Asian Pacific Journal of Cancer Prevention, Vol 12, 2011 889 Role of Human Papilloma Virus in Oral Tongue Squamous Cell Carcinoma Asian Pacific J Cancer Prev, 12, 889-896 Introduction Tobacco and alcohol have been attributed as major risk factors for oral squamous cell carcinoma. With the decrease in prevalence of these habits, a parallel reduction in the incidence of head and neck cancer is observed in high risk countries, specifically in sub-sites having strong association with tobacco abuse–larynx and gingivo-buccal carcinoma (Elango 2006). Despite this reduction in overall incidence of head and neck cancer, there is an increase in incidence in certain sub sites such as oropharynx (Shiboski 2005), tongue (Elango 2006) and oral cancer in young adults (Macfarlane 1987). An increasing number of these patients that develop oral and oropharyngeal cancers are without any known local risk factors; implicating etiologic factors other than tobacco and alcohol as its cause. During the past three decades, data supporting human papilloma virus (HPV) as a causative agent in the development and progression of head and neck cancer, particularly that of oropharynx has accumulated. The overall HPV incidence 1 Head and Neck Oncology Service, 2 Department of Molecular Diagnostics, Mazumdar-Shaw Cancer Center, Narayana Hrudayalaya Medical City, Bangalore, 3 Division of Molecular Medicine, Regional Cancer Centre, Thiruvananthapuram, 4 Department of Pathology, 5 Head and Neck Institute, 6 Department of Biostatistics, Amrita Institute of Medical Sciences, Kochi, India *For correspondence: mak12@nyu.edu Abstract Background: Human papilloma virus (HPV) is an important risk factor for head and neck cancer, specifically oropharyngeal cancer, but its association with oral tongue squamous cell carcinoma (SCC) is uncertain. The objectives were to determine the HPV16 prevalence in oral tongue SCCs, its integration status and to correlate the expression of oncogenic proteins with targets. Methods: In this case-control study with oral tongue SCC cases (n=60) and normal oral mucosa (n=46), HPV positivity was determined by polymerase chain reaction (PCR) using consensus and HPV 16 type specific primers and p16 immunohistochemistry (IHC). The viral integration status was determined with primers specific to the E2 gene and in situ hybridization (ISH). Immunohistochemical analysis of HPV oncogenic proteins (E6, E7) and their target proteins (p53, pRb, cyclinD1, p16, Notch-1, EGFR) proteins was carried out in HPV positive cases. The data was analyzed with SPSS software (v 11.0). Survival analysis was carried out by the Kaplan-Meier method. Results: HPV16 was detected in 48% (n=29) of the cases and none of the controls by PCR assay (p<0.001) while p16 IHC, as a surrogate HPV marker, detected 33% (n=18) of the cases; 18% (n=10) were detected by both the methods. Integration was observed in 83% (n=24) by E2-PCR and 67% (n=18) by ISH. The E6-p53 pathway was active in 33% of the cases; E7-pRb in 52% and both in 11%. HPV positivity was associated with well-differentiated cancers (p=0.041) and low recurrence rate (p=0.014). Conclusion: Our study confirms a positive correlation of HPV infection with oral tongue cancer. Keywords: Tongue SCC - HPV - PCR - IHC - carcinogenesis RESEARCH COMMUNICATION Role of Human Papilloma Virus in Oral Tongue Squamous Cell Carcinoma Kalavathy Jayapal Elango 1 , Amritha Suresh 1 , Elango Murugaian Erode 2 , Lakshmi Subhadradevi 3 , Hiran Kattilaparambil Ravindran 4 , Subramania Kulathu Iyer 5 , Sundaram Karimassery Rama Iyer 6 , Moni Abraham Kuriakose 1 * varies depending on tumor location (McKaig 1998; Gillison 2001), the technique employed in the detection of the virus and geographic location of the patients. While two high-risk HPV types 16 and 18 are closely associated with cervical cancer, HPV16 is predominant in head and neck cancers. However, association between oral tongue cancer and HPV has not yet been established. The primary objective of this study was to determine the prevalence of HPV16 in oral tongue cancers. The secondary objectives were to i) identify the HPV integration status, ii) correlate HPV positivity with the expression of HPV oncogenic proteins (E6 and E7) and their target cell cycle regulatory proteins (p53, pRb, p16, cyclinD1, Notch-1, EGFR) Materials and Methods Cases and Controls Patients diagnosed with histologically confirmed squamous cell carcinoma of the oral tongue were recruited