Human papilloma virus (HPV) associated cancers represents a special subgroup of cancers which are potential targets of screening strategy to reduce the burden of HPV-associated cancers. The viruses have different molecular pathways which ultimately lead to the immortalization of cells. The unique pathobiology and detailed discovery of molecular signaling pathways have paved the new dimensions and advancements in both early detection and development of newer treatment strategy in terms sensitivity towards radiotherapy in HPVinduced cancers versus others. Their clinical behavior suggests good prognosis when compared to Non-HPV positive group cancers. The better prognosis between HPV positive and Non-HPV positive cancer demands a timely diagnosis of HPV status to stratify high risk cases to promote personalized management.