Prevalence and Expression of Human Papillomavirus in 53 Patients with Oral Tongue Squamous Cell Carcinoma

Background/Aim: Human papillomavirus (HPV) infection has been considered a potential risk factor for the development of oral tongue squamous cell carcinoma (SCC). The purpose of the present study was to investigate HPV infection and high-risk HPV E6/E7 mRNA expression in SCC of the oral tongue in 53 Greek patients. Materials and Methods: Fifty-three biopsies were collected from patients with SCC of the oral tongue and tested for HPV DNA and E6/E7 mRNA expression. Results: The overall prevalence of HPV DNA was 11.3% (6/53), while high-risk HPV DNA was found in 7.5% (4/53) of SCC of the oral tongue. E6/E7 mRNA expression was observed in 9.4% (5/53) samples examined. HPV 16 was the commonest genotype identified by both DNA and RNA assays. A total of 28.3% (15/53) of the patients were non-smokers and nondrinkers. HPV infection was strongly associated with abstinence from tobacco and alcohol (p=0.013). Conclusion: The presence of high-risk HPV E6/E7 mRNA expression suggests that HPV may be implicated in the pathogenesis of SCC of the oral tongue. HPV infection with high-risk (hr) types has an established role in the pathogenesis of a subset of squamous cell carcinoma (SCC) of the oropharynx (1). In contrast, detection rates of hrHPV in SCC of the oral cavity demonstrate a great variability (2, 3), even in young patients (<45 years old) with no exposure to traditional risk factors, such as tobacco usage and alcohol consumption. A notable increase of SCC of the oral cavity in young patients has been reported (4, 5). The majority of HPV-associated SCCs of the oropharynx are characterized by expression of hrHPV-type oncoproteins E6/E7 (6), which de-regulate cell division and differentiation, due to persistent HPV infection and subsequent viral integration. Interestingly, HPV integration and expression of E6/E7 oncogenes is a less common event in SCC of the oral cavity, indicating that other mechanisms may be implicated in malignant transformation of oral mucosa (5, 7, 8). Both the oropharynx and the oral cavity include portions of the tongue as one of their anatomical sites. Indeed, the anterior two-thirds of the tongue or the oral tongue belong to the oral cavity, while the posterior third or the base of tongue is a part of the oropharynx. hrHPV, especially type 16, is frequently detected in SCC of the base of the tongue indicating its predilection to nonkeratinized locations of the oropharynx with inflammatory activity (9). However, the same does not necessarily apply to SCC of the oral tongue, which is the commonest subsite of SCC of the oral cavity. Many investigators have reported HPV infection rates in SCC of the oral tongue ranging from 0% to 100% (9-15). The remarkable difference in HPV prevalence among studies does not allow for firm conclusions to be drawn regarding the role of HPV in the development of SCC of the oral tongue. The purpose of the current study was to investigate HPV infection and hrHPV E6/E7 mRNA expression in patients with SCC of the oral tongue. Materials and Methods Biopsies were collected from 53 patients who subsequently underwent surgical treatment between May 2012 and May 2013 and sent for routine histopathological analysis. A part of the tumorous tissue was kept in liquid storage medium (Thin-Prep PreservCyt Solution; Hologic, Inc. Ltd. West Sussex, UK) in 4 C. All samples had histologically-confirmed, non-metastatic, moderately-to-poorly differentiated (grade II-III) SCC of the oral tongue and were analyzed for the presence of HPV DNA and E6/E7 mRNA. Patients were eligible if they had not received any 1021 Correspondence to: Efstathia Panotopoulou, St. Savvas Regional Anticancer Oncology Hospital of Athens, 171 Alexandras Avenue, 11522 Athens, Greece. E-mail: epanot@tee.gr