Human papillomaviruses (HPVs) are high-risk causative factors for HPV infection. This infection does not come alone; it is often seen with co-infection with other viruses and acts as a causative agent for several malignancies. The major purpose of this comprehensive study was to highlight some recent advances in biotechnology associated with HPV infection, including understanding its host interactions and cancerous progression. A systematic research strategy was used to gather data from recent, and the most advanced published electronic sources. The compiled data explain the recent understanding of biology, host–viral interaction cycles, co-infection with other viral diseases, and cellular transformation toward malignancies associated with HPV. In recent years, some vaccination protocols have been introduced in the form of live attenuated, subunit, and DNA-based vaccines. Moreover, some strategies of nanotechnology are being employed to synthesize drugs and vaccines with a whole new approach of plant-based products. The data are immense for the proposed research question, yet the need is to implement modern follow-up screening and modern therapeutics at the clinical level and to conduct wide-scale public awareness to lessen the HPV-related disease burden.