Source: www.targetedonc.com
Author: Jordyn Sava


In an interview with Targeted Oncology for Head and Neck Cancer Awareness Month, Noel Laudi, MD, MRCP, discussed the link between human papillomavirus infection and head and neck cancers.

There is a complex relationship that exists between human papillomavirus (HPV) and head and neck cancers. According to Noel Laudi, MD, MRCP, “no one is immune to HPV-related head and neck cancers, with certain demographics at higher risk.”

Common areas of occurrence for HPV-related head and neck cancer are in the mouth, including tonsils, soft palate, oropharynx, and base of tongue. HPV can cause cancer by staying in the system for 1 to 3 years and affecting lymphatic tissue in fertile areas of the mouth.

HPV-related head and neck cancers often present late due to silent growth. Those at a higher risk of developing HPV-related head and neck cancer include those with more sexual partners and those exposed to oral sex. Additionally, smoking increases the risk of cancer for those with HPV, creating a double risk with the virus and smoke.

Laudi, of Allina Health Cancer Institute, emphasized that the HPV vaccine is effective in preventing these cancers, with the ideal age for vaccination being around 11 to 13 years old. However, there is an unmet need for better screening methods and higher vaccination rates of children to prevent HPV-related cancers.

“I think the vaccine has been a huge move in the right direction. The treatment is very tough, and if we can prevent the cancer with a simple injection when we are 11 or 12 years old, I think that is going to decrease and maybe even eliminate HPV-positive head and neck cancer,” explained Laudi.

In an interview with Targeted OncologyTM for Head and Neck Cancer Awareness Month, Laudi discussed the link between HPV infection and head and neck cancers.

Targeted Oncology: Can you explain the link between HPV infection and head and neck cancers? How does HPV contribute to the development of these cancers?
Laudi: HPV, also known as human papillomavirus, is 1 of the most common viruses which can cause cancer in general. Most people are aware of HPV in association with cervical cancer in women. However, we are seeing now that HPV causes more head and neck cancers than cervical cancer. There are many different subtypes of HPV, more than 100 subtypes, but only a few can cause cancer. The prominent subtype of HPV which causes head and neck cancer is HPV16. Head and neck cancer can occur in 2 main patient populations. Traditionally, it was attributed to smoking and alcohol usage. As people are becoming more aware of the harm of smoking and less people are smoking, the incidence and the percentage of head and neck cancer caused by the virus is going up because as the percent of throat cancer from smoking is getting less with time, the percentage of the virus causing head and neck cancer is going up with time.

Now, where does HPV cause cancer in the head and neck? Number 1, head and neck is basically from your mid-forehead, so the sinuses, all the way down to the voice box. Cancer can happen anywhere in that area. HPV, once it gets into the system, particularly to the mouth, tends to settle on fertile ground, mostly where there is lymphatic tissue. Most HPV-positive cancers are going to occur in 4 main spots: the tonsils; the soft palate, which is basically just above the tonsils; the oropharynx, which is the space behind the mouth; and the base of the tongue. One can get HPV in other areas of the mouth, so in the larynx, the base of the mouth, the jaw or the anterior tongue, but predominantly those 4 places.

Secondly, how does it cause cancer? A virus is made mostly of DNA and protein. We are all exposed. Most people in the world have been exposed to HPV, some way or another. The virus can be carried on the hands, the virus can be carried through a cup, so most of us will be exposed to the virus, almost all of us, at some time in our lives. However, the immune system is able to get rid of the virus. Usually, the virus stays in the system for about 1 to 3 years. In most people, 90% of people, the virus is cured naturally. In about 10% of the patients, the virus is not cured. The virus will occur, and patients do not know it because it does not cause pain, does not cause irritation, does not cause problems with swallowing, eating, appetite, or even taste. But year after year, the virus can slowly, just like a seed in the ground, take 1 to 4 years to develop roots, and that is what happens. Slowly, the virus can penetrate into the wall of the tissue of the mouth or the oral cavity and slowly gets infected and infects the cells deep in the throat. Once it does that, it penetrates in between the layers like water penetrating into the walls of a cracked wall. Once it gets there, it can infect the cells.

Now, if a cell dies, so the HPV cell, then no harm is done because the cell is dead. The problem is it is almost like that plane did not leave the ground. Everything is destroyed by the virus. Then [we] have a problem because that cell has become a cancer cell. That process might take years, sometimes 20 to 30 years from the time you have been infected. But now you have a cell infected by a virus, that virus has created a DNA damage, and that cell becomes aggressive and can grow. Without the control, 1 cell makes 2, 2 will make 4, 4 will make 8, etc. Within a few months, once that process starts, you get cancer.

What are the risk factors for developing HPV-related head and neck cancers? Are there certain populations or demographics more susceptible?
I do want to emphasize that no one is immune. People who are more exposed to the virus are more likely to develop this cancer. If we take the population and look at the people who have developed the cancer, [we] look back and say, out of 1000 people, 20 developed HPV cancer, and then we look back at those 20 people who developed HPV cancer and start to study their behaviors. There is a pattern. The pattern is that several of these patients tend to have more than 1 sexual partner. The risk of HPV increases in proportion to how many partners someone has. If someone has 1 partner, there is still some risk, but the risk is more if you have 4 or more sexual partners.

