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Group 3 - Evidence Based Dentistry Tutorial 3

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I have posted 2 articles that I believe will better facilitate the remaining steps of the evidence based process.

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Affiliations

¹ The University of Queensland, Faculty of Medicine, Diamantina Institute, Translational Research Institute, Woolloongabba, QLD, Australia.

² Department of Anatomical Pathology, Pathology Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.

³ Southside Clinical Unit, Faculty of Medicine, The University of Queensland, St Lucia, QLD, Australia.

⁴ Department of Otolaryngology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.

Free PMC article

Free PMC article

Affiliations

¹ The University of Queensland, Faculty of Medicine, Diamantina Institute, Translational Research Institute, Woolloongabba, QLD, Australia.

² Department of Anatomical Pathology, Pathology Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.

³ Southside Clinical Unit, Faculty of Medicine, The University of Queensland, St Lucia, QLD, Australia.

⁴ Department of Otolaryngology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia.

Abstract

Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer throughout the developed and developing world. However, the etiology of OCSCC is still unclear. Here, we explored the extent to which tobacco use, Human Papillomavirus (HPV) infection and genetic and transcriptomic changes contributed to the oncogenesis of OCSCC. In a prospective observational study, we analysed fresh tissue biopsies from 45 OCSCC collected from 51 subjects presenting with OCSCC to the Brisbane Head and Neck Clinics between 2013 and 2015. Exploration of the genetic and transcriptomic landscape of the biopsies were performed using RNA sequencing (RNA-seq) and whole exome sequencing. HPV associated tumours were determined using p16 staining of histological sections and RNA sequencing. Patient demographics including tumor location within the oral cavity, and history of tobacco and alcohol use were correlated with genomic and transcriptomics analyses. About 4.5% of OCSCC were HPV associated. The most frequent mutations in the OCSCC samples were in the TP53 and CDKN2A genes, but no association of specific mutations with HPV or tobacco use was observed. Using weighted gene co-expression network analysis to explore the RNA-seq data, tumors from participants with a history of tobacco use showed a significant trend towards increased mammalian target of Rapamycin (mTOR) signaling and decreased mitochondrial respiration. In conclusion, HPV was shown to be an uncommon association with OCSCC and changes in TP53 transcriptional regulation, mTOR signaling and mitochondrial function were associated with a history of tobacco use. Larger data sets will be required to enable detection of differences which may help with development of personalized therapeutics in the future.

Conflict of interest statement

The authors have declared that no competing interests exist.

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Grant support

This work is supported by project grant funding to IHF and CP from the Garnett Passe and Rodnet Williams Memorial Foundation (grant #016867, https://gprwmf.org.au/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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cyclin-dependent kinase inhibitor p16 / genetics*

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high-throughput nucleotide sequencing / methods*

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papillomaviridae / isolation & purification

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tumor suppressor protein p53 / genetics*

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national center for biotechnology information

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Examining the contribution of smoking and HPV towards the etiology of oral cavity squamous cell carcinoma using high-throughput sequencing: A prospective observational study - PubMed

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Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer throughout the developed and developing world. However, the etiology of OCSCC is still unclear. Here, we explored the extent to which tobacco use, Human Papillomavirus (HPV) infection and genetic and transcriptomic ...

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Group 3 - Evidence Based Dentistry - Tutorial 2

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Group 3 - Evidence Based Dentistry - Tutorial One