bioRxiv preprint first posted online Oct. 22, 2016; doi: http://dx.doi.org/10.1101/082651. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
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High-risk human papillomavirus in oral cavity squamous cell carcinoma
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Vinayak Palve1, Jamir Bagwan1, Neeraja M Krishnan1, Manisha Pareek1, Udita Chandola1, Amritha
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Suresh2, Gangotri Siddappa2, Bonney L James2, Vikram Kekatpure3, Moni Abraham Kuriakose 2,3
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and Binay Panda1*
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India
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Mazumdar Shaw Centre for Translational Cancer Research, Bangalore, India
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Mazumdar Shaw Medical Centre, Bangalore, India
Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, Bangalore,
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*corresponding author:Binay Panda, Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and
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Applied Biotechnology, Bangalore, India, Telephone: +91-9663311188, Email:
[email protected]
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Research support: Department of Electronics and Information Technology, Government of India
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(Ref No: 18(4)/2010-E-Infra., 31-03-2010) and Department of IT, BT and ST, Government of
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Karnataka, India (Ref No: 3451-00-090-2-22).
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Running Head: HPV in oral cavity tumors.
bioRxiv preprint first posted online Oct. 22, 2016; doi: http://dx.doi.org/10.1101/082651. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
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ABSTRACT
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Purpose: The prevalence of human papillomavirus (HPV) in oral cavity squamous cell carcinoma
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(OSCC) varies significantly based on assay sensitivity and patient geography. Accurate detection is
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essential to understand the role of HPV in disease prognosis and management of patients with
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OSCC.
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Methods: We generated and integrated data from multiple analytes (HPV DNA, HPV RNA, and
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p16), assays (immunohistochemistry, PCR, qPCR and digital PCR) and molecular changes (somatic
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mutations and DNA methylation) from 153 OSCC patients to correlate p16 expression, HPV DNA,
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and HPV RNA with HPV incidence and patient survival.
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Results: High prevalence (33-58%) of HPV16/18 DNA did not correlate with the presence of
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transcriptionally active viral genomes (15%) in tumors. Eighteen percent of the tumors were p16
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positive. and only 6% were both HPV DNA and RNA positive. Most tumors with relatively high-
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copy HPV DNA, and/or HPV RNA, but not with HPV DNA alone (irrespective of copy number),
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were wild-type for TP53 and CASP8 genes. In our study, p16 protein, HPV DNA and HPV RNA,
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either alone or in combinations, did not correlate with patient survival. Nine HPV-associated genes
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stratified the virus +ve from the –ve tumor group with high confidence (p
