Aim: This study was carried out with the objective of recognizing the involvement of human papillomavirus (HPV) in conditions of oral squamous cell carcinoma (OSCC) and oral potentially malignant conditions and lesions. Materials and Methods: OSCC samples from thirty patients were collected and thirty paraffin-embedded, oral premalignant specimens were collected. It was decided to use as a negative control samples gingiva from healthy individuals who had no prior history of oral proliferative leukoplakia or OSCC. The samples were then processed using a paraffin-embedded tissue block method. Deoxyribonucleic acid will be extracted from the paraffin-embedded tumor sample of sixty case subjects and tested for the presence of HPV DNA using polymerase chain reaction. Results: In study Group 1, 24 samples were taken from males and 6 from females. In study Group 2, 26 cases were males and 4 were females. In Group 1, 16 cases of moderately differentiated and 14 cases of well differentiated each were present. No case of poorly differentiated were found. There was statistically no significant difference present between male and female when Group 1 and Group 2 was considered. In study Group 1, 0 samples had positive HPV DNA detection, whereas 30 samples had negative HPV DNA detection. In study Group 2, 0 samples had positive HPV DNA detection, whereas 30 samples had negative HPV expression. Conclusion: According to our findings, certain incidences of OSCC may be linked to HPV, however, this was not the case for all of the cancers.