Innovative Screening Approaches, Targeted Therapies, and Team-Based Care Drive Head and Neck Oncology Advances

Targeted therapies and circulating tumor DNA (ctDNA)–based screening approaches are developments to monitor in the head and neck cancer setting, and multidisciplinary collaboration remains essential to preserving patient speech, swallowing, and breathing functions, according to Laurence J. DiNardo, MD, FACS.

“Detection, monitoring, ctDNA, and biologics are where a lot’s happening in the non-surgical realm,” DiNardo said in an interview with OncLive^® in light of World Head and Neck Cancer Day, which is observed annually on July 27.

In the interview, DiNardo discussed the use and limitations of ctDNA in monitoring residual disease in head and neck cancers; advancements in minimally invasive surgery, immunotherapy, and targeted therapies; and the importance of multidisciplinary collaboration in head and neck cancer management.

DiNardo is the Darlene and George P. Emerson, Jr. Professor and chair of the Department of Otolaryngology/Head and Neck Surgery at the Virginia Commonwealth University (VCU) School of Medicine and the VCU Health System in Richmond.

OncLive: How is the role of ctDNA testing evolving in the head and neck cancer field?

DiNardo: Initially, ctDNA had great promise as a marker for residual disease. The enthusiasm has been somewhat tempered, but it’s still useful.^1,2 Initially, it was thought that having a negative one-time ctDNA post-treatment ensured that a patient would be free of tumor, and then maybe held the promise of negating a need for further surveillance, whether through imaging or even a clinical exam.

However, that has not borne out completely, because what we’re finding is that over time, you may not detect [small] amounts of ctDNA, and therefore, later tests may come back positive as the residual tumor progresses. That has put a damper on the enthusiasm for using it. Nevertheless, it’s still helpful, and is useful in monitoring for residual recurrent head and neck cancer.

At VCU we do use ctDNA testing for human papillomavirus (HPV)–related tumors initially to prove that it’s detectable, and then we do follow-ups. One of the drawbacks is that a patient can eventually convert to positive ctDNA when they didn’t have it initially, so that thought of having a single one-time evaluation of ctDNA post-treatment is not borne out. One of the other downsides is that although ctDNA does often present as positive before clinical or imaging studies demonstrate disease, it then puts you in a situation where a patient may come back with ctDNA-positive disease, and you can’t tell them where the disease is. Then, you can’t manage it unless you’re thinking about systemic [treatment like] chemotherapy, a checkpoint inhibitor, or targeted therapy. That also puts you at a bit of a disadvantage.

There are also people who are trying to work through [these drawbacks] in terms of other uses and other assays. They’re looking at assays for HPV-negative head and neck cancers, and it turns out that HPV-negative squamous cell cancers don’t seem to shed as many cells as HPV-positive head and neck cancers. This is where the direction is now, where people are looking closer to the source. We should maybe look for ctDNA in saliva, or even immediately post-operation in the drainage fluid from the drains that are placed. There are still perhaps more uses for ctDNA, but the jury’s still out as to what is the best method is for using it and what its utility is overall.

What surgical and systemic therapy developments are best poised to influence the head and neck cancer treatment paradigm in the near future?

Looking from diagnosis and surveillance to treatment, surgically, we continue to advance in terms of minimally invasive robotic surgery and free flap reconstruction.

From the oncology standpoint, [there are] biologics. Whether you’re talking about immunotherapy in the form of checkpoint inhibitors or targeted therapy [with] monoclonal antibodies, those are now also running through the treatment algorithms for head and neck cancer. A lot of these are based on the genetics of these tumors. For example, PD-L1 [expression] is important [for identifying tumors that might respond to] pembrolizumab [Keytruda], and there are other [agents] targeting EGFR.

We’ve been applying those, and in multiple clinical trials, we are applying those in conjunction with other therapies. You can consider standalone therapy in certain circumstances with a PD-L1–positive tumor. [However, this approach is] not necessarily curative. Durable responses are always the issue in in treating any cancer. [VCU is] part of clinical trials combining some of the conventional therapies—cisplatin, for example—with some of the immune regulators to see if we can enhance the effect. Then, more recently, we’ve seen multiple biologics targeting multiple specific receptors, trying to use a checkpoint inhibitor on 1 part and a checkpoint inhibitor on another part of the presumed pathway to further shut down cancer growth. Eventually, it would be nice to use multiple biologics simultaneously on tumors with certain genomic signatures.

How might the head and neck data that were presented at the 2026 ASCO Annual Meeting further inform the treatment paradigm over the next few months to years?

I am a surgeon, not a [medical] oncologist, but targeted therapies are the things to watch. We’re seeing them in other cancers as well. In pancreatic cancer, there have been some other breakthroughs that hopefully we can build upon.

More than tumor surveillance, for risk assessment in patients, we have the PATHFINDER 2 trial [NCT05155605], which looked for cell-free DNA [cfDNA] in [several] different cancers as a screening method.³ Eventually, that will likely become standard. [When a patient] reaches a certain age, [such as] 50 years, [they may] get a cfDNA test. I personally participated in one of the trials that drew blood and looked for these tumors.

As a surgeon, what is your main message about the importance of multidisciplinary collaboration with medical oncologists, radiation oncologists, and other specialists across head and neck cancer care?

Working at an academic institution where we have collaboration with radiation therapy, hematology, oncology, head and neck surgery, nutrition, pathology, radiology, and speech therapy is extremely impactful and consequential. [Head and neck cancer] not only affects an organ, but also a tremendous number of functions: speech, swallowing, appearance, and breathing. Having a multidisciplinary team is absolutely necessary for covering all those needs and devising the best plan for the patient based on what we expect for response, as well as their desires. Different patients have different desires in terms of what they want or tolerate in terms of treatment, so we try to tailor to those. We also, with the group, try to come up with the most effective treatment based on the multiple ways we attack cancer.

References

1. Izumchenko E, Sloane HS, Edelstein DL, et al. Intrapatient comparative analysis of tumor-informed ctDNA and ctHPV-DNA in patients with HPV-driven OPSCC. J Clin Oncol. 2026;44(suppl 16):6075. doi:10.1200/JCO.2026.44.16_suppl.6075
2. Bola S, Cutts A, Vavoulis D, et al. Pre-treatment circulating tumour DNA (ctDNA) to predict survival and aid decision-making in head and neck cancer patients: 5-year outcome analysis. J Clin Oncol. 2026;44(suppl 16):e18017. doi:10.1200/JCO.2026.44.16_suppl.e18017
3. Giridhar K, McDonnell III CH, Kurbegov D, et al. Safety and performance results from PATHFINDER 2, a registrational study of a multi-cancer early detection (MCED) test in an intended-use population. J Clin Oncol. 2026;44(suppl 16):LBA10509. doi:10.1200/JCO.2026.44.16_suppl.LBA10509