Evaluating the Incidence of HPV-Positive/-Negative, According to NCCN Guidelines


In an interview with Targeted Oncology, Jimmy Caudell, MD, PhD, discussed the biggest challenges being faced in the head and neck cancer space.

Jimmy Caudell, MD, PhD

Jimmy Caudell, MD, PhD

In the United States, the overall incidence of human papillomavirus (HPV)-positive oropharynx cancers is increasing whereas the incidence of HPV-negative cancer is decreasing. These rates could be linked with the impacts of smoking and cancer stage in these patients.1

According to the Official Journal of the National Comprehensive Center Network (NCCN) patients with HPV-positive cancers are overall younger in age. However, when looking at HPV-positive oropharynx cancer rates, numbers are increasing among older adults.

Further, the risk of oropharyngeal cancer is increased by the HPV16 infection. HPV16 comprises approximately 90% of all oropharyngeal cancer cases while HPV18, 33, and 35 make up the rest. HPV16 is even more prevalent in patients with oropharyngeal cancer compared with cervical cancer.

The NCCN guidelines for head and neck cancers currently recommend tumor HPV testing in all patients with oropharyngeal cancer. Investigators are also working on multiple clinical trials in this space, including examining treatment deintensification. This active area of research has already shown promising preliminary results.

Ongoing clinical trials in head and neck cancers are evaluating nivolumab (Opdivo) vs chemotherapy, comparing surgical techniques with radio therapeutic interventions, evaluating concurrent systemic therapy vs radiation alone, and more.

Results from the various phase 3 trials are anticipated to further inform NCCN guidelines for this subset of patients with head and neck cancers.

In an interview with Targeted OncologyTM, Jimmy Caudell, MD, PhD, senior member and vice chair for the Clinical Research Department of Radiation Oncology at Moffitt Cancer Center, discussed the biggest challenges being faced in the head and neck cancer space.

Targeted Oncology: What cancer types comprise the NCCN guidelines for head and neck cancers?

Caudell: The NCCN guidelines for head neck cancers includes recommendations for nasopharyngeal cancer, oral cavity cancer, HPV-positive and HPV-negative oropharyngeal cancer, laryngeal cancer, hypopharyngeal, cancer, cancers of the sinus and more. There are many different diseases that comprise and are included in the head neck guidelines.

Can you discuss some recent practice-changing research in this field?

The biggest change that we've made over the past year is with induction, systemic therapy for locally regionally advanced nasopharyngeal cancers. Recent trials from Southeast Asia have returned as positive. Then of course, integration of immunotherapies in the metastatic setting for a variety of the head and neck cancers, particularly needed pharyngeal cancer and other head and neck cancers.

Can you discuss the overall incidence of HPV-positive and negative or oropharyngeal cancers in the United States?

Overall, the incidence of oropharyngeal cancer is relatively stable, but within the incidence of HPV-positive oropharyngeal cancer, it is increasing quite rapidly, whereas HPV-negative, at least in the United States, is decreasing. Recent publications released in the last 5-10 years consider HPV-related oropharyngeal cancer to be an epidemic.

Like many other smoking-related cancers, HPV-negative cancers of the head and neck have been decreasing because people have been smoking less or not smoking at all. HPV-positive oropharyngeal cancer is increasing in incidence because, at the base of it, it is a sexually transmitted disease.

What ongoing trials are adding to or changing guidelines in this space?

There are multiple trials that are ongoing. Currently, NRG-HN005 [NCT03952585] is comparing nivolumab, which is an immunotherapy agent, with cisplatin [in HPV-positive oropharyngeal cancer]. That's almost completed as a phase 2 component will be moving on, hopefully to phase 3 soon.

There are some other phase 3 trials ongoing which are comparing surgical techniques or surgical interventions to radio therapeutic interventions, as well as in the postoperative setting, looking at the need for concurrent systemic therapy vs just radiation alone. In the nasopharyngeal cancer space, there's a lot of interest, both in escalation as well as de-escalation. Some recent trials have been carried out looking at using plasma EBV as a biomarker, to say, if the EBV level is low in the plasma, therefore, we can do radiation alone vs radiation and chemotherapy.

In the more high-risk setting, I spoke about some of the phase 3 trials that added induction chemotherapy to standard radiation and chemotherapy as being positive, but unfortunately, there were a couple of phase 3 trials that were negative that tried to add immunotherapy to radiation and cisplatin.

What unmet medical needs still exist in the head and neck cancer space?

There have been a lot of different movements in the field. For HPV-positive oropharyngeal cancer, particularly early-stage, there's been a significant focus on de-escalation of therapy. Reducing the amount of radiation, reducing, or changing systemic therapy, using or not using surgical techniques such as transoral robotic surgical techniques. Significant interest has been in multiple phase 3 randomized studies which are ongoing. Interesting phase 2 studies have come out in the space but has been nothing that would change practice right now.

On the other hand, for head neck cancers that are smoking-related, there's still a significant need for intensification of therapy and improving outcomes because the outcomes continue to be less than ideal. Then of course in the metastatic setting, particularly for the PD-L1-positive tumors, immunotherapy has become standard of care. But for patients that progress following immunotherapy or that have low immunogenic scores, CPS less than 1, etc, there continues to be a need for improvements.

What excites you the most for the future of this space?

As a radiation oncologist, what is interesting to me are new radiosensitizers and radioenhancers that can be used in combination with radiation, using radiation to modulate the tumor immune microenvironment. Then, using biomarkers to guide radiation dosing.

Caudell JJ, Gillison ML, Maghami E, et al. NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022: Featured Updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2022;20(3):224-234. doi:10.6004/jnccn.2022.0016
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