Clinical applications and utility of cell-free DNA-based liquid biopsy analyses in cervical cancer and its precursor lesions

Abstract

Human papilloma virus (HPV) is an infectious carcinogenic agent. Nearly all cervical cancers are positive for one of the high-risk HPV subtypes. Although the introduction of the HPV vaccines in many countries have shown tremendous positive effects on the incidence of both cervical intraepithelial lesions (CIN) and invasive cancer, the large majority of females worldwide are still not vaccinated. Patients with diagnosed high-grade CIN need a lifelong close monitoring of possible relapse or development of invasive cancer. Different blood-based liquid biopsy approaches have shown great promise as an easily obtainable minimally invasive tool for early detection and monitoring of disease. Among the different liquid biopsy approaches the clinical relevance of cell-free DNA (cfDNA) in cervical cancer has been best investigated. In cervical cancer, the DNA fragments can be of both, human as well as viral origin. Thus, the mutation and methylation status of genes related to carcinogenesis as well as the HPV status can be analysed in plasma from cervical cancer patients. This review describes recent advances in different cfDNA approaches for early detection and monitoring of cervical cancer and its precursor lesions.

Sarcopenic Obesity in Cervical Carcinoma: A Strong and Independent Prognostic Factor beyond the Conventional Predictors (ESTHER Study—AFRAID Project)

“…Furthermore, understanding the dynamics of SO and its response to interventions within the context of LACC treatment could inform the development of predictive models. These models could incorporate SO along with other potential prognostic factors, such as indices of systemic inflammation [ 22 , 23 ], results from functional imaging [ 40 ], radiomic indices [ 41 , 42 , 43 ], and results of liquid biopsies [ 44 , 45 ]. By comprehensively assessing how these factors interact and influence treatment outcomes, we may move closer to achieving more accurate prognostication and personalized treatment strategies for LACC patients.…”

Testing for Human Papillomaviruses in Urine, Blood, and Oral Specimens: an Update for the Laboratory

“…After oropharyngeal cancer, liquid biopsies have been researched most extensively for cervical cancer studies. The targets evaluated have included cHPV DNA, the more common cancer mutations (e.g., PIK3CA), and host and viral methylation targets, including CADM1 and EPB41L3 as recently reviewed by Herbst et al ( 60 ). Most studies in the cervical context have focused on the detection of invasive disease rather than preinvasive disease.…”

“…Circulating DNA can be single or double stranded and is generally secreted into the blood at an early stage of cancer development through mechanisms that include apoptosis or tumor necrosis ( 60 ) ( Fig. 2 ).…”

The roles of NOP56 in cancer and SCA36

“…Currently, there are no studies reporting methods to detect methylation of the NOP56 promoter. However, there are recent studies using liquid biopsy and quantitative methylation-specific PCR analysis to detect circulating tumor DNA and methylation markers ( 65 ).…”