High-risk human papilloma virus was not detected in a Norwegian cohort of oral squamous cell carcinoma of the mobile tongue

Abstract

Objectives: The 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). Methods: Tissue 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. Results: Transcriptionally 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.