Abstract

ObjectivesThe presence of and the causative role of high‐risk human papilloma virus (HPV) is a subject of controversy in oral squamous cell carcinoma (OSCC). The disagreement can be related to the misclassification of OSCC as oropharyngeal squamous cell carcinoma and/or lack of standard detection methods. This study aimed to examine the presence of transcriptionally active high‐risk HPV in a homogenous Norwegian cohort of primary and second primary OSCC of the mobile tongue (oral tongue squamous cell carcinoma—OTSCC).MethodsTissue microarrays containing formalin‐fixed and paraffin‐embedded cores of 146 OTSCC from the anterior 2/3 of the tongue (n = 128 primary and n = 18 second primary) from a multicentric Norwegian cohort were examined for the presence of high‐risk HPV by DNA‐ and RNA‐in situ hybridization (ISH) assays and p16 immunohistochemistry.ResultsTranscriptionally active HPV (E6/E7 mRNA) was not identified in any of the OTSCC specimens. In parallel, no tumors were positive for HPV by DNA ISH. Although, 61 (42%) OTSCC demonstrated p16 positivity with varying staining intensity and subcellular localization, only two cases demonstrated strong and uniform p16‐staining (both cytoplasmic and nuclear) in >70% of cancer cells. The absence of transcriptionally active high‐risk HPV in this cohort of OTSCC indicates that high‐risk HPV is an unlikely causative factor in the present material.

Highlights

  • The oral cavity is considered to be a separate anatomical location from the oropharynx

  • Common site of oral cancer among the patients below 45 years of age (Hussein et al, 2017). This is of great concern since patients with oral tongue squamous cell carcinoma (OTSCC) have a significantly more unfavorable prognosis than those at other oral cavity sites (Rusthoven, Ballonoff, Raben, & Chen, 2008)

  • The pathogenic role of human papilloma virus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) has been well established its role in oral squamous cell carcinoma (OSCC) carcinogenesis is a subject of a controversy

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Summary

| INTRODUCTION

The oral cavity is considered to be a separate anatomical location from the oropharynx. Common site of oral cancer among the patients below 45 years of age (Hussein et al, 2017) This is of great concern since patients with oral tongue squamous cell carcinoma (OTSCC) have a significantly more unfavorable prognosis than those at other oral cavity sites (Rusthoven, Ballonoff, Raben, & Chen, 2008). Only a few studies using relatively limited numbers of OSCC have evaluated the presence of high-risk HPV in OSCC by this technique (Bishop et al, 2012; Lewis Jr et al, 2012; Poling et al, 2014) Their results indicate that high-risk HPV prevalence is very low in OSCC and challenge the view that HPV is a possible etiological factor in OSCC. We compared three different and independent approaches for high-risk HPV detection (E6/E7 mRNA and DNA ISH and p16 IHC) in OTSCC

| MATERIAL AND METHODS
| RESULTS
| DISCUSSION
Findings
| CONCLUSION
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