HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that is the result of tobacco and/or alcohol abuse or infection with high-risk Human papillomaviruses. Despite the fact that HPV positive HNSCC cancers form a distinct clinical entity with better treatment outcome, all HNSCC are currently treated uniformly with the same treatment modality. At present, biologic basis of these different outcomes and their therapeutic influence are areas of intense investigation. In this review, we will summarize the molecular basis for this different outcome, novel treatment opportunities and possible biomarkers for HPV positive HNSCC. In particular, the focus will be on several molecular targeted strategies that can improve the chemoradiation response by influencing DNA repair mechanisms.

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Most cited references 71

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Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.

N. Agrawal, M Frederick, C. R. Pickering … (2011)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.

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Head and neck cancer.

Athanassios Argiris, Michalis V. Karamouzis, David Raben … (2008)

Most head and neck cancers are squamous cell carcinomas that develop in the upper aerodigestive epithelium after exposure to carcinogens such as tobacco and alcohol. Human papillomavirus has also been strongly implicated as a causative agent in a subset of these cancers. The complex anatomy and vital physiological role of the tumour-involved structures dictate that the goals of treatment are not only to improve survival outcomes but also to preserve organ function. Major improvements have been accomplished in surgical techniques and radiotherapy delivery. Moreover, systemic therapy including chemotherapy and molecularly targeted agents--namely, the epidermal growth factor receptor inhibitors--has been successfully integrated into potentially curative treatment of locally advanced squamous-cell carcinoma of the head and neck. In deciding which treatment strategy would be suitable for an individual patient, important considerations include expected functional outcomes, ability to tolerate treatment, and comorbid illnesses. The collaboration of many specialties is the key for optimum assessment and decision making. We review the epidemiology, molecular pathogenesis, diagnosis and staging, and the latest multimodal management of squamous cell carcinoma of the head and neck.

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Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States.

Anil Chaturvedi, Eric Engels, William F Anderson … (2008)

To investigate the impact of human papillomavirus (HPV) on the epidemiology of oral squamous cell carcinomas (OSCCs) in the United States, we assessed differences in patient characteristics, incidence, and survival between potentially HPV-related and HPV-unrelated OSCC sites. Data from nine Surveillance, Epidemiology, and End Results program registries (1973 to 2004) were used to classify OSCCs by anatomic site as potentially HPV-related (n = 17,625) or HPV-unrelated (n = 28,144). Joinpoint regression and age-period-cohort models were used to assess incidence trends. Life-table analyses were used to compare 2-year overall survival for HPV-related and HPV-unrelated OSCCs. HPV-related OSCCs were diagnosed at younger ages than HPV-unrelated OSCCs (mean ages at diagnosis, 61.0 and 63.8 years, respectively; P < .001). Incidence increased significantly for HPV-related OSCC from 1973 to 2004 (annual percentage change [APC] = 0.80; P < .001), particularly among white men and at younger ages. By contrast, incidence for HPV-unrelated OSCC was stable through 1982 (APC = 0.82; P = .186) and declined significantly during 1983 to 2004 (APC = -1.85; P < .001). When treated with radiation, improvements in 2-year survival across calendar periods were more pronounced for HPV-related OSCCs (absolute increase in survival from 1973 through 1982 to 1993 through 2004 for localized, regional, and distant stages = 9.9%, 23.1%, and 18.6%, respectively) than HPV-unrelated OSCCs (5.6%, 3.1%, and 9.9%, respectively). During 1993 to 2004, for all stages treated with radiation, patients with HPV-related OSCCs had significantly higher survival rates than those with HPV-unrelated OSCCs. The proportion of OSCCs that are potentially HPV-related increased in the United States from 1973 to 2004, perhaps as a result of changing sexual behaviors. Recent improvements in survival with radiotherapy may be due in part to a shift in the etiology of OSCCs.

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Author and article information

Contributors

Elena Kashuba: Role: Academic Editor

Journal

Journal ID (nlm-ta): Cancers (Basel)

Journal ID (iso-abbrev): Cancers (Basel)

Journal ID (publisher-id): cancers

Title: Cancers

Publisher: MDPI

ISSN (Electronic): 2072-6694

Publication date (Electronic): 29 March 2016

Publication date Collection: April 2016

Volume: 8

Issue: 4

Electronic Location Identifier: 41

Affiliations

[1 ]Laboratory of Experimental Radiotherapy, Department of Oncology, Katholieke Universiteit Leuven (KU Leuven), 3000 Leuven, Belgium; ruveyda.dok@ 123456kuleuven.be

[2 ]Department of Radiation Oncology, Leuven Cancer Institute, University Hospitals Leuven, 3000 Leuven, Belgium

Author notes

[* ]Correspondence: sandra.nuyts@ 123456uzleuven.be ; Tel.: +32-1634-7600, Fax: +32-1634-7623

Article

Publisher ID: cancers-08-00041

DOI: 10.3390/cancers8040041

PMC ID: 4846850

PubMed ID: 27043631

SO-VID: 6bfcbbdc-70de-40b0-94f0-db2e4490d010

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies

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Most cited references 71

Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.

Head and neck cancer.

Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States.

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