Treatment of Advanced Head & Neck Squamous Cell Carcinoma - Episode 3
Transcript:Robert Ferris, MD, PhD, FACS: Once we recognized that HPV was a causative factor of oropharyngeal carcinomas, some natural second and third thoughts arose. The first is that the public had to be aware that this was another environmental exposure, and often patients may feel a stigma because they feel that some sort of behavior on their part—perhaps if you think about it from a stigma—that promiscuity, for instance, led to the exposure to HPV.
It should be recognized, however, that we don’t associate any stigma with females, women who have cervical cancer. We would consider that that’s normal exposure to a virus through normal behavior, and living on the planet and interacting with other people. So, we should think about HPV in the head and neck in exactly the same way. In fact, if you go back and look at exposure to HPV, essentially everybody is exposed to it by their mid-20s; as we say, otherwise known as going to college. When you are exposed to other individuals on the planet, this virus, that’s persisted for decades and decades, gets passed back and forth. In fact, it’s quite a hardy virus. Often, if you look in the laboratory, it’s a contaminant sitting on the bench top. It’s passed on the skin. So, by no means, does exposure to HPV require promiscuous behavior.
Now, that’s not to say that individuals who have a high number of lifetime sexual partners and certain behaviors don’t have a higher risk of exposure or re-infection. And it’s possible that re-infection or multiple infections really do increase the risk. So, we have to balance that when we educate patients. HPV is a normal virus that we’re all exposed to on the planet, and that, it, in some individuals, causes cancer and in the vast majority of us is eliminated. It’s just cleared. At the same time, those individuals with high exposure, multiple infections, are at a higher risk of HPV-positive head and neck cancer.
The second or the third question that comes is, well, does the vaccine that’s approved—and there’s not one, there’s a few vaccines from several companies—does that vaccine portend any value for preventing head and neck cancer driven by HPV, since we know it works for cervical cancer? All of the data would suggest that that should be protective. One piece of evidence is that the HPV type, which is type 16, which is responsible for 50% to 60% of cervical cancers, is responsible for approximately 90% of the head and neck cancers. So, the type that’s being targeted with the vaccine in the cervix is actually the same type, and, in fact, more dominant in the head and neck. That would suggest that the vaccine could protect from head and neck cancer.
There’s really only one published study. More are emerging. But there was a study of a Costa Rican cohort of young women who got either the HPV vaccine or, in a randomized fashion, a hepatitis A vaccine. Those women had donated saliva 4 years after vaccination. And they found a dramatically lower prevalence of HPV DNA, HPV infection in the saliva of women who got the HPV vaccine versus those who got the hepatitis vaccine.
Since we know that multiple re-infections and persistence of HPV in the oral cavity is probably associated with increased risk, and there’s a few steps there, that would suggest that there may be a protective effect down the road for HPV-positive head and neck cancers. But, that’s decades off, because we know that the exposure by your mid-20s is still 2 decades or 3 decades before most HPV-positive head and neck cancer patients show up. So, there’s a lag between any benefit of the vaccine, which we’re all hopeful for, and what the data suggests will be beneficial and actually transmitting to lower rates of the HPV-positive cancers. Then it shouldn’t go unsaid that the lack of vaccine uptake in the US, because it’s not mandated, is a major public health stumbling block and hurdle to having this cancer vaccine prevent cervical and other anogenital and head and neck cancers. A number of locations around the country have been analyzed, and uptake in girls is around 30% or 40%. In boys, it’s 10% or 20%. So, this vaccine is FDA-approved in boys and girls. Most of us think that since obviously the girls, in general, are being exposed through interaction later in life to males, vaccinating both is the most effective way to prevent HPV from causing this type of cancer. We encourage it, and we need higher rates of uptake.
One question with regard to the HPV vaccine is we’ve already addressed that it’s approved for both boys and girls. The age is 9-24, in that timeframe. Most everybody is exposed by their mid-20s and that’s why the FDA only approved it into the mid-20s because, at that point, everybody has been naturally exposed. And when I say everybody, it seems like around 80%, because it’s a little bit harder to detect a fleeting, short-term infection if it’s not. You don’t seroconvert, for instance, with antibodies. But the problem is when you have a natural infection to HPV, you form antibodies against the coat, or the capsid protein L1. The vaccine itself intends to generate antibodies against L1, and so it’s essentially an empty shell virus. There’s no viral DNA there. It’s just an empty shell to induce seropositivity. We think that that virus, after age 24, or after the first exposure naturally, the vaccine won’t induce those antibodies because of preexisting exposure, preexisting antibodies that clear the vaccine from being able to do its job and cause a stronger seropositive response.
So, the question we get asked by patients is, can I use this prevention vaccine for therapy? And we think the answer is, no. That’s not just theoretical or speculative, it’s from looking in the cervical field. When they looked at women with cervical intraepithelial neoplasias, those who had been previously exposed and had preexisting baseline seropositivity derived no benefit from the vaccine. In the control groups and in the vaccine groups, they had the same rate of cervical pre-malignancies if they were previously exposed and had previous seropositivity. In the naive women who did not have baseline seropositivity, they did benefit from the vaccine. So, we don’t think that the prevention vaccine will be useful in patients or individuals either, previously exposed and seropositive, or those who have an active HPV-induced cancer.
Transcript Edited for Clarity