Presence Of Human Papillomavirus And Its Relation To Ki-67and COX-2Expressions In Dentigerous Cyst, Keratocystic Odontogenic Tumor, And Ameloblastoma

Aims:The aim of the current study was to investigate the presence of human papillomavirus (HPV) and its relation to the expressions of Ki-67and COX-2proteins in the odontogenic epithelium of dentigerous cyst, keratocystic odontogenic tumor, and ameloblastoma. Furthermore, the possible relation of COX-2and Ki-67expressions was also analyzed.Methodology:The study consisted of51cases,41samples of the total cases were formalin fixed paraffin embedded (FFPE) samples, retrieved from the archive of Pathology Laboratory, Tongji Hospital, Huazhong University of Science and Technology. The remaining10samples were frozen tissue samples, collected from patients intended maxillofacial surgery at Tongji Hospital, Huazhong University of Science and Technology during the research time. Overall, the study samples were distributed into three odontogenic lesion categories, that are dentigerous cyst (n=16), keratocystic odontogenic tumor (n=18), and ameloblastoma (n=17). Conventional PCR method using SPF1/2consensus primers and immunohistochemical analysis were performed for the detection of HPV-DNA, and HPV-L1capsid protein respectively. Moreover, the expressions of Ki-67and COX-2proteins were analyzed immunohistochemically.Results:HPV-L1protein was detected in25%of dentigerous cysts,66.66%of keratocystic odontogenic tumors, and70.58%of ameloblastomas. The expression of HPV-L1protein was significantly higher in keratocystic odontogenic tumors than in dentigerous cysts (p<0.05), and highly significantly higher in ameloblastomas than that in dentigerous cysts (p<0.01). HPV-DNA was detected in25%of dentigerous cysts,33.33%of keratocystic odontogenic tumors, and41.66% of ameloblastomas. Consequently, Kappa coefficient statistical test showed a moderate agreement (κ=0.478) of immunohistochemical and PCR assays for HPV detection. Ki-67expression was highly significantly more in keratocystic odontogenic tumors than that in dentigerous cysts and ameloblastomas (p<0.01). No statistically significant difference was found in the expression of COX-2among the three studied odontogenic lesions (p>0.05). Keratocystic odontogenic tumors showed positive correlations between HPV (HPV-DNA and HPV-L1protein) and Ki-67and COX-2expressions (p<0.05). Whilst, a positive (p<0.05) and a strongly positive (p<0.01) correlations were found between the expressions of Ki-67and COX-2in dentigerous cysts and ameloblastomas respectively.Conclusions:Active HPV infection, represented by HPV-L1expression, and HPV-DNA were present variably in the odontogenic epithelium of dentigerous cyst, keratocystic odontogenic tumor, and ameloblastoma. Furthermore, HPV was associated with increased proliferation rate and the expression of COX-2in the odontogenic epithelium of keratocystic odontogenic tumor, these relations may contribute to the aggressive clinical behavior and local invasiveness of the keratocystic odontogenic tumor. Finally, COX-2was expressed by the odontogenic epithelial cells of dentigerous cyst, keratocystic odontogenic tumor, and ameloblastoma, and it may contribute to local extensions of dentigerous cyst and ameloblastoma by increasing their odontogenic epithelial cells proliferatlons.