Immune Dysregulation and Viral Persistence in HPV-HIV Coinfection: Oncogenic and Clinical Implications

Human papillomavirus (HPV) associated cancers constitute a major global health concern, particularly among people living with human immunodeficiency virus (HIV). Accumulating evidence suggests that HPV-HIV co-infection substantially increases the risk of genital, cervical, and oral cancers; however, the molecular and immunological mechanisms underlying this association remain incompletely elucidated.

To critically review the current evidence regarding HPV-HIV interactions, focusing on immunological synthesis, translation, clinical implications, and development of a comprehensive prevention strategy for viral persistence and carcinogenesis.

The research methods employed were a narrative review of the literature through the use of major scientific databases such as PubMed, Scopus, and Web of Science, searching for articles up to the end of December 2024. Narrative synthesis of relevant studies on HPV-HIV coinfection, immune dysregulation, viral persistence, and cancer development focused on molecular, immunological, and clinical mechanisms. Limitations of this narrative review are that it may suffer from selection bias and does not include a quantitative meta-analysis.

There is epidemiological evidence that HPV-related genital, cervical, and oral cancers occur earlier, are more aggressive, and are much more common in HIV-infected persons. Specifically, clinical data have shown up to a six-fold increase in HPV persistence and an eighteen-fold increase in risk of infection among people who have low levels of CD4⁺ T-cells. Moreover, the prevalence of oral HPV is 2-6 times greater, reaching up to 32% in HIV positive cohorts and 16% in HIV negative controls. This quantitatively greater burden of persistent high-risk HPV infection is associated with immune dysfunction, which includes the depletion and dysfunction of CD4⁺ T cells and dendritic cells, resulting in impaired mucosal immune surveillance. Persistent HPV infection promotes oncogenic transformation through E6/E7-mediated inactivation of tumor suppressor pathways, including p53 and retinoblastoma protein. Chronic inflammation, epithelial barrier disruption, and altered cytokine signaling further contribute to a pro-oncogenic microenvironment.

HPV-HIV coinfection is a biologically synergistic disease condition, which greatly increases the risk of oral, genital, and cervical cancers. A better understanding of this interaction on a mechanistic basis is crucial for optimizing prevention strategies. For HIV-positive populations, the practical recommendations include increased screening for cervical and anal HPV, strict implementation of HPV vaccination, and monitoring of the oral/oropharyngeal HPV in high-risk groups.