We are looking at newer approaches. Surgery, specifically robotic surgery, is being more frequently used for these patients. The idea is that we can clear out most of their disease and then perhaps they can get a lower radiation dose and spare chemotherapy afterwards. We are also looking at the possibility of using only radiation therapy. We know that chemotherapy is necessary for HPV-negative tumors; however, for HPV-positive disease, we may be able to get away with using less or no chemotherapy. There are a lot of clinical trials focusing on that right now.
What challenges have you observed with the HPV vaccination?
I am a strong proponent of vaccination. I have 2 children, and I can tell you as soon as they are old enough I will be dragging them to the pediatrician’s office to get them their shot because this presents a very real opportunity to prevent cancer. It has gotten more press for preventing cervical cancer, but we also believe it will prevent most cases of oropharyngeal cancer related to HPV, as well.
The side effects of the vaccine are pretty mild. A sore arm is the thing complained of most often; however, if you look on the internet, you can see a lot of websites alleging other bad things will happen. The science hasn't really borne that out. Hopefully, the HPV vaccine will put me out of a job and force me to learn something else in 20 years.
Unfortunately, the uptake has been low. Less than 30% of eligible people across the country get the vaccination. More girls than boys get it, but boys need to be vaccinated, too. It protects them not only against oropharyngeal cancer, but against genital warts, and possibly penile and anal cancer.
One of the reasons that this vaccine hasn't been taken up too much is that there is an association of HPV as a sexually transmitted disease. There is a fear that we are giving our children mixed messages by vaccinating them at a young age against a disease that is sexually transmitted. I can understand that complaint, but at the same time I would do everything that I can to protect my children from getting cancer, and I don't think the squeamishness about them one day becoming sexually active should factor into that.
What would you like your main message to be about HPV-related head and neck cancer?
HNSCC is 2 entirely different diseases. Biologically and clinically, HPV-negative squamous cell carcinoma is a very different disease than HPV-positive squamous cell carcinoma. Therefore, clinical trials in the future need to differentiate between them.
For HPV-negative disease, we need to focus on intensifying therapy and trying to get better outcomes. In the recurrent and metastatic setting, we need to focus on targeting things like CDK4/6 and other pathways that are possibly involved in cell cycle regulation.
On the other hand, in the locally advanced setting of HPV-positive disease, we need to focus on de-intensifying therapy and trying to spare patients from toxicities. In the metastatic setting, the focus might be a bit different, as well. Immunotherapy might be even more important for HPV-positive disease. Although it is important for both groups, we may have different opportunities to target pathways, such as PI3K. There is also an opportunity to study therapeutic vaccines in this group.
The biggest thing moving forward is that we need to treat these cancers like the 2 entirely different diseases that they are, and not group them together just because, geographically, they occur in the same areas.