Human Papillomavirus and Head and Neck Squamous Cell Carcinoma: Recent Evidence and Clinical Implications

Over the past 20 years, high-risk human papilloma-virus (HPV) infection has been established as a risk factor for developing head and neck squamous cell carcinoma, independent of tobacco and alcohol use. In particular, HPV is strongly associated with the development of oropharyngeal cancer and a small minority of oral cavity cancers. In this review, we summarize what is currently known about the biology of HPV, the mechanisms by which it effects malignant transformation, and the potential impact of HPV status on the clinical management of persons with head and neck cancer.

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HPV-positive status associated with inflamed immune microenvironment and improved response to anti-PD-1 therapy in head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-019-49771-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 16

Author(s):

Jian Wang ◽

Hao Sun ◽

Qin Zeng ◽

Xue-Jun Guo ◽

Hui Wang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Hpv Infection ◽

Neck Squamous Cell Carcinoma ◽

Integrated Analysis ◽

Immune Microenvironment ◽

Hpv Status

Abstract Chemotherapy and radiotherapy predominantly improve the clinical outcomes of patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC). Whether this superiority goes on when treated with immune checkpoint inhibitors is still unclear. This study sought to determine the predictive value and potential mechanisms of HPV status for the treatment of programmed cell death 1 (PD-1)/ligand 1(PD-L1) inhibitors. We conducted an integrated analysis of the relationships between HPV status and PD-L1, tumor mutation burden (TMB) and inflammation-related immune cells and molecules, based on the analysis of repository databases and resected HNSCC specimens. The pooled analysis of overall survival (OS) and objective response rate (ORR) suggested that HPV-positive patients benefited more from PD-1/PD-L1 inhibitors than HPV-negative patients (OS: hazard ratio (HR) = 0.71, p = 0.02; ORR: 21.9% vs 14.1%, odds ratio (OR) = 1.79, p = 0.01). Analysis of public databases and resected HNSCC specimens revealed that HPV status was independent of PD-L1 expression and TMB in HNSCC. However, HPV infection significantly increased T-cell infiltration, immune effector cell activation and the diversity of T-cell receptors. Notably, HPV-positivity correlated with increased immune cytolytic activity and a T-cell-inflamed gene expression profile. This work provides evidence that HPV status can be used to predict the effectiveness of PD-1 inhibitors in HNSCC, independently of PD-L1 expression and TMB, and probably results from an inflamed immune microenvironment induced by HPV infection.

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Impact of HPV Status and AurkA Phe31Ile Polymorphism on The Response to Cetuximab Treatment of Head and Neck Squamous Cell Carcinoma (HNSCC) Patients

10.21203/rs.3.rs-104557/v1 ◽

2020 ◽

Author(s):

Julia Muth ◽

Andreas Roth ◽

Michael Siegl ◽

Guido Piontek ◽

Rudolf Reiter ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Response Prediction ◽

Hpv Infection ◽

Neck Squamous Cell Carcinoma ◽

Hpv Status

Abstract Background: Since 2004, the use of the monoclonal antibody cetuximab has been preferred over platinum-based therapy for patients with advanced Head and neck squamous cell carcinoma (HNSCC). However, the response rate to the treatment is only around 20%. Currently, no biomarkers have been identified to differentiate potential responders from non-responders to cetuximab therapy.Methods: We evaluated the predictive and prognostic properties of AurkA polymorphism and HPV infection in HNSCC patients treated with cetuximab. Clinical data of 434 patients was collected and tissue was analyzed for AurkA polymorphism using PCR. Immunohistochemistry was used to stain for various markers and their expression levels were scored. Cell culture experiments were performed to complement clinical findings.Results: We demonstrated in vivo as well as in vitro that both AurkA polymorphism and HPV status have predictive and prognostic value. Conclusions: AurkA polymorphism and HPV status could be beneficial for response prediction and therapy optimization for HNSCC patients.

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P160 Frequency and Types of Human Papilloma Virus in Head and Neck Squamous Cell Carcinoma

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.132.8.897-a ◽

2006 ◽

Vol 132 (8) ◽

pp. 897

Author(s):

F. Gallegos-Hernandez ◽

D. Hernandez ◽

E. Paredes ◽

R. Flores ◽

G. Minauro ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papilloma Virus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Papilloma Virus

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

Frontiers in Oncology ◽

10.3389/fonc.2020.582827 ◽

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.

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P16 Expression Independent of Human Papilloma Virus in Egyptian Patients with Head and Neck Squamous Cell Carcinoma: A Retrospective Study

International Journal of Science and Research (IJSR) ◽

10.21275/art20175062 ◽

2017 ◽

Vol 6 (7) ◽

pp. 1502-1509

Keyword(s):

Squamous Cell Carcinoma ◽

Retrospective Study ◽

Human Papilloma Virus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Papilloma Virus ◽

Egyptian Patients ◽

P16 Expression

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PO-080 Prevalence of human papilloma virus and its phylogenetic analysis in patients with head and neck squamous cell carcinoma in pakistan

10.1136/esmoopen-2018-eacr25.608 ◽

2018 ◽

Author(s):

M Kashif ◽

M Sadia ◽

T Romeeza ◽

J Shah ◽

A Nadeem

Keyword(s):

Squamous Cell Carcinoma ◽

Phylogenetic Analysis ◽

Human Papilloma Virus ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Papilloma Virus

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Targeting the PI3K Pathway in Head and Neck Squamous Cell Carcinoma

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2015.35.123 ◽

2015 ◽

pp. 123-128 ◽

Cited By ~ 20

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.

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