Bryan, Stacey;
(2022)
Circulating HPV DNA as a Biomarker for Early Invasive Cervical Cancer.
Doctoral thesis (M.D.(Res)), UCL (University College London).
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Abstract
High risk HPV infection is responsible for >99% of cervix cancers. HPV enters epithelial cells and integrates with the host genome, causing viral infection and replication. In persistent infections that lead to cancer, the tumour breaches the basement membrane releasing HPV DNA into the bloodstream. A next generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (HPV cDNA) has been developed and demonstrates 88% sensitivity and 100% specificity in patients with locally advanced cervix cancers undergoing radical chemoradiation. We hypothesise that HPV cDNA is detectable in early invasive cervical cancers but not pre-invasive lesions We recruited two cohorts of patients: those with high-grade CIN and those with early invasive carcinoma of the cervix (1A-1B). A blood sample was taken prior to treatment and again at follow-up. DNA extraction from plasma followed by NGS were used for detection of HPV cDNA. We recruited 52 patients, 40 (77%) with high grade lesions and 12 (23%) with early invasive tumours. None of the patients with pre-invasive lesions were positive for HPV cDNA. Two of the samples from the invasive cancers were found to be stage 2 at follow up and therefore excluded from the results. Of the remaining 10 invasive tumours, 1 (10%) reached the threshold of positivity for HPV cDNA in plasma. Re-calculating the thresholds for positivity did not increase the detection of HPV cDNA. We have confirmed that HPV cDNA is absent in CIN. In early cervical tumours, there was low detection of HPV cDNA. This may be explained by small tumour size, poorer access to lymphatics and the circulation, and therefore little shedding of HPV cDNA in plasma at detectable levels. The detection rate of HPV cDNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies is sub optimal.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D.(Res) |
| Title: | Circulating HPV DNA as a Biomarker for Early Invasive Cervical Cancer |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10149121 |
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