Atypical metastases highlight the true potential of ctDNA liquid biopsies for cancer monitoring

Zhao, Brian; Naegele, Saskia; Efthymiou, Vasileios; Hirayama, Shun; Mendel, Jameson T.; Lin, Derrick T.; Das, Dipon; Faden, Daniel L.

doi:10.1016/j.oraloncology.2023.106464

Cited by 1 publication

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“…Detection of HPV cfDNA in blood plasma can identify OPC patients with high sensitivity and specificity ( 11 ) and has been successfully used for diagnosis, prediction of recurrence, and monitoring therapy response in HPV-driven OPC and other HPV-driven head and neck cancers ( 12 – 16 ). HPV cfDNA presence after intended curative treatment is a highly specific predictor of recurrence, and recurrence has been detected up to 19 months earlier by HPV cfDNA in comparison to standard imaging techniques ( 17 ). Therefore, HPV cfDNA is a promising candidate biomarker for a screening approach due to being minimally invasive and being a highly sensitive and specific biomarker for HPV-driven malignancies ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Quantification of human papillomavirus cell-free DNA from low-volume blood plasma samples by digital PCR

Rosing,

Meier,

Schroeder

et al. 2024

Microbiol Spectr

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The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC. This requires sensitive and specific cfDNA detection as cfDNA levels can be very low. To study the predictive power of pre-diagnostic HPV-cfDNA, archived samples from epidemiological cohorts with limited plasma volume are an important source. To establish a cfDNA detection workflow for low plasma volumes, we compared cfDNA purification methods [MagNA Pure 96 (MP96) and QIAamp ccfDNA/RNA] and digital PCR systems (Biorad QX200 and QIAGEN QIAcuity One). Final assay validation included 65 low-volume plasma samples from oropharyngeal cancer (OPC) patients with defined HPV status stored for 2–9 years. MP96 yielded a 28% higher cfDNA isolation efficiency in comparison to QIAamp. Both digital PCR systems showed comparable analytical sensitivity (6–17 copies for HPV16 and HPV33), but QIAcuity detected both types in the same assay. In the validation set, the assay had 80% sensitivity ( n = 28/35) for HPV16 and HPV33 and a specificity of 97% ( n = 29/30). In samples with ≥750 µL plasma, the sensitivity was 85% ( n = 17/20), while in samples with <750 µL plasma, it was 73% ( n = 11/15). Despite the expected drop in sensitivity with decreased plasma volume, the assay is sensitive and highly specific even in low-volume samples and thus suited for studies exploring HPV-cfDNA as an early HPV-OPC detection marker in low-volume archival material. IMPORTANCE HPV-OPC has a favorable prognosis compared to HPV-negative OPC. However, the majority of tumors is diagnosed after regional spread, thus making intensive treatment necessary. This can cause lasting morbidity with a large impact on quality of life. One potential method to decrease treatment-related morbidity is early detection of the cancer. HPV cfDNA has been successfully used for therapy surveillance and has also been detected in pre-diagnostic samples of HPV-OPC patients. These pre-diagnostic samples are only commonly available from biobanks, which usually only have small volumes of blood plasma available. Hence, we have developed a workflow optimized for small-volume archival samples. With this method, a high sensitivity can be achieved despite sample limitations, making it suitable to conduct further large-scale biobank studies of HPV-cfDNA as a prognostic biomarker for HPV-OPC.

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