BUBR1 expression in benign oral lesions and squamous cell carcinomas: Correlation with human papillomavirus

Abstract

Abstract. Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, an important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also a significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence on BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC, but not in benign oral lesions.

The Role of Human Papillomavirus in Head and Neck Cancers

“…Compared to non-contaminated individuals, the relative risk is 15-to 200-fold in HPV infected patients, and may not show a history of known risk factors for OPC, such tobacco and alcohol consumption, highlighting a different pattern for non-HPV-related OPC (Marur et al, 2008). Moreover, the presence of HPV is also associated to positive cervical lymph nodes of patients in different sites of HNSCCs, but mainly in oropharynx (Goldenberg et al, 2008;Lira et al, 2010;Machado et al, 2010).…”

“…HPV has been found in 4-80% of oral cancers, 15-85% of tonsillar cancers, approximately 24% of non-tumor site-specific HNSCC and 14-57% of OPCs (IARC, 2007;Kreimer et al, 2005;Machado et al, 2010;Syrjanen, 2005;Termine et al, 2008). Brazilian observations in the countryside of Sao Paulo state have found a low prevalence of HPV in tumors of the larynx (Miranda et al, 2009) and an increase in the presence of HPV DNA in oral cavity cancers during the past two decades (Lira et al, 2010;Mazon et al, 2011;Oliveira et al, 2008). The wide variation in HPV prevalence can be attributed to different detection techniques, small sample numbers, differences in the lesions and sampling techniques and epidemiological characteristics of the populations studied (Feller et al, 2010).…”

“…An interesting prevalence profile of the HPV types has been observed in some investigations in the countryside of Sao Paulo state in Brazil, where a higher prevalence of HPV 18 than HPV 16 was found in oral and cervical carcinomas. Furthermore, the presence of HPV 18 was found to be associated with metastasis to the lymph nodes and shorter patient survival Lira et al, 2010;Mazon et al, 2011). …”

The Role of Human Papillomavirus in Pre-Cancerous Lesions and Oral Cancers

“…The HPV prevalence in HNSCC ranges from 3% to 40% and could vary more according to the specific site and HPV has been found in 4-80% of oral squamous cell carcinoma. Brazilian observations in the countryside of São Paulo state have found a low prevalence of HPV in tumors of the larynx [83] and an increase in the presence of HPV-DNA in oral cavity cancers during the past two decades [79][80]84]. The wide variation in HPV prevalence can be attributed to different detection techniques, small sample numbers, differences in the lesions and sampling techniques and epidemiological characteristics of the populations studied [85].…”

“…An interesting prevalence profile of the HPV types has been observed in some investigations in the countryside of Sao Paulo state in Brazil, where a higher prevalence of HPV 18 than HPV 16 was found in oral and cervical carcinomas. Furthermore, the presence of HPV 18 was found to be associated with metastasis to the lymph nodes and shorter patient survival [78][79][80].…”