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High-risk human papillomavirus in oral cavity squamous cell carcinoma

Vinayak Palve, Jamir Bagwan, Neeraja M Krishnan, Manisha Pareek, Udita Chandola, Amritha Suresh, Gangotri Siddappa, Bonney L James, Vikram Kekatpure, Moni Abraham Kuriakose, Binay Panda
doi: https://doi.org/10.1101/082651
Vinayak Palve
1Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India
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Jamir Bagwan
1Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India
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Neeraja M Krishnan
1Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India
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Manisha Pareek
1Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India
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Udita Chandola
1Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India
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Amritha Suresh
2Mazumdar Shaw Centre for Translational Cancer Research, Bangalore, India
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Gangotri Siddappa
2Mazumdar Shaw Centre for Translational Cancer Research, Bangalore, India
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Bonney L James
2Mazumdar Shaw Centre for Translational Cancer Research, Bangalore, India
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Vikram Kekatpure
3Mazumdar Shaw Medical Centre, Bangalore, India
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Moni Abraham Kuriakose
2Mazumdar Shaw Centre for Translational Cancer Research, Bangalore, India
3Mazumdar Shaw Medical Centre, Bangalore, India
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Binay Panda
1Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore, India
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  • For correspondence: binay@ganitlabs.in
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ABSTRACT

Purpose The prevalence of human papillomavirus (HPV) in oral cavity squamous cell carcinoma (OSCC) varies significantly based on assay sensitivity and patient geography. Accurate detection is essential to understand the role of HPV in disease prognosis and management of patients with OSCC.

Methods We generated and integrated data from multiple analytes (HPV DNA, HPV RNA, and p16), assays (immunohistochemistry, PCR, qPCR and digital PCR) and molecular changes (somatic mutations and DNA methylation) from 153 OSCC patients to correlate p16 expression, HPV DNA, and HPV RNA with HPV incidence and patient survival.

Results High prevalence (33-58%) of HPV16/18 DNA did not correlate with the presence of transcriptionally active viral genomes (15%) in tumors. Eighteen percent of the tumors were p16 positive. and only 6% were both HPV DNA and RNA positive. Most tumors with relatively high-copy HPV DNA, and/or HPV RNA, but not with HPV DNA alone (irrespective of copy number), were wild-type for TP53 and CASP8 genes. In our study, p16 protein, HPV DNA and HPV RNA, either alone or in combinations, did not correlate with patient survival. Nine HPV-associated genes stratified the virus +ve from the –ve tumor group with high confidence (p<0.008) when HPV DNA copy number and/or HPV RNA were considered to define HPV positivity and not HPV DNA alone irrespective of their copy number (p < 0.2).

Conclusions In OSCC, the presence of both HPV RNA and p16 are rare. HPV DNA alone is not an accurate measure of HPV positivity and therefore not informative. Moreover, HPV DNA, RNA or p16 don’t correlate with outcome.

Footnotes

  • Research support: Department of Electronics and Information Technology, Government of India (Ref No: 18(4)/2010-E-Infra., 31-03-2010) and Department of IT, BT and ST, Government of Karnataka, India (Ref No: 3451-00-090-2-22).

  • ABBREVIATIONS

    HPV
    human papillomavirus
    HNSCC
    head and neck squamous cell carcinoma
    OSCC
    oral cavity squamous cell carcinoma
    IHC
    immunohistochemistry
    PCR
    polymerase chain reaction
    qPCR
    quantitative polymerase chain reaction
    ddPCR
    droplet digital polymerase chain reaction
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Posted March 13, 2018.
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    High-risk human papillomavirus in oral cavity squamous cell carcinoma
    Vinayak Palve, Jamir Bagwan, Neeraja M Krishnan, Manisha Pareek, Udita Chandola, Amritha Suresh, Gangotri Siddappa, Bonney L James, Vikram Kekatpure, Moni Abraham Kuriakose, Binay Panda
    bioRxiv 082651; doi: https://doi.org/10.1101/082651
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    High-risk human papillomavirus in oral cavity squamous cell carcinoma
    Vinayak Palve, Jamir Bagwan, Neeraja M Krishnan, Manisha Pareek, Udita Chandola, Amritha Suresh, Gangotri Siddappa, Bonney L James, Vikram Kekatpure, Moni Abraham Kuriakose, Binay Panda
    bioRxiv 082651; doi: https://doi.org/10.1101/082651

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