Human papillomavirus (HPV) status of non-tobacco related squamous cell carcinomas of the lateral tongue

Abstract

Objectives: The human papillomavirus (HPV) is an important cause of some head and neck squamous cell carcinomas (HNSCCs), but its role in cancer of the lateral tongue is debatable. Suspicion of HPV causation is heightened when these lateral tongue carcinomas arise in patients that are young and/or have never smoked. The purpose of this study was to determine the incidence of transcriptionally active high risk HPV in these tumors, with a particular emphasis on non-smoking patients who are often presumed to have HPV-positive tumors.

Methods: We evaluated 78 HNSCCs of the lateral tongue for the presence of HPV using p16 immunohistochemistry and an RNA in situ hybridization assay targeting HPV E6/E7 mRNA. The study population was enriched for patients without traditional risk factors such as smoking and drinking.

Results: P16 overexpression was detected in 9 (11.5%) of 78 cases, but HPV E6/E7 mRNA transcripts were detected in only 1 (1.3%) case (positive predictive value of p16 staining for the presence of transcriptionally active HPV=0.12). HPV mRNA transcripts were not detected in any patient under 40 (n=11), or in patients who had never smoked (n=44), had quit smoking (n=15), and/or were only light consumers of alcohol (n=57).

Conclusions: HPV is not detected in the vast majority of lateral tongue carcinomas. In light of the observation that HPV plays little if any role in the development of these cancers, routine HPV testing is unwarranted , even for patients without traditional risk factors. P16 staining is not a reliable marker for the presence of transcriptionally active HPV at this particular anatomic site.

Keywords: Head and neck cancer; Oral cancer; P16; RNA in situ hybridization; Smoking; Tobacco.

Figure 1

An HPV-related squamous cell carcinoma of the lateral tongue. The tumor demonstrates features of “warty carcinoma” including a thickened surface epithelium with downward extension as broad pushing rete pegs (A, hematoxylin and eosin). The tumor cells exhibit varying degrees of koilocytic atypia including perinuclear halos and wrinkled nuclear contours (B, hematoxylin and eosin). Some of the cells have enlarged and multilobulated nuclei (B, inset). The tumor is strongly p16 positive by immunohistochemistry (C) and high risk HPV positive by RNA in situ hybridization (D).

Figure 2

This keratinizing squamous cell carcinoma (A, hematoxylin and eosin) was HPV negative by in situ hybridization even though it overexpressed p16 (B, p16 immunohistochemistry).