Can immunohistochemical biomarkers distinguish epithelial dysplasia degrees in actinic cheilitis? A systematic review and meta-analysis

Background: Actinic cheilitis (AC) is a potentially malignant disorder of the lip, characterized by epithelial and connective tissue alterations caused by chronic exposure to ultraviolet radiation. In the past decades, diverse studies have been conducted in lip carcinogenesis and many biomarkers have been identified in lip lesions, yet there is no scientific evidence that determines its usefulness in the clinical setting or in histopathological routine. Therefore, we conducted the first systematic review in this field to summarize the results of published studies on immunohistochemical biomarkers in lip carcinogenesis, to evaluate if there is a marker than can distinguish the different histological grades of AC. Material and Methods: Retrospective studies that investigated immunohistochemical biomarkers in AC defined on standardised histological assessment were gathered from five databases and evaluated. Each study was qualitatively evaluated using the Critical Appraisal Tools from SUMARI. Results: The proliferation marker Ki-67 was the most studied biomarker and we observed, through meta-analysis, that it was differently expressed between AC and lip cancer, but not in AC subgroups. Most articles had a high risk of bias. Conclusions: In summary, the literature lacks quality follow up studies in actinic cheilitis. Multi-centre cohort studies, with patients stratified by treatment type and the use of image analysis software, could be the solution to further address the issues of investigating potentially malignant lesions and help change clinical practice, in terms of individualizing patients' treatment and prognosis prediction.