Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive biomarker for head and neck squamous cell carcinoma.
Birk Olson MD, Vanessa Helou MD, Kevin J. Contrera MD, MPH,and Hilary C. McCrary, MD, MPH, on behalf of the Head and Neck Surgical Oncology Committee
Circulating tumor DNA (ctDNA) is emerging as a serum biomarker in oncology, providing insights into tumor biology, treatment responses, and disease monitoring.1 ctDNA consists of DNA fragments found in the bloodstream, originating from dying native cells or directly from tumors. ctDNA offers advantages over traditional tissue biopsies, particularly for diagnosing tumors in difficult anatomical locations. In head and neck squamous cell carcinoma (HNSCC), ctDNA has shown promise for personalized, noninvasive detection, prognostication, and management of recurrences.2
Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are well-known oncogenic viruses implicated in some head and neck malignancies. With a known target, HPV and EBV ctDNA can be quantified with PCR-based techniques, providing cost savings versus other methods. A valid and reliable biomarker would be a valuable tool as a noninferior replacement to other surveillance modalities, such as PET-CTs. Several phase 2 clinical trials support viral ctDNA as a biomarker, as recently reviewed by Nassar and colleagues.3 Commercially available assays are in development, such as NavDx® (Naveris), but larger, multi-institutional prospective studies are still needed.
Nonviral ctDNA comprises fragments of DNA, distinct from viral sources such as HPV or EBV. An example of nonviral ctDNA would be mutations in the p53 gene that are present in the tumor but not in normal cells. If ctDNA of the mutated p53 is present before treatment but absent after treatment, this would suggest that treatment is successful. Whereas, if the mutated p53 DNA is detected after treatment is complete, this would be a concern for persistent disease. Research on nonviral ctDNA has demonstrated its potential for detecting genetic abnormalities in HNSCC.2 Among the significant findings are certain common genetic alterations, which are prevalent in most nonHPV-related HNSCC.4 Post-treatment, nonviral ctDNA in HNSCC can be useful in detecting residual disease, which has been demonstrated in prospective studies.4
Challenges remain in the development of ctDNA as a biomarker, including variability in diagnostic accuracy, a lack of consensus on the optimal targets, and limited data on clinical outcomes. Although these early questions remain, a serum cancer biomarker has the potential to benefit patients across the spectrum of cancer care, from screening to surveillance. Thoughtful development and implementation of this tool will be critical, including education for community providers and patients, expert consensus statements, and, ultimately, clinical practice guidelines.
April Is Head & Neck Cancer Awareness Month
Each year, more than 55,000 Americans will develop cancer of the head and neck (most of which is preventable), and nearly 13,000 will die from cancer of the head and neck. Head & Neck Cancer Awareness Month, which is led by the Head and Neck Cancer Alliance and supported by the AAO-HNS, is dedicated to promoting awareness of oral, head, and neck cancer. Learn more about hosting a head and neck cancer screening in your community and access other patient information to promote the key message of the campaign that early diagnosis is essential to successful treatment of these types of cancers.
References
Zviran A, Schulman RC, Shah M, et al. Genome-wide cell-free DNA mutational integration enables ultra-sensitive cancer monitoring. Nature Medicine. 2020;26(7):1114-1124. doi:10.1038/s41591-020-0915-3
Brandt A, Thiele B, Schultheiß C, Daetwyler E, Binder M. Circulating Tumor DNA in Head and Neck Squamous Cell Carcinoma. Cancers. 2023;15(7):2051. doi:10.3390/cancers15072051
Nassar SI, Suk A, Nguyen SA, Adilbay D, Pang J, Nathan C-AO. The Role of ctDNA and Liquid Biopsy in the Diagnosis and Monitoring of Head and Neck Cancer: Towards Precision Medicine. Cancers. 2024; 16(18):3129. https://doi.org/10.3390/cancers16183129
Flach S, Howarth K, Hackinger S, et al. Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)—a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma. British Journal of Cancer. 2022;126(8):1186-1195. doi:10.1038/s41416-022-01716-7
