Katharine A. Price, MD, discusses the potential role for injectable HPV-targeted immunotherapy vaccines in HPV16-positive head and neck squamous cell carcinoma.  

Dr Price on the Potential Role for HPV-Targeted Immunotherapy Vaccines in HPV+ HNSCC

Katharine A. Price, MD, associate professor, oncology, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses the potential role for injectable HPV-targeted immunotherapy vaccines for patients with HPV16-positive head and neck squamous cell carcinoma (HNSCC).

Several HPV-targeted vaccines are currently being investigated within the HNSCC treatment space, with the most promising data emerging in the first-line recurrent/metastatic setting in combination with checkpoint inhibitors. Although there are some studies looking at these vaccines in treatment-refractory patients, the response rate in that population tends to be lower, Price states. Ongoing trials are also exploring the use of therapeutic vaccines without immunotherapy, she notes. Based on the trajectory of current trials, it is likely that the first indication for these vaccines will be in patients with recurrent/metastatic disease and a combined positive score (CPS) of 1 or greater, Price speculates.

, patients with a CPS of 20 or higher may derive more benefit from these vaccines, similar to what is observed with immunotherapy, Price reports. Some trials are now restricting enrollment to patients with a CPS of 20 or higher, although the planned phase 3 VERSATILE-003 trial will enroll patients with a CPS of 1 or greater, she notes. However, for patients with PD-L1–negative disease, a treatment gap may still exist with the emergence of these therapeutic vaccines, Price says.

Another interesting area of investigation with therapeutic vaccines is in patients with biochemical or molecular recurrences, Price continues. With the increasing use of circulating tumor DNA (ctDNA) assays in routine practice, more patients are being identified who have rising ctDNA levels after curative-intent treatment but no evidence of disease, she elaborates. In these cases, it is conceivable that therapeutic vaccines could be used to prevent or delay significant recurrence, with ctDNA levels serving as a marker for treatment response, Price states.

As research progresses, therapeutic vaccines are likely to become integrated into various treatment paradigms, including the curative-intent setting. For now, the focus remains on studying these vaccines in the first-line recurrent/metastatic disease space, Price concludes.

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Katharine A. Price, MD, discusses the potential role for injectable HPV-targeted immunotherapy vaccines in HPV16-positive head and neck squamous cell carcinoma.

The clinical learning environment for medical trainees is the foundation of medical training programs. However, discrimination and bias during medical education is a nefarious and pervasive fact of life, particularly for women and under-represented minority groups. Not only are such experiences damaging to the trainee, but they can also adversely affect patient care and the learning environment as a whole. 

Several years ago, at our institution, we both noticed an uptick in discriminatory comments from patients that were directed toward our hematology/oncology Mayo Clinic School of Graduate Medical Education fellows. We both interact regularly with the fellows, so we had the privilege of hearing about these patient encounters firsthand. 

Instead of normalizing the fellows’ experiences, we chose to listen to what was happening in the learning environment, lean in, and be curious about what we were being told. From this choice—the choice to not shy away from difficult issues—the idea for our research study entitled “Assessment of Discrimination, Bias, and Inclusion in a United States Hematology and Oncology Fellowship Program” arose organically.

The qualitative study was an in-depth look at our trainees’ experiences surrounding discrimination, bias, and inclusion. We wanted to understand on a granular level what discrimination or bias they encountered during their clinical training, how those events were handled, whether they were reported, who was perpetrating the discrimina-tion, and how the trainees coped with such experiences. We chose to ask about inclusion, as well, along with what factors of the clinical learning environment were supportive and welcoming, with the idea that a learning environment is the collective result of both the negative and the positive. 

We originally intended to conduct our study as in-person, semistructured interviews, but soon learned that under Title VII and Title IX laws, we would be required to report any gender or personal characteristic discrimination, which could result in our participants being subjected to further investigation. Because we wanted our trainees to be able to speak freely and without fear of retribution, we changed our study design to an anonymous phone interview that was conducted by a qualitative research partner with no interaction or knowledge of the hematology/oncology fellows or the training program. During the interviews, no identifying information from either party was exchanged. This method was highly effective at creating a safe environment for trainees to share their experiences of discrimination, bias, and inclusion.

