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      • Record: found
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      HPV-driven oropharyngeal cancer: current knowledge of molecular biology and mechanisms of carcinogenesis

      review-article
      Author(s): 1 , 2 , 2 ,
      Publication date (Electronic):
      Journal: Cancers of the Head & Neck
      Publisher: BioMed Central
      Keywords: Oropharyngeal cancer, HPV, Etiology, Treatment

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          Abstract

          Understanding of oropharyngeal squamous cell carcinoma has significantly progressed over the last decades, and the concept that this disease can be subdivided into two distinct entities based on human papilloma virus (HPV) status has gained acceptance. To combat the constantly growing epidemic of HPV+ oropharyngeal cancer, further investigation and characterization the unique features of the disease, along with the development and implementation of new, targeted therapies, is crucial. In this review, we summarize the etiology, pathogenesis, diagnosis, treatment, and molecular characteristics of HPV-associated oropharyngeal squamous cell carcinoma.

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          Most cited references58

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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.
          Article 0 comments Cited 610 times – based on 0 reviews     Review now
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            ATM and related protein kinases: safeguarding genome integrity.

            Yosef Shiloh (2003)
            Maintenance of genome stability is essential for avoiding the passage to neoplasia. The DNA-damage response--a cornerstone of genome stability--occurs by a swift transduction of the DNA-damage signal to many cellular pathways. A prime example is the cellular response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn, modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing genetic disorder ataxia-telangiectasia (A-T). Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
            Article 0 comments Cited 507 times – based on 0 reviews     Review now
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              Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.

              M. L. Gillison, W Koch, R B Capone … (2000)
              High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5-9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis. HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%-30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2- 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1-12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05-0.61) and smokers (OR = 0.16; 95% CI = 0.02-1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1-167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01-0. 36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07-0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4- 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4-4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8-2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20-0.88). These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.
              Article 0 comments Cited 413 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Wendell G. Yarbrough:
                ORCID: http://orcid.org/0000-0003-0855-6444
                dell@med.unc.edu , natalia.isaeva@med.uc.edu
                Journal
                Journal ID (nlm-ta): Cancers Head Neck
                Journal ID (iso-abbrev): Cancers Head Neck
                Title: Cancers of the Head & Neck
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2059-7347
                Publication date (Electronic): 29 December 2018
                Publication date PMC-release: 29 December 2018
                Publication date Collection: 2018
                Volume: 3
                Electronic Location Identifier: 12
                Affiliations
                [1 ]ISNI 0000000419368710, GRID grid.47100.32, Department of Surgery, Division of Otolaryngology, , Yale University, ; New Haven, CT USA
                [2 ]ISNI 0000000122483208, GRID grid.10698.36, Department of Otolaryngology/Head and Neck Surgery; Lineberger Cancer Center, , University of North Carolina at Chapel Hill, ; 170 Manning Drive, Campus Box 7070, Chapel Hill, NC 27599 USA
                Author information
                http://orcid.org/0000-0003-0855-6444
                Article
                Publisher ID: 39
                DOI: 10.1186/s41199-018-0039-3
                PMC ID: 6460765
                PubMed ID: 29951282
                SO-VID: 39a3b50c-e44c-412b-9923-7cf3f2fce739
                Copyright © © The Author(s) 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 20 August 2018
                Date accepted : 9 December 2018
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                Keywords: oropharyngeal cancer,hpv,etiology,treatment
                Data availability:
                Keywords: oropharyngeal cancer, hpv, etiology, treatment

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