Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV-positive oropharyngeal squamous cell carcinomas

Ge Gao, Jintu Wang, Jan Kasperbauer, Nicole M. Tombers, Fei Teng, Honglan Gou, Yonggang Zhao, Zhenhong Bao, David I Smith

Research output: Contribution to journalArticle

Abstract

Background: High risk human papillomaviruses (HPV) plays important roles in the development of cervical cancer, a number of other anogenital cancer and they are increasingly found in oropharyngeal squamous cell carcinoma (OPSCC), however there has not been comprehensive analysis about the role how these viruses play in the development of OPSCC. Methods: To characterize the physical status of HPV within OPSCC and to determine the effect this has throughout the host genome, we have performed 30-40X whole genome sequencing (WGS) on the BGI sequencing platform on 34 OPSCCs: 28 of which were HPV positive. We then examined the sequencing data to characterize the HPV copy number and HPV physical status to determine what effect they have on both HPV and human genome structural changes. Results: WGS determined the HPV copy number across the viral genome. HPV copy number ranged from 1 copy to as high as 150 copies in each individual OPSCC. Independent of HPV copy number, most tumors had either a small or a very large deletion in the viral genome. We discovered that these deletions were the result of either HPV integration into the human genome or HPV-HPV sequence junctions. WGS revealed that ~ 70% of these tumors had HPV integrations within the human genome and HPV integration occurred independent of HPV copy number. Individual HPV integrations were found to be highly disruptive resulting in structural variations and copy number changes at or around the integration sites. Conclusions: WGS reveals that there is a great complexity in both HPV sequences present and the HPV integrations events in HPV positive OPSCCs tumors. Thus HPV may be playing different roles in the development of different OPSCCs and this further challenge the HPV-driven carcinogenesis model first proposed for cervical cancer.

Original languageEnglish (US)
Article number352
JournalBMC cancer
Volume19
Issue number1
DOIs
StatePublished - Apr 11 2019

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Squamous Cell Carcinoma
Genome
Human Genome
Viral Genome
Uterine Cervical Neoplasms
Neoplasms

Keywords

  • HPV
  • HPV integration
  • Next generation sequencing
  • OPSCC
  • Whole genome sequencing

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV-positive oropharyngeal squamous cell carcinomas. / Gao, Ge; Wang, Jintu; Kasperbauer, Jan; Tombers, Nicole M.; Teng, Fei; Gou, Honglan; Zhao, Yonggang; Bao, Zhenhong; Smith, David I.

In: BMC cancer, Vol. 19, No. 1, 352, 11.04.2019.

Research output: Contribution to journalArticle

Gao, Ge ; Wang, Jintu ; Kasperbauer, Jan ; Tombers, Nicole M. ; Teng, Fei ; Gou, Honglan ; Zhao, Yonggang ; Bao, Zhenhong ; Smith, David I. / Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV-positive oropharyngeal squamous cell carcinomas. In: BMC cancer. 2019 ; Vol. 19, No. 1.
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abstract = "Background: High risk human papillomaviruses (HPV) plays important roles in the development of cervical cancer, a number of other anogenital cancer and they are increasingly found in oropharyngeal squamous cell carcinoma (OPSCC), however there has not been comprehensive analysis about the role how these viruses play in the development of OPSCC. Methods: To characterize the physical status of HPV within OPSCC and to determine the effect this has throughout the host genome, we have performed 30-40X whole genome sequencing (WGS) on the BGI sequencing platform on 34 OPSCCs: 28 of which were HPV positive. We then examined the sequencing data to characterize the HPV copy number and HPV physical status to determine what effect they have on both HPV and human genome structural changes. Results: WGS determined the HPV copy number across the viral genome. HPV copy number ranged from 1 copy to as high as 150 copies in each individual OPSCC. Independent of HPV copy number, most tumors had either a small or a very large deletion in the viral genome. We discovered that these deletions were the result of either HPV integration into the human genome or HPV-HPV sequence junctions. WGS revealed that ~ 70{\%} of these tumors had HPV integrations within the human genome and HPV integration occurred independent of HPV copy number. Individual HPV integrations were found to be highly disruptive resulting in structural variations and copy number changes at or around the integration sites. Conclusions: WGS reveals that there is a great complexity in both HPV sequences present and the HPV integrations events in HPV positive OPSCCs tumors. Thus HPV may be playing different roles in the development of different OPSCCs and this further challenge the HPV-driven carcinogenesis model first proposed for cervical cancer.",
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AU - Wang, Jintu

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AU - Tombers, Nicole M.

AU - Teng, Fei

AU - Gou, Honglan

AU - Zhao, Yonggang

AU - Bao, Zhenhong

AU - Smith, David I

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AB - Background: High risk human papillomaviruses (HPV) plays important roles in the development of cervical cancer, a number of other anogenital cancer and they are increasingly found in oropharyngeal squamous cell carcinoma (OPSCC), however there has not been comprehensive analysis about the role how these viruses play in the development of OPSCC. Methods: To characterize the physical status of HPV within OPSCC and to determine the effect this has throughout the host genome, we have performed 30-40X whole genome sequencing (WGS) on the BGI sequencing platform on 34 OPSCCs: 28 of which were HPV positive. We then examined the sequencing data to characterize the HPV copy number and HPV physical status to determine what effect they have on both HPV and human genome structural changes. Results: WGS determined the HPV copy number across the viral genome. HPV copy number ranged from 1 copy to as high as 150 copies in each individual OPSCC. Independent of HPV copy number, most tumors had either a small or a very large deletion in the viral genome. We discovered that these deletions were the result of either HPV integration into the human genome or HPV-HPV sequence junctions. WGS revealed that ~ 70% of these tumors had HPV integrations within the human genome and HPV integration occurred independent of HPV copy number. Individual HPV integrations were found to be highly disruptive resulting in structural variations and copy number changes at or around the integration sites. Conclusions: WGS reveals that there is a great complexity in both HPV sequences present and the HPV integrations events in HPV positive OPSCCs tumors. Thus HPV may be playing different roles in the development of different OPSCCs and this further challenge the HPV-driven carcinogenesis model first proposed for cervical cancer.

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