Germline Variations in Patients With Oral Squamous Cell Carcinoma—Systematic Review

Objective: Integrate studies on germline variations (GV) in patients with oral squamous cell carcinoma (OSCC), aiming to assess the highest frequencies of which genes were altered in patients with this diagnosis. Methods: An electronic search was conducted in four databases and in the gray literature, following the PRISMA 2020 recommendations. Case reports, case series, case–control studies, cross-sectional studies, prospective cohort studies, and retrospective cohort studies reporting GV in patients with OSCC were included for data extraction. Results: Twenty articles were included, covering 146 cases of OSCC. Patients had a mean age of 47.5 years; the majority were male, non-drinkers, and non-smokers. For most cases, p16 staining and human papilloma virus (HPV) status were not investigated/reported. A total of 231 different GV genes were identified in the 146 patients, with the most frequently altered being ND5 (6.1%), CYTB (4.8%), COX1 (4.6%), PDE4DIP (4.1%), ND1 (3.9%), ND4 (3.2%), ND2 (2.7%), ATP6 (2.7%), CDKN2A (2.6%), COX2 (2.4%), COX3 (2.2%), and ND3 and ND6, both accounting for 2% each. Conclusion: This review compiles important data on the most frequent GV in patients with OSCC, enabling new understandings of oral carcinogenesis, as well as future directions for prognosis and treatment.