Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

Rautava, Jaana; Syrjänen, Stina

doi:10.1007/s12105-012-0367-2

Cited by 127 publications

(149 citation statements)

References 61 publications

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“…Numerous studies have tried to find biomarkers that would foresee tumor behavior and aid in clinical decision-making. Currently, the most reliable biomarkers in use are the presence of human papilloma virus (HPV) and the expression of its surrogate marker p16 in oropharyngeal squamous cell carcinoma (OPSCC) -HPV being the only prognostic marker cited in the 2015 NCCN guidelines [1][2][3]. For HNSCC of other anatomical localizations there are still no good biomarkers in clinical use.…”

Section: Introductionmentioning

confidence: 99%

“…It is thought that the malignant transformation of HPV positive OPSCC tumor is mainly caused by oncoproteins E6 and E7 [1,2]. The unspliced variant of E6 oncoprotein forms a complex with an ubiquitin-protein ligase leading to subsequent degradation of tumor suppressor p53 through its ubiquitination [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…The unspliced variant of E6 oncoprotein forms a complex with an ubiquitin-protein ligase leading to subsequent degradation of tumor suppressor p53 through its ubiquitination [1,2]. E7 oncoproteins inactivate another important tumor suppressor Rb and its associated pocket proteins.…”

Section: Introductionmentioning

confidence: 99%

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Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas

Lundberg

Renkonen

Haglund

et al. 2016

Acta Oto-Laryngologica

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A A 2016 , ' Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas ' Acta Oto- Laryngologica , vol. 136 ,no. 5 , Conclusions BMI-1 is an upstream repressor of tumor suppressor p16 and their inverse expression patterns have been linked with patient survival in OPSCC. In this material only p16 remained a relevant prognostic marker in OPSCC. Objectives HNSCC tumors carry variable phenotypes and clinical outcomes depending on their anatomical location. In OPSCC, expression of tumor suppressor p16 is used as a surrogate marker of HPV infection and has prognostic value. There are no good prognostic biomarkers for HNSCC tumors of other anatomical locations. Aim To study the expression patterns of p16 and BMI-1 in not only oropharyngeal but also oral, hypopharyngeal, and laryngeal squamous cell carcinomas and to clarify their putative connections with clinical parameters, survival, and each other. Method Hospital records on 130 patients (59 OPSCC, 18 OSCC, 20 HPSCC, and 33 LSCC) diagnosed between 1997-2008 at the Helsinki University Hospital, Finland, were reviewed. BMI-1 and p16 expressions were studied by immunohistochemistry. Results Sixty-eight per cent of OPSCC expressed p16 and expression correlated with lower age, lower T-and higher N-category, and with improved OS and DFS. BMI-1 expression was most prevalent in OPSCC and LSCC, but had no clinical correlations. No correlation between p16 and BMI-1 expression was found.ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas

Lundberg

Renkonen

Haglund

et al. 2016

Acta Oto-Laryngologica

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“…Depending on the anatomic site of the tumor, HPV prevalence is estimated at 23-36% (5). HPV-positive HNSCCs form a distinct subset of HNCs that differs from HPV-negative HNSCCs in tumor biology and clinical characteristics, including superior clinical outcomes (6)(7)(8)(9).…”

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confidence: 99%

“…Integration breakpoints often occur in the HPV early genes E1 or E2, disrupting their expression, which leads to the deregulation of negative feedback control of E6 and E7 oncogene expression by the viral regulatory E2 protein. Integrant-derived transcripts are more stable than those derived from episomal viral DNA, and HPV integration has been associated with increased proliferative capacity and selective growth advantage for the affected cells (6,22). Another crucial event frequently associated with HPV integration is genomic instability of the infected cells (23).…”

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confidence: 99%

Characterization of HPV and host genome interactions in primary head and neck cancers

Parfenov¹,

Pedamallu²,

Gehlenborg³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

342

474

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Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twentyfive cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter-and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.cancer | head and neck | papilloma virus | genome rearrangement | integration sites H ead and neck cancer (HNC) is a heterogeneous group of tumors characterized by a common anatomic origin, and most such tumors develop from within the mucosa and are classified as head and neck squamous cell carcinomas (HNSCCs) (1). HNSCC, the sixth most common cancer diagnosed worldwide and the eighth most common cause of cancer death (2), is frequently associated with human papillomavirus (HPV) infection (3, 4). Depending on the anatomic site of the tumor, HPV prevalence is estimated at 23-36% (5). HPV-positive HNSCCs form a distinct subset of HNCs that differs from HPV-negative HNSCCs in tumor biology and clinical characteristics, including superior clinical outcomes (6-9).The molecular pathogenesis of HPV-driven HNSCC also seems distinct from HPV-negative tumors, with previous studies showing a divergent spectrum of alterations in gene expression, mutations, amplifications, and deletions as well as distinct epigenome alterations (10-15). HPV is known to drive tumorigenesis through the actions of its major oncoproteins E6 and E7, which target numerous cellular pathways, including inactivation of p53 and the retinoblastoma (Rb) protein (16-18). Together with E5, they also play an important role in immune evasion, being involved in both innate and adaptive immunity (19,20).Initially after infection, HPV is identified in circular extrachromosomal particles or episomes. A critical step in progression to cancer is the integration of viral DNA into the host cell Significance A significant proportion of head and neck cancer is driven by human papil...

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Finding Pathogenic Nucleic Acid Sequences in Next Generation Sequencing Data

Parfenov

Seidman

2015

CP Human Genetics

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Viruses and bacteria are established as one of the main causes of human diseases from hepatitis to cancer. Recently, the presence of such pathogens has been extensively studied using human whole genome and transcriptome sequencing data. However, detecting and studying pathogens via next generation sequencing data is a challenging task in terms of time and computational resources. In this protocol we give instructions for a simple and quick method to find pathogenic DNA or RNA and detect possible integration of the pathogen genome into the host genome.

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Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

Cited by 127 publications

References 61 publications

Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas

Association of BMI-1 and p16 as prognostic factors for head and neck carcinomas

Characterization of HPV and host genome interactions in primary head and neck cancers

Finding Pathogenic Nucleic Acid Sequences in Next Generation Sequencing Data

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