Usefulness of circulating tumor DNA by targeting human papilloma virus-derived sequences as a biomarker in p16-positive oropharyngeal cancer

AbstractIn head and neck cancer, early detection of recurrence after treatment is important. The contemporary development of therapeutic agents have improved the prognosis after recurrence; however, no biomarker has been established for evaluating therapeutic effects or detecting recurrence. Recently, circulating tumor DNA (ctDNA), which comprises DNA derived from tumor cells and exists in the form of cell-free DNA in the blood, has attracted attention as a minimally invasive and repeatable biomarker for detecting cancer. We validated the usefulness of ctDNA of human papilloma virus (HPV)-derived sequences as a biomarker in HPV-related p16-positive oropharyngeal cancer by assessing 25 patients with p16-positive oropharyngeal cancer. Blood samples were collected from each patient at multiple time points during the treatment, and the plasma was preserved. The ctDNA was extracted from the plasma and analyzed using digital polymerase chain reaction. HPV-derived ctDNA was detected in 14 (56%) of the 25 patients. In all the patients, the samples were found to be ctDNA-negative after initial treatment. Cancer recurrence was observed in 2 of the 14 patients; HPV-derived ctDNA was detected at the time of recurrence. Our results indicate that HPV-derived ctDNA can be a prospective biomarker for predicting the recurrence of p16-positive oropharyngeal cancer.

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Human papilloma virus circulating tumor DNA assay predicts treatment response in recurrent/metastatic head and neck squamous cell carcinoma

Oncotarget ◽

10.18632/oncotarget.27992 ◽

2021 ◽

Author(s):

Catherine T. Haring ◽

Chandan Bhambhani ◽

Collin Brummel ◽

Brittany Jewell ◽

Emily Bellile ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Human Papilloma Virus ◽

Cell Carcinoma ◽

Head And Neck ◽

Treatment Response ◽

Squamous Cell ◽

Circulating Tumor Dna ◽

Papilloma Virus ◽

Dna Assay ◽

Tumor Dna

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Measurement of circulating tumor DNA as a cancer biomarker in gastrointestinal malignancies using a novel next-generation sequencing method.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.217 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 217-217

Author(s):

Edward Samuel James ◽

Azeet Narayan ◽

Stacey Stein ◽

Jill Lacy ◽

Abhijit Patel ◽

...

Keyword(s):

Locally Advanced ◽

Circulating Tumor Dna ◽

Cancer Biomarker ◽

Multiple Time ◽

Metastatic Colon Cancer ◽

Next Generation ◽

Gastrointestinal Malignancies ◽

Time Points ◽

Multiple Time Points ◽

Tumor Dna

217 Background: Circulating tumor DNA (ctDNA) holds promise as a highly specific cancer biomarker. The presence of mutant tumor-derived DNA fragments in the blood provides an opportunity to non-invasively assess tumor mutation profiles and to quantify changes in tumor DNA levels over time. Methods: After obtaining informed consent, plasma samples were collected prospectively at multiple time points in a cohort of patients (pts) with various gastrointestinal (GI) malignancies in the locally advanced, metastatic and adjuvant settings. Hotspot regions of genes known to be commonly mutated in GI tumors were amplified by multiplexed PCR, and the resultant amplicons were subjected to next-generation ultra-deep sequencing. Suppression of sequencer and PCR errors allowed mutations to be identified and quantified with a sensitivity of approximately 1 variant in 5,000 molecules. Sample-specific barcoding allowed simultaneous analysis of up to 96 samples. Results: 29 out of 74 available samples from 17 pts were analyzed for the presence of ctDNA. 3 pts had KRAS mutations exclusively. 2 pts had mutations in two of the evaluated genes: KRAS plus PIK3CA and KRAS plus TP53. 2 pts with measurable mutant ctDNA had samples analyzed at multiple time points. One of these patients with locally advanced pancreatic cancer initially had a KRAS G12D mutation which disappeared after treatment with chemo-radiation therapy, but then he developed significantly rising levels of a different KRAS G12L mutation just preceding the diagnosis of liver metastases by imaging. A second pt with metastatic colon cancer had high levels of ctDNA prior to treatment that decreased dramatically after initiation of mFOLFOX and bevacizumab therapy. Conclusions: Our initial analysis indicates that our technique is able to quantify multiple mutations at very low copy numbers accurately in this cohort of pts with GI cancers. Moreover, we were able to monitor changes in mutation type and quantity using this non-invasive “liquid biopsy” approach. Analysis of remaining samples is ongoing, and additional longitudinal data will be presented.

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