The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus

Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the abilit...

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Bibliographic Details
Published in:Cancers 2021-05, Vol.13 (10), p.2451
Main Authors: Lefèvre, Anna C., Pallisgaard, Niels, Kronborg, Camilla, Wind, Karen L., Krag, Søren R. P., Spindler, Karen-Lise G.
Format: Article
Language:English
Subjects:
Anus
Biopsy
Blood
Cancer therapies
Cell division
Chemoradiotherapy
Deoxyribonucleic acid
DNA
Genes
Genomes
Human papillomavirus
Medical prognosis
Patients
Pelvis
Plasma
Radiation therapy
Squamous cell carcinoma
Tumors
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Summary:Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13102451