Molecular mechanisms of human papillomavirus-induced tongue carcinogenesis: A systematic review.

Background: Human papillomavirus (HPV) infection has emerged as a significant etiological factor in tongue cancer, particularly among individuals without conventional risk factors such as tobacco or alcohol use. Understanding the molecular mechanisms underlying HPV-induced tongue carcinogenesis is critical for advancing targeted interventions. Objective: To systematically review existing literature on genetic and epigenetic alterations in HPV-associated tongue cancer, with emphasis on viral oncoprotein interactions, disrupted cellular signalling pathways, and immune evasion mechanisms. Data sources: Electronic databases searched included PubMed, Scopus, Web of Science, Dentistry and Oral Sciences Source, and AMED. Methods: A systematic search using relevant MeSH terms was conducted to identify peer-reviewed studies involving human participants. Duplicates were removed, and studies were screened using the Rayyan software based on predefined inclusion and exclusion criteria. Quality assessment was performed using the Mixed Methods Appraisal Tool (MMAT). Results: The search yielded 3,140 articles, with 27 studies meeting the inclusion criteria after full-text screening and manual search. Quality assessment indicated that 96.3 % of studies (n = 26) had low risk of bias, while one study (3.7 %) had high risk. Key findings showed that HPV E6 and E7 oncoproteins interfere with tumor suppressor pathways (e.g., p53 and Rb), and activate PI3K/Akt, Wnt/β-catenin, and NF-κB signaling. Epigenetic alterations such as promoter hypermethylation, histone modification, and microRNA dysregulation were also implicated. HPV-positive tumours demonstrated immune evasion features. Conclusion: Despite progress in understanding HPV-related tongue carcinogenesis, further research is needed to explore tissue tropism and identify novel therapeutic targets. Prospero id: CRD42024593129.