent in both HPV-positive and HPV-negative HNSCC as it is the most frequently altered oncogenic pathway with a gain-of-function in HNSCC. This article reviews the basic biology and clinical data from the trials involving anticancer agents targeting the PI3K pathway in HNSCC. It also discusses the difficulties of translating the preclinical data to tangible clinical efficacy of these agents in patients with HNSCC even when there is significant preclinical data suggesting the PI3K pathway is a promising therapeutic target in HNSCC. We conclude that additional studies to determine appropriate patient selection for the activation of PI3K pathway and to develop targeted agents either as a monotherapy or combination therapy with favorable toxicity profiles are required before a broader clinical application.

HPV infection in head and neck squamous cell carcinoma

Toukeibu Gan ◽  
2009 ◽  
Vol 35 (4) ◽  
pp. 360-364 ◽  
Author(s):  
Yutaka Tokumaru ◽  
Masato Fujii ◽  
Noboru Habu ◽  
Yoko Yajima ◽  
Tatsuo Matsunaga ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma

Comparison of HPV E6,E7 mRNA/PD-L1 assay using flow cytometry and p16 IHC expression in oral cancer samples.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 114-114 ◽  
Author(s):  
Yvette Carrasco ◽  
Amanda Chargin ◽  
Haitham Mirghani ◽  
Bruce Kendrick Patterson
Keyword(s):  
Flow Cytometry ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Single Cells ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv E6

114 Background: Research into causality of head and neck squamous cell carcinoma (HNSCC) has found a link to HPV infections affiliated with better survival than tobacco associated HNSCC. Currently, p16 immunohistochemistry is used as a predictive biomarker for HPV infection in HNSCC. We were interested in looking at an additional biomarker, HPV E6,E7 mRNA overexpression by flow cytometry, to see if it correlated with p16 status. Each test looks at a different marker of HPV infection, p16 as a surrogate of E7 activity, and E6,E7 mRNA overexpression as a marker of transcriptionally active and integrated virus. Currently p16 positive samples are confirmed with an ISH assay. Additionally, we looked at the PD-L1 expression in these tumors to see if it correlated with HPV mRNA overexpression. Advances in immuno-oncology have brought immunotherapy to the forefront of cancer treatment including HNSCC. Methods: Swabs were collected from Institut Gustave Roussy patients with lesions of the oral pharynx. Swabs were placed into a vial with a proprietary fixation solution and shipped overnight for processing. Upon receipt, samples were passed through a 35 uM filter to remove aggregates. Cells underwent in situ hybridization with E6, E7 mRNA probes (HPV OncoTect), were labeled with PD-L1 Ab, and then stained with a cell cycle dye identify single nucleated cells prior to analysis on the flow cytometer. FFPE biopsy tissue of the lesion was tested with p16 IHC. Positive samples were confirmed by ISH. Results: We analyzed samples from 27 patients with oral cancer with the combined E6, E7 mRNA/PD-L1 assay by flow cytometry and p16/ISH. Concordance between HPV E6,E7 mRNA positive results and p16 positive confirmed by ISH was 74%. Interestingly, PD-L1 expression was seen only in samples without HPV infection (according to HPV E6,E7 mRNA flow result). Samples are still being accrued and updated data will be presented at the meeting. Conclusions: Here we report a novel assay to quantify both HPV E6, E7 mRNA and PD-L1 simultaneously in single cells from head and neck squamous cell carcinoma. In addition, the ability to characterize both E6,E7 mRNA expression and PD-L1 in one test can provide clinicians with insight into treatment options.

Detection of HPV infection in head and neck squamous cell carcinoma: a practical proposal

2013 ◽  
Vol 462 (4) ◽  
pp. 381-389 ◽  
Author(s):  
Johannes H. Dreyer ◽  
Franziska Hauck ◽  
Michelle Oliveira-Silva ◽  
Mario Henrique M. Barros ◽  
Gerald Niedobitek
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Practical Proposal

scholarly journals Unique DNA Methylation Loci Distinguish Anatomic Site and HPV Status in Head and Neck Squamous Cell Carcinoma

2013 ◽  
Vol 19 (19) ◽  
pp. 5444-5455 ◽  
Author(s):  
Roberto A. Lleras ◽  
Richard V. Smith ◽  
Leslie R. Adrien ◽  
Nicolas F. Schlecht ◽  
Robert D. Burk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Anatomic Site ◽  
Hpv Status

scholarly journals Prevalence of Human Papillomavirus Associated with Head and Neck Squamous Cell Carcinoma in Jordanian Patients

2020 ◽  
Vol 14 (1) ◽  
pp. 57-64
Author(s):  
Ashraf I. Khasawneh ◽  
Nisreen Himsawi ◽  
Jumana Abu-Raideh ◽  
Muna Salameh ◽  
Niveen Abdullah ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Human Papillomavirus ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Hpv 16 ◽  
Hpv Dna ◽  
Prophylactic Measures

Background: In addition to smoking and alcohol consumption, human papillomavirus (HPV) is a leading etiology for Head and Neck Squamous Cell Carcinoma (HNSCC). However, this causal association is still understudied in Middle Eastern populations. Objective: The aim of this study was to determine the prevalence of HPV-associated infection in the Jordanian HNSCC patients and the associated HPV genotypes. Methods: Formalin-Fixed Paraffin-Embedded (FFPE) squamous cell carcinoma samples of the head and neck were collected from two referral centers in Amman, Jordan to determine the existence of HPV DNA. After DNA extraction HPV infection and genotyping were identified using real-time PCR. Results: HPV DNA was detected in 19 out of 61 (31.1%) HNSCC samples. Despite screening for 28 different genotypes, HPV 16 was the only genotype identified in all examined samples. Most HPV-positive samples were obtained from the oropharynx (41.7%), oral cavity (37%), and larynx (18.2%). No significant association between HPV 16 genotype and age, sex, tobacco use, anatomical location, or tumor grade was noticed. Conclusion: This study reported a high association between HPV 16 genotype and HNSCC in Jordanian patients. These data should facilitate the implementation of appropriate HPV awareness campaigns, and activate selective prophylactic measures against HPV infection.

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