Abstract
Context: Early diagnosis of head and neck squamous cell carcinomas (HNSCC) is critical for preventing further disease progression. This study aimed to compare the serum folate and homocysteine levels in patients with HNSCC and healthy controls through a systematic review and subsequent meta-analyses. Evidence Acquisition: The research question was: Is there a difference between serum folate and homocysteine levels (O) of patients with HNSCC (E) compared to healthy controls (C)? To conduct a systematic review, keywords were first identified and then searched in Medline/PubMed, Web of Science, ProQuest, EMBASE, Scopus, and Google Scholar databases within the period from January 2000 to November 2023. The searched studies were screened based on inclusion and exclusion criteria, and after assessing the quality of the selected articles using the Joanna Briggs Institute assessment checklist, 10 articles were finally included in the meta-analysis (nine articles for serum folate and eight for homocysteine). Due to the heterogeneity of studies, meta-analyses were conducted according to the random-effects model. Several meta-analyses were carried out because the selected articles were not uniform regarding smoking habits. Results: Regardless of smoking conditions, the serum folate levels of the HNSCC patients were significantly lower than those of the control groups. Similarly, the serum homocysteine levels were significantly higher in the patient groups compared to the control groups. Conclusions: The meta-analyses in this study showed an association between serum folate and homocysteine levels with HNSCC, indicating their possible use as biomarkers for the early detection of HNSCC.