Several key themes emerged that pertained to discrimination and bias. Many of our fellows from diverse ethnic and racial backgrounds were made to feel unwelcome or “alien at home,” even if they were US citizens. Prior to the publication of our work, the description of feeling “alien at home” had not yet appeared in the body of medical literature surrounding discrimination in medical education. Another related theme was that of trainees who were born outside of the United States being treated as outsiders, even if they had been in the country for much of their lives.

Gender bias toward women was also extremely common. Worse, most trainees did not report these events because of the perception that it would be futile and not result in any substantive changes.

An intuitive but notable finding was that diversity itself begets inclusion. At Mayo Clinic, we have the great fortune of recruiting talented trainees from around the world, and we learned that the presence of people from diverse backgrounds made trainees feel welcome. The inherent diversity of the program combined with other factors created a culture of inclusion, even though 100% of the trainees interviewed either witnessed or experienced discrimination or bias. In a nutshell, the positive experiences outweighed the negative. 

We learned several valuable lessons from this study that can be directly translated into action. Most of the episodes of discrimination were micro-aggressions, which are subtle comments or actions as opposed to overt racism or discrimination. Most of the incidents were not of malicious intent but represent engrained societal percep-tions. In other words, the unconscious biases of patients, and sometimes staff, would manifest in words or actions toward trainees. 

Unconscious bias training has proven effective at highlighting the subcon-scious judgments we all make when we interact with the world. We would advocate that all individuals involved in medical education—ideally including patients—complete an unconscious bias training program. 

We also advocate for bystander or “upstander” training for all medical staff to provide practical tools and approaches for supporting medical trainees who experience discrimination or bias. We cannot prevent such events from occurring, but we can control our reactions and mitigate the impact on trainees’ well-being.

In response to our findings, Mayo Clinic has instituted ongoing efforts to combat discrimination. Dr Warsame conducted a department-wide retreat on diversity and inclusion. We developed an annual anonymous, online learning climate assessment survey within the fellowship program to keep track of the learning environment and the changes that occur over time. 

We have conducted bystander training and rolled out unconscious bias training. We continue to promote our institution’s patient and visitor misconduct policy that provides protection and validation to our trainees and employees who speak out against discriminatory behavior from patients and visitors.

Although we conducted this study at a single fellowship program in 2018, as an organization, Mayo Clinic is applying the lessons learned beyond the hematology/oncology department. We have developed and disseminated institution-wide faculty development education on topics such as uncon-scious bias, microaggressions in the learning envi-ronment, supporting trainees who encounter patient bias, and what to do when a patient refuses care because of factors such as gender, religion, or race.

Mayo Clinic now requires additional bystander intervention training for all employees, residents, and fellows. Furthermore, in 2020, more than 1800 residents and fellows participated in a survey regarding our learning climate. Administrators shared anonymous schoolwide and program-specific results to spur conversations and drive improvement initiatives in other programs and departments.

Perhaps the message we would like to share most is not new, but in our current polarized society, it has never been more important: Talking about sensitive topics is part of the solution, not part of the problem. Identifying and naming a problem does not create an issue or make it a reality but is, instead, the first step in helping to solve it. 

We learned so much about ourselves, our trainees, and our program during this process, and we strongly suggest that each institution and program take the steps to learn more about discrimination, bias, and inclusion, as well as how it affects their medical trainees. Together, we can take steps toward a more equitable and discrimination-free medical education.

Warsame RM, Asiedu GB, Kumbamu A, et al. Assessment of discrimina-tion, bias, and inclusion in a United States hematology and oncology fel-lowship program. 

. 2021;4(11):e2133199. doi: 10.1001/jamanetworkopen.2021.33199

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The clinical learning environment for medical trainees is the foundation of medical training programs.

Katharine A. Price, MD

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