Circulating HPV DNA as a Biomarker for Pre-Invasive and Early Invasive Cervical Cancer: A Feasibility Study

被引:7
作者
Bryan, Stacey J. [1 ]
Lee, Jen [2 ,3 ]
Gunu, Richard [4 ]
Jones, Allison [4 ]
Olaitan, Adeola [1 ]
Rosenthal, Adam N. [1 ]
Cutts, Ros J. [2 ,3 ]
Garcia-Murillas, Isaac [2 ,3 ]
Turner, Nick [2 ,3 ]
Lalondrelle, Susan [2 ]
Bhide, Shreerang A. [2 ,3 ]
机构
[1] UCL, UCL Elizabeth Garrett Anderson Inst Womens Hlth, Fac Populat Hlth Sci, Med Sch Bldg,74 Huntley St, London WC1E 6AU, England
[2] Inst Canc Res, Fulham Rd, London SW3 6JB, England
[3] Royal Marsden Hosp, Fulham Rd, London SW3 6JJ, England
[4] IfWH, Dept Womens Canc, Translat Res Lab, Ground Floor POGB,72 Huntley St, London WC1E 6DD, England
关键词
human papillomavirus; cervical cancer; next generation sequencing; liquid biopsy; plasma; circulating DNA; HUMAN-PAPILLOMAVIRUS DNA; CELL-FREE; PLASMA; SERUM;
D O I
10.3390/cancers15092590
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN). Methods: Blood samples were collected from patients with CIN (n = 52) and FIGO stage 1A-1B CC (n = 12) prior to treatment and at follow-up. DNA extraction from plasma, followed by NGS, was used for the detection of cHPV-DNA. Results: None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma. Conclusion: Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility.
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页数:11
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