Molecular biomarkers for early detection and risk profiling of cervical cancer

Cervical cancer(CC) as the fourth most common gynecological malignancy affect half a million women worldwide annually. CC remain a global public health problem due to insufficient screening protocols in developing countries as well as asymptomatic and non-specific nature in the early stages of CC often lead to late-stage diagnosis. Recently early detection of precancerous lesions has undergone dramatic change from cytological testing toward combination of cytology and molecular testing to improve survival rate and making it a treatable malignancy. New generation of molecular diagnostic tests targeting different aspects of CC pathogenesis and increase specificity of screening programs. Today, great efforts have been made to biomarker discovery through analyzing vast data of high throughput omics technologies and machine learning algorithms. The aim of this review is to summarize characterized and well-described biomarkers could be used for timely identification and diagnosis of different stage of cervical cancer and risk categorization. Methods: We searched articles published in English between ۲۰۱۸ and ۲۰۲۴ using keywords from PubMed/ Elsevier /Nature Portfolio journals and Google Scholar database. selected articles are based on biomarkers for primary screening and early detection of Cervical intraepithelial neoplasia ۱,۲,۳ (CIN) Results: based on published data, several molecular biomarkers under clinical investigation proposed for detection of CIN۱,۲,۳. High risk HPV (hrHPV) DNA used as the best test for primary screening, candidate biomarkers for triage test include viral biomarker like hrHPV DNA and genotyping, hrHPV E۶/E۷ mRNA, HPV proteins(E۶, L۱) and cellular biomarker such as TOP۲A/MCM۲ staining, p۱۶/Ki-۶۷ staining and methylation markers in viral or host DNA and other candidate biomarker require more investigation. Conclusion: novel viral and cellular biomarkers are identified to overcome the limitations of current screening programs (lack specificity) and stratifying the HPV+ women who are at the risk of CC progression, manage the clinical decision and added more specificity and sensitivity to screening assays. Regarding HPV implication in a number of other epithelial cancers including anal cancer, head and neck cancers, and even breast cancer, HPV diagnostics are gaining importance in sites other than the cervix. Although theoretically molecular triage of hrHPV+ women could differentiate productive from transforming infection but yet, no molecular triage method could meet the requirement and need further studies.

کلیدواژه ها:

cervical cancer ، biomarker ، early detection ، cervical intraepithelial neoplasia ، human papillomavirus