Prevalence of human papillomavirus in squamous cell carcinoma of the tongue Carlos Eduardo Xavier dos Santos Ribeiro da Silva, PhD, a Ismael Dale Cotrim Guerreiro da Silva, PhD, b Artur Cerri, PhD, c and Luc Louis Maurice Weckx, PhD, d Sao Paulo, Brazil FEDERAL UNIVERSITY OF SAO PAULO AND SANTO AMARO UNIVERSITY Oncogenic human papillomaviruses (HPVs) are important agents in the genesis of gynecological cancer, and have also been implied in the genesis of oral cancer. With the purpose of evaluating the relationship between HPV and squamous cell carcinoma (SCC) of the tongue, a case-control study was performed. Fifty white male patients who were smokers and had the histological diagnosis of SCC of the tongue were selected. The control group was composed of 10 matched patients with no clinical evidence of tongue lesions. Polymerase chain reaction (PCR) was used to detect the presence of HPV genome in fresh-frozen tissue specimens from SCC of the tongue margin. Thirty-seven patients (74%) had a positive PCR for oncogenic papillomavirus, and only 1 specimen (10%) of the control group was positive for nononcogenic papillomavirus. Based on the statistical analysis of this study there was a 25.6% higher risk for SCC of the tongue to harbor oncogenic HPV than the healthy control tongue tissue. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;104:497-500) Human papillomavirus (HPV) is a virus of the Papil- lomavirus genus, of the Papovaviridae family, with more than 120 subtypes identified up to the moment, and is composed of a genome of 8000 base pairs of double-stranded DNA forming a complex similar to a chromosome encased by a 55-nm nonenveloped outer capsid protein. 1 The cleavage site of viral DNA circular molecules is specific, that is, it is always cleaved at the same site between E1 and E2 genes. E2 is responsible for repressing transcription of the E6 and E7 viral genes. Once E2 is inactivated by cleavage of the viral molecule, a dysregulated expression of the E6 and E7 genes occurs. 1 The oncogenic potential of the HPV is related to gene products that interact and inactivate cell proteins derived from suppressor genes of p53 and p105-RB and promote degradation of these genes, thus blocking their function. Oncogenicity, among other conditions, will depend directly on the degree of affinity between pro- teins derived from tumor suppressor genes and viral proteins derived from the E6 and E7 genes. 1 Thus, “high-risk” E6 and E7 gene products have a high af- finity for p53 and p105-RB-derived proteins, whereas “low-risk” viral gene– derived products have a low affinity for these proteins. The result of viral penetra- tion is the immortalization of cells in which HPV had integrated. These cells morphologically exhibit abnor- mal mitosis, nuclear pleomorphism, aneuploid DNA content consistent with abnormal chromosome number, and chromosome architectural changes. 1 However, these cells only start to generate tumors when the E6 and E7 transforming genes are exposed to activated cell oncogenes. 1 However, HPV may not operate alone in oncogenesis. In theory, other factors such as the host’s immune status, nutritional deficiency, and cigarette and alcohol consumption operate together favoring and po- tentializing tumor onset. The association of these fac- tors with oncogenic HPV subtypes is extremely impor- tant in the genesis of malignant tumors, since cigarettes and alcohol operate as inducing factors and papilloma- virus operates in the tumor progression phase. In fact, recent evidence suggests that HPV can be present in up to 100% of patients with cervical carci- noma. 2 The different types of HPV are divided into 2 groups depending on their oncogenic potential. HPVs considered nononcogenic are the 6, 11, 42, and 54 subtypes, usually present in verrucous lesions, papillo- mas, and condylomas. 3 The oncogenic subtypes are the 16, 18, 31, 33, 35, 39, 45, 51, 55, 56, 58, 66, and 68, which are frequently found in patients with malignant neoplasms. 3,4 The mere presence of oncogenic HPV may increase the relative potential for the development a Professor of Oral Medicine, Department of Otolaryngology and Head and Neck Surgery, Federal University of Sao Paulo–UNIFESP. b Chief of the Laboratory of Molecular Gynecology, Federal Univer- sity of Sao Paulo–UNIFESP. c Full Professor of Oral Medicine, Santo Amaro University-UNISA. d Full Professor, Chief of the Department of Otolaryngology and Head and Neck Surgery, Federal University of Sao Paulo–UNIFESP. Received for publication Nov 24, 2006; returned for revision Mar 29, 2007; accepted for publication Apr 18, 2007. 1079-2104/$ - see front matter © 2007 Mosby, Inc. All rights reserved. doi:10.1016/j.tripleo.2007.04.028 497