Abstract: Vaccination against human papilloma virus (HPV) prevents HPV infections and HPV - related cancers. Most countries currently use a two - dose HPV vaccination schedule, but a growing number of studies have found potential effectiveness of single - dose HPV vaccine, sparking a debate about the feasibility of switching from a two - dose regimen to a single - dose regimen in the global vaccine community. Given the large global disease burden of cervical cancer and inequality between countries and regions due to the tight HPV vaccine supply, World Health Organization Strategic Advisory Group of Experts on Immunization (SAGE) stated that single - dose schedules provide comparable protection to the two - or three - dose schedules at a relevant meeting in April 2022. In this article, we review current status of HPV vaccination and researches on the single - dose HPV vaccine protection, and analyze the opportunity and challenges for single - dose HPV vaccination strategy in the future.