Abstract

Background Actinic cheilitis (AC) is a poten-tially 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 histopatho-logical routine. Therefore, we conducted the first systematic review in this field to summarize the results of published studies on immunohistochemical bi-omarkers in lip carcinogenesis, to evaluate if there is a marker than can distin-guish the different histological grades of AC. Material and Methods Retrospective stud-ies 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 sub-groups. 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 soft-ware, could be the solution to further address the issues of investigating poten-tially malignant lesions and help change clinical practice, in terms of individu-alizing patients’ treatment and prognosis prediction. Key words:Lip carcinogenesis, actinic cheilitis, lip cancer, bi-omarkers.

Highlights

  • Lip squamous cell carcinoma (LSCC) represents 2030% of all oral cavity tumors and it deserves a specific attention, especially in its pathogeny, that differs from oral squamous cell carcinoma (OSCC) [1]

  • Thereby, many different immunohistochemical biomarkers have been investigated in oral carcinogenesis and a compilation of these results has been outputted [7]; yet, to our best knowledge, there are no systematic reviews on biomarkers of lip carcinogenesis, and researchers and practioners are still not able to determine which Actinic cheilitis (AC) cases will undergo malignant transformation

  • The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD 42017055294. - Study design We conducted a systematic review of human studies to summarize the results of published studies on immunohistochemical biomarkers in lip carcinogenesis, in order to evaluate if there is a marker than can distinguish the different histological grades of actinic cheilitis (AC). - Search strategy We searched and identified articles of the following bibliographic databases: PubMed, Scopus, Web of Science, ScienceDirect and Scielo

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Summary

Introduction

Lip squamous cell carcinoma (LSCC) represents 2030% of all oral cavity tumors and it deserves a specific attention, especially in its pathogeny, that differs from oral squamous cell carcinoma (OSCC) [1]. Thereby, many different immunohistochemical biomarkers have been investigated in oral carcinogenesis and a compilation of these results has been outputted [7]; yet, to our best knowledge, there are no systematic reviews on biomarkers of lip carcinogenesis, and researchers and practioners are still not able to determine which AC cases will undergo malignant transformation. For this reason, we conducted a systematic review to examine if there is some immunohistochemical biomarker that could be related to the degree of epithelial dysplasia in AC.

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