Liquid biopsy of HPV DNA in cervical cancer

Cheung, Tak Hong; Yim, So Fan; Yu, Mei; Worley, Michael J.; Fiascone, Stephen; Chiu, Rossa W.̉K.; Lo, KW; Siu, Nelson S.S.; Wong, M.W.T.; Yeung, Albert T.; Wong, R.C.P.; Chen, Zigui; Elias, Kevin M.; Chung, Tony K.H.; Berkowitz, Ross S.; Wong, Yick Fu; Chan, Paul K.S.

doi:10.1016/j.jcv.2019.03.005

Cited by 62 publications

(75 citation statements)

References 19 publications

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“…We found that MSP-PCR and ddPCR were more accurate for detecting ctDNA in patients with cervical cancer than qPCR. In particular, the application of ddPCR in liquid biopsy greatly improves the diagnostic value of ctDNA in cervical cancer [40]. However, statistical regression data showed that all these differences between subgroups were not statistically significant (P > 0.05).…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, liquid biopsy has recently been extensively investigated as a potential new diagnostic technique [34,40].…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, there is a need for a minimally invasive and specific test for disease monitoring, which could be beneficial for patients with cervical cancer. Circulating cfDNA has been widely evaluated using liquid biopsies for detecting cancer, monitoring disease, characterizing drug targets, and uncovering resistance in various tumors [40,[42][43][44].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

C²,

Qiu

et al. 2019

Preprint

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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 in cervical cancer remains unclear. Here, we performed a metaanalysis to evaluate the applications of ctDNA 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 ctDNA in cervical cancer were pooled and 2investigated. Fifteen studies comprising 1109 patients with cervical cancer met our inclusion criteria and were subjected to analysis. The pooled sensitivity and specificity were 0.52 (95% confidence interval [CI], 0.33-0.71) and 0.97 (95% CI, 0.91-0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 16.0 (95% CI, 5.5-46.4) and 0.50 (95% CI, 0.33-0.75), respectively. The diagnostic odds ratio was 32 (95% CI, 10-108), and the area under the summary receiver operating characteristic curve was 0.92 (95% CI, 0.90-0.94). There was no significant publication bias observed. In the included studies, ctDNA showed clear diagnostic value for diagnosing and monitoring cervical cancer. Our metaanalysis suggested that detection of human papilloma virus ctDNA 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.

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Section: Discussionmentioning

confidence: 95%

“…Therefore, liquid biopsy has recently been extensively investigated as a potential new diagnostic technique [34,40].…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

C²,

Qiu

et al. 2019

Preprint

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show abstract

“…With the application of new detection methods, higher sensitivity and specificity had been obtained. In particular, the application of ddPCR in liquid biopsy greatly improves the diagnostic value of HPV cDNA [36]. However, statistical regression data showed that all these differences between subgroups were not statistically significant (P > 0.05).…”

Section: Discussionmentioning

confidence: 97%

“…The proliferation or apoptosis of cervical cancer cells will release ctDNA into the peripheral blood circulation system, including HPV DNA. As one of ctDNAs in cervical cancer, circulating HPV DNA (HPV cDNA) can be widely evaluated using liquid biopsies for detecting cancer and monitoring disease [36]. Many previous meta-analyses have reported that the diagnostic accuracy of quantitative analysis of ctDNA is superior to conventional biomarkers for the diagnosis of several cancers, including ovarian cancer [22], gastric cancer [32], lung cancer [37], and colon cancer [38].…”

Section: Discussionmentioning

confidence: 99%

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

Wan²,

Qiu

et al. 2020

PLoS ONE

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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.

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Circulating cell‐free HPV DNA is a strong marker for disease severity in cervical cancer

Bønløkke,

Steiniche,

Sorensen

et al. 2023

Molecular Oncology

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For cervical cancer (CC), circulating cell‐free HPV DNA (ccfHPV) may establish disease severity. Furthermore, HPV integration has been correlated to viral load and survival. In this study, pre‐treatment plasma from 139 CC cases (50 primary surgery patients, 22 primary surgery+adjuvant oncological therapy patients, and 67 primary oncological therapy patients) was collected (2018–2020). Furthermore, plasma from 25 cervical intraepithelial neoplasia grade 3 (CIN3) patients and 15 healthy women (negative controls) were collected. Two next‐generation sequencing (NGS) panels were used to establish ccfHPV presence and human papillomavirus type 16 (HPV16) integration status. ccfHPV was detected in four primary surgery (8.0%), eight primary surgery+adjuvant oncology (36.4%), and 54 primary oncology (80.6%) patients. For primary oncology patients with HPV16‐related cancer (n=37), more ccfHPVneg than ccfHPVpos patients had HPV16 integration (p=0.04), and, in patients with HPV16 integration (n=13), ccfHPVpos patients had higher disease stages than ccfHPVneg patients (p=0.05). In summary, ccfHPV presence is related to disease severity and may add to the debated Sedlis criteria used for identifying patients for adjuvant oncological therapy. However, ccfHPV detection is influenced by HPV integration status and disease stage, and these factors need to be considered in ccfHPVneg patients.

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Liquid biopsy of HPV DNA in cervical cancer

Cited by 62 publications

References 19 publications

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

Diagnostic value of circulating tumor DNA as an effective biomarker in cervical cancer: a meta-analysis

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

Circulating cell‐free HPV DNA is a strong marker for disease severity in cervical cancer

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