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 meta-analysis 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.

Highlights

  • Human papillomavirus (HPV) is a type of papillomavirus that infects human skin and mucosa squamous epithelial cells

  • 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

  • The pooled diagnostic odd ratio (DOR) was 15.25, which indicated a relatively high accuracy of HPV cDNA in cervical cancer

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Summary

Introduction

Human papillomavirus (HPV) is a type of papillomavirus that infects human skin and mucosa squamous epithelial cells. HPVs are DNA double-stranded spherical small viruses with a diameter of about 55 nm. The HPV genome contains approximately 7900 bases and can be divided into three functional regions [1]. The proteins E6 and E7, encoded by the early genes of HPV, can inhibit the functions of p53 and pRh in normal cervical epithelial cells and cause abnormal proliferation of cancerous cells, resulting in the development of genital warts and atypical proliferation of epithelial cells [2]. The immune system of most patients can eliminate HPV within approximately 9–16 months after infection. Persistent infection by some high-risk HPVs, HPV16 and HPV18, may lead to cervical cancer [3,4,5]

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