Candidate biomarkers in the cervical vaginal fluid for the (self-)diagnosis of cervical precancer

Abstract

PurposeDespite improvement in vaccines against human papilloma virus (HPV), the causative agent of cervical cancer, screening women for cervical precancer will remain indispensable in the coming 30–40 years. A simple test that could be performed at home or at a doctor’s practice and that informs the woman whether she is at risk would significantly help make a broader group of patients who aware that they need medical treatment. Cervical vaginal fluid (CVF) is a body fluid that is very well suited for such a test.MethodsNarrative review of cervical (pre)cancer candidate biomarkers from cervicovaginal fluid, is based on a detailed review of the literature. We will also discuss the possibilities that these biomarkers create for the development of a self-test or point-of-care test for cervical (pre)cancer.ResultsSeveral DNA, DNA methylation, miRNA, and protein biomarkers were identified in the cervical vaginal fluid; however, not all of these biomarkers are suited for development of a simple diagnostic assay.ConclusionsProteins, especially alpha-actinin-4, are most suited for development of a simple assay for cervical (pre)cancer. Accuracy of the test could further be improved by combination of several proteins or by combination with a new type of biomarker, e.g., originating from the cervicovaginal microbiome or metabolome.

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

“…Proteomic studies have been performed on cervicovaginal fluid to analyze and understand the role of the microbiota on the cervical region metabolism [87][88][89]. A study using proteomic data showed that dysbiosis causes cervicovaginal inflammation and detrimental changes within the mucosal barrier [90].…”

DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

“…α-actinin-4 might play a significant role in the detection of cervical cancer from cervical vaginal fluid. Although this method requires significant improvement, it provides an exciting prospect for the early diagnosis of cervical cancer (Van Ostade et al, 2018). Snoek et al (2019a) have demonstrated that collecting urine is more convenient and comfortable for patients than cervical scrapes and is a promising alternative testing material to screen for cervical cancer.…”

Label‐free cervicovaginal fluid proteome profiling reflects the cervix neoplastic transformation

“…Systems biology makes it possible to approach the task of searching for biomarkers of cervical neoplasia development more comprehensively. Postgenomic methods, including proteomics, are widely used for biomarker discovery in different biofluids: blood, cervicovaginal fluid (CVF), cerebrospinal fluid, peritoneal fluid, saline, urine, and etc . In oncology, protein/peptide panels were proposed for diagnosis of ovarian cancer, breast cancer, lung cancer, and etc.…”

“…CVF proteome was shown to change in different genital tract diseases (bacterial vaginosis, vaginitis, cervicitis, premature rupture of membranes, and neoplastic changes of cervix) . Alpha‐actinin‐4, pyruvate kinase M1/M2 isozyme, and S100A9 were proposed as promising markers of the cervix malignant process . Thus, CVF demonstrates a high potential for the search for biomarkers of the HPV‐associated cervical transformation, risk of disease progression, treatment monitoring, and new therapeutic targets .…”

“…Alpha‐actinin‐4, pyruvate kinase M1/M2 isozyme, and S100A9 were proposed as promising markers of the cervix malignant process . Thus, CVF demonstrates a high potential for the search for biomarkers of the HPV‐associated cervical transformation, risk of disease progression, treatment monitoring, and new therapeutic targets . Further research is necessary to characterize CVF proteome changes during different stages of the cervix neoplastic transformation and associated oncogenic pathways for targeted therapy.…”