Molecular markers for cervical cancer screening

Abstract

This review gives an overview of current screening practices for cervical cancer. In the introduction, we will cover approaches of population screening focusing on high-risk Human Papilloma Virus (hrHPV) and the need for a better triage assay. We will further assess the impact of current vaccination programs on screening. Subsequently, the review will cover various technological aspects of nucleic acid-and protein-based biomarker assays. We will then detail different molecular markers in view of their use in triage assays, emphasizing epigenetic and protein markers. Finally, we will place this in the context of cost-effectiveness considerations in view of their implementation in high-as well as in low-to middle-income countries. Introduction: Cervical cancer remains a significant healthcare problem, notably in low-to middle-income countries. While a negative test for hrHPV has a predictive value of more than 99.5%, its positive predictive value is less than 10% for CIN2+ stages. This makes the use of a so-called triage test indispensable for population-based screening to avoid referring women, that are ultimately at low risk of developing cervical cancer, to a gynecologist. This review will give an overview of tests that are based on epigenetic marker panels and protein markers. Areas covered: There is a medical need for molecular markers with a better predictive value to discriminate hrHPV-positive women that are at risk of developing cervical cancer from those that are not. Areas covered are epigenetic and protein markers as well as health economic considerations in view of the fact that most cases of cervical cancer arise in low-to-middle-income countries. Expert opinion: While there are biomarker assays based on changes at the nucleic acid (DNA methylation patterns, miRNAs) and at the protein level, they are not widely used in population screening. Combining nucleic acid-based and protein-based tests could improve the overall specificity for discriminating CIN2+ lesions that carry a low risk of progressing to cervical cancer within the screening interval from those that carry an elevated risk. The challenge is to reduce unnecessary referrals without an undesired increase in false-negative diagnoses resulting in cases of cervical cancer that could have been prevented. A further challenge is to develop tests for low-and middle-income countries, which is critical to reduce the worldwide burden of cervical cancer.

Analysis of the Clinical Value of MAGE-A9 Expressions in Cervical Cancer Tissues and PBMC

“…It is often considered the result of multifactor, multistep, and long-term effects. Infections such as HPV and erefore, related research has attracted much attention [10].…”

“…Exploring sensitive biological markers related to the occurrence and development of cervical cancer can provide early clinical diagnosis and treatment. Therefore, related research has attracted much attention [ 10 ].…”

Point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation for the early detection and treatment of cervical pre-cancer in women in Papua New Guinea: a prospective, single-arm intervention trial (HPV-STAT)

“…18 It is probable that a high proportion of women with cytologically confirmed squamous cell carcinoma and a healthy cervix on examination, who were treated by same-day thermal ablation, could be found to have CIN2 or worse rather than squamous cell carcinoma on histology, but this cannot be known for certain. Newly available and emerging technologies, such as visualisation of cervix by digital colposcopy or deeplearning-based automated visual evaluation, and disease biomarkers 38 (eg, host DNA methylation), could have roles in augmenting future algorithms for HPV-based screening in women from LMICs and in identifying women at greatest risk of invasive disease.…”

Potential clinical utility of plasma D-dimer levels among women with cervical cancer in Lagos, Nigeria

“…Therefore, the search for a more reliable marker of early detection and prognostic monitoring of CC continues. Serum tumour biomarkers have been shown to play several roles in cancer management including early detection through screening, diagnostic confirmation, prognostication, monitoring and response to specific treatments [5]. Activation of clotting is common in cancers; hence, there is a high incidence of thrombosis in metastatic, fast-growing, biologically aggressive cancer [6].…”