Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer

Bailey A. LeConte, Peter Szaniszlo, Susan M. Fennewald, Dianne I. Lou, Suimin Qiu, Nai Wei Chen, John H. Lee, Vicente Resto

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2% versus 52.9%), while HPV18 (1.5% versus 18.2%) and HPV45 (0.7% versus 9.9%) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2% versus 71.4%), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4% versus 22.5%) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60% in 2003 to 80% in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.

Original languageEnglish (US)
Article numbere0203403
JournalPLoS One
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2018

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Oropharyngeal Neoplasms
uterine cervical neoplasms
Papillomaviridae
Viral Genome
Uterine Cervical Neoplasms
Genes
genome
DNA sequences
Asian Americans
Human Genome
Tumors
Tissue
mutation
Mutation
Oropharynx
Mutation Rate
oropharyngeal neoplasms
DNA Sequence Analysis
Cervix Uteri
neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer. / LeConte, Bailey A.; Szaniszlo, Peter; Fennewald, Susan M.; Lou, Dianne I.; Qiu, Suimin; Chen, Nai Wei; Lee, John H.; Resto, Vicente.

In: PLoS One, Vol. 13, No. 8, e0203403, 01.08.2018.

Research output: Contribution to journalArticle

LeConte, BA, Szaniszlo, P, Fennewald, SM, Lou, DI, Qiu, S, Chen, NW, Lee, JH & Resto, V 2018, 'Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer', PLoS One, vol. 13, no. 8, e0203403. https://doi.org/10.1371/journal.pone.0203403
LeConte, Bailey A. ; Szaniszlo, Peter ; Fennewald, Susan M. ; Lou, Dianne I. ; Qiu, Suimin ; Chen, Nai Wei ; Lee, John H. ; Resto, Vicente. / Differences in the viral genome between HPV-positive cervical and oropharyngeal cancer. In: PLoS One. 2018 ; Vol. 13, No. 8.
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abstract = "Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2{\%} versus 52.9{\%}), while HPV18 (1.5{\%} versus 18.2{\%}) and HPV45 (0.7{\%} versus 9.9{\%}) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2{\%} versus 71.4{\%}), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4{\%} versus 22.5{\%}) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60{\%} in 2003 to 80{\%} in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.",
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AB - Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2% versus 52.9%), while HPV18 (1.5% versus 18.2%) and HPV45 (0.7% versus 9.9%) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2% versus 71.4%), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4% versus 22.5%) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60% in 2003 to 80% in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.

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