Human papillomavirus (HPV) infection in the reproductive tract is one of the most prevalent sexually transmitted infections worldwide. Persistent infection with high-risk HPV (HR-HPV) types is a major contributor of cervical cancer and its precancerous lesions. The severity and progression of these lesions are closely linked to multiple HPV infections and viral load. Emerging research indicates that the persistence of HR-HPV infection is influenced not only by viral genetic mutations and trait variations but also by host immune response and genetic factors. Investigations into these risk factors are gaining momentum and hold promise for breakthroughs in the diagnosis and identification of prognostic markers for cervical cancer. This review provides a comprehensive overview of recent advancements in this field.