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Oral cancer is the most common cancer that affects people all over the world. Oral squamous cell carcinoma affects about 40 to 50 percent in people of India. Tobacco, alcohol, and smoking are the causes of this condition. In addition, the association of human papilloma virus (HPV) with Oral cancer is being greatly discussed. The high-risk HPV 16 and 18 viruses are considered as the most prevalent causes of oral squamous cell cancer however the link is less well-established in terms of epidemiologic and molecular evidence. The role of vaccination for human papilloma virus in cancer prevention, etio-pathogenesis of transmission of infection and carcinogenesis as well as the limitations of HPV molecular analysis could be a matter of exploration. Oral Squamous Cell Carcinomas linked to Human Papillomavirus have been observed to be radiation sensitive, have better results, and have higher rate of survival.