Circulating HPV cDNA in the blood as a reliable biomarker for cervical cancer: A meta-analysis

Abstract

The applications of liquid biopsy have attracted much attention in biomedical research in recent years. Circulating cell-free DNA (cfDNA) in the serum may serve as a unique tumor marker in various types of cancer. Circulating tumor DNA (ctDNA) is a type of serum cfDNA found in patients with cancer and contains abundant information regarding tumor characteristics, highlighting its potential diagnostic value in the clinical setting. However, the diagnostic value of cfDNA as a biomarker, especially circulating HPV DNA (HPV cDNA) in cervical cancer remains unclear. Here, we performed a meta-analysis to evaluate the applications of HPV cDNA as a biomarker in cervical cancer. A systematic literature search was performed using PubMed, Embase, and WANFANG MED ONLINE databases up to March 18, 2019. All literature was analyzed using Meta Disc 1.4 and STATA 14.0 software. Diagnostic measures of accuracy of HPV cDNA in cervical cancer were pooled and investigated. Fifteen studies comprising 684 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.27 (95% confidence interval [CI], 0.24-0.30) and 0.94(95% CI, 0.92-0.96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 6.85 (95% CI, 3.09-15.21) and 0.60 (95% CI, 0.46-0.78), respectively. The diagnostic odds ratio was 15.25 (95% CI, 5.42-42.94), and the area under the summary receiver operating characteristic curve was 0.94 (95% CI, 0.89-0.99). There was no significant publication bias observed. In the included studies, HPV cDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our metaanalysis suggested that detection of HPV cDNA in patients with cervical cancer could be used as a noninvasive early dynamic biomarker of tumors, with high specificity and moderate sensitivity. Further large-scale prospective studies are required to validate the factors that may influence the accuracy of cervical cancer diagnosis and monitoring.

Cell-Free HPV-DNA as a Biomarker for Oropharyngeal Squamous Cell Carcinoma—A Step Towards Personalized Medicine?

“…Another fact that has to be taken into account is that detection of cfHPV-DNA is not specific for a certain location of an HPV-related tumor. Although highly unlikely, the positivity of cfHPV-DNA can also occur due to a simultaneous second HPV-related primary other than oropharynx, as cfHPV-DNA is also reported to be a reliable biomarker for cervical carcinoma [ 39 ].…”

“…Heterogeneity between studies was evaluated through chi-squared and I 2 tests. Values of p < 0.1 or I 2 higher than 50% indicated the existence of significant heterogeneity [ 39 ]. Subgroup analysis was performed to explore the possibility of heterogeneity [ 49 ], whereas publication bias was assessed by Deeks’ funnel plot asymmetry test [ 50 ].…”

Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?

“…HPV 16 and 18 strains have been described as related to high risk, potentially leading to cervical cancer [ 88 ]. A cervical precancerous state is characterised by changes in collar cells making them more susceptible to cervix cancer development within 10-year time span, if not treated in a timely manner [ 89 ]. A meta-analysis study showed that despite the existing heterogeneity amongst studies, HPV cDNA detection is a specific and relatively sensitive tool for cervical cancer diagnosis [ 89 ].…”

“…A cervical precancerous state is characterised by changes in collar cells making them more susceptible to cervix cancer development within 10-year time span, if not treated in a timely manner [ 89 ]. A meta-analysis study showed that despite the existing heterogeneity amongst studies, HPV cDNA detection is a specific and relatively sensitive tool for cervical cancer diagnosis [ 89 ]. Another study revealed the presence of HPV in 98.4% of tumours, being HPV16 and 18 dependent for 89.4% of cervical cancer patients detected [ 87 ].…”

Screening and Identification of New Biomarkers for the Control of Cervical Cancer

“…In CC, methylation of several genes is described and the main examples are DcR1 / DcR2, hTERT, p73, p16, PTEN, E-cadherin, APC, MGMT, FANCF, BRAC1, hMLH1, RASSF1A, DAPK, TSLC1, FHIT, HIC1, RARβ, TIMP2 / TIMP3, CAV-1. As methylation markers, 5-hmC and 5-mC together with 5-foC and 5-caC draw the reversible cycle outline, and 6-mA participates in RNA methylation, especially miRNA (Gu, 2020). The silencing of the epigenetic gene through dense methylation of DNA within the CpG islands occurs in the CC associated with HPV.…”