Secondly, people who are exposed to oral sex will have a higher risk of HPV. The virus can stay both in the oral cavity but also with the genitalia. Needless to say, if [one has] had oral sex, one is more likely to be exposed to the virus. Again, a lot of us might have the virus and we just do not know. People, just by kissing, can transmit the virus. There are also data to suggest that one can transmit the virus using their cigarette or even from the hands. One can get the virus in many different ways. But in terms of who is more likely to develop the cancer, I would say people who have had more than 3 or 4 sexual partners, especially if the partners have been exposed or have HPV themselves.

How common are HPV-related head and neck cancers compared with other types of head and neck cancers?
The incidence and the percentage are going to depend on the site of the cancer itself. If we take the front portion of the tongue, larynx, or the nasopharynx, most of those will not be HPV positive. For example, in the larynx, 90% of those cancers are going to be related to smoking, or the hypopharynx, which is the area below the throat. In terms of the nasopharynx, that is caused by a different virus, the Epstein-Barr virus, which is the virus which causes mononucleosis. Laryngeal cancer and hypopharyngeal cancer, cancer below the throat or below the neck, is caused often by smoking. When it comes to oropharyngeal cancer, the base of tongue and tonsil, probably 70% of those cancers are HPV-positive or HPV-related. But 30% have got to be just smoking.

Now, one might say, well, if it is HPV-positive, doesn’t that mean that it is caused by the virus? What if somebody is positive for the virus, but also smokes? Well, if you smoke and have the virus, it is like having a bat in the cockpit and the fire in the cockpit at the same time. Now we have 2 problems. The point is that if you have the virus and you smoke, that increases the chances of cancer happening in the oropharynx, the base of the tongue.

What are the symptoms of HPV-related head and neck cancers compared with non-HPV-related head and neck cancer? What distinguishes them?
There are a couple of differences. Number 1, it depends where the cancer is coming from. The problem with HPV-positive cancer is that that often affects the oropharynx. As you might remember, the oropharynx is the tonsils, the base of tongue, the soft palate, and the wall of the oropharynx. The reason I am mentioning those is that we do not look in the mirror and look at our tonsils every day. The only time we do that is when we go to the dentist. Unfortunately, it tends to be a silent growth. By the time it grows,this is for HPV specifically, by the time it manifests, it manifests with either somebody having trouble swallowing, like feeling something getting stuck, maybe by accident going into a dentist, or more typically presented with a big lift out in the neck. That can be also with smoking. The differences of course would be that smokers, if the cancer is coming, let us say in the larynx, one can have hoarse voice, or if the cancer is coming in the entire time, you can fill it with your teeth. Or if the cancer is coming in the jaw, you can have pain. The problem with HPV-related cancers is they often present late because the growth is silent and quiet and by the time you have symptoms, it tends to be later in time.

How effective is the HPV vaccine in preventing HPV related head and neck cancers? And what is ideal age individuals should start receiving this?
I think that is probably where the money is, so I am going to split it into 2 ways. One, once [a person] gets HPV-positive cancer, can you treat it? The answer is yes. But admittedly, the treatment is not a picnic. Whether that is surgery, radiation, or chemotherapy, it is quite toxic and tough, and your life will not be the same after treatment.

The point is prevention is better than cure. The efficacy of the vaccine is almost 100%. The vaccine protects against 4 main types. Two of them are the leading causes of cancer, HPV16 and HPV18, and that is included in Gardasil, in the vaccine. Ideally, the earlier [we vaccinate] the better. It is recommended to start as young as 9. Most experts have started to give it to 11 or 12 year old kids, or at a young age because the sooner the better. It is effective, almost 100%, at preventing HPV, so if you do it before you are exposed, it is quite safe, and one may get a lot of benefit from it. It will almost eliminate the chance of getting HPV. In so doing, because HPV the virus cannot survive in the body, if [one] already has antibodies from the vaccine, it significantly reduces the risk of both cervical cancer and head and neck cancer. [One] can get the vaccine even up to 40 years of age, so between 11 and 40, but the focus and the emphasis is to get it as young as you can.

The other thing is who should get the vaccine? Girls, boys, or both? The answer is both for many reasons. If we give it to just girls, boys can also share cutlery, boys can also share stuff. One thing that we did not mention is that HPV-positive oral cancer is more common in boys than girls coming in with the ratio of about 4 to 1. For every 5 patients with oropharyngeal cancer from HPV, 4 are going to be men, and 1 is a woman. I think it is also important to focus on men for that reason. Plus, if a man has HPV, they may give it to a girl as well who may not have been vaccinated. By vaccinating both, we are going to achieve herd immunity.

What barriers exist in promoting the HPV vaccine for cancer prevention, especially in the context of head and neck cancers?
It is a misconception of vaccines. A vaccine is a sample of the virus. The body organizes the protein on the vaccine and produces antibodies so that when exposed to the virus, your B cells, your immune system, is ready to attack because it is already on alert. I think it is a misconception that people do not want to get poisons in their body. The second thing is, maybe because we can also screen for cervical cancer, people focus more on cervical cancer, but forget that HPV-positive at the neck cancer is becoming more common than cervical cancer. The other problem to remember is that, even if [one has] HPV in the cervix, [we] can screen for that. We can do something early to prevent it from turning into cancer. However, there is no good screening for head and neck cancer. And so, the problem is, we cannot find it early because there are no screening tests. That is why I think it is even more important to think about head and neck cancer and focus on [educating] the general public because it is becoming an epidemic.

Can you discuss any ongoing research or clinical trials that are happening in this space?
I think the vaccine has been a huge move in the right direction. The treatment is very tough, and if we can prevent the cancer with a simple injection when we are 11 or 12 years old, I think that is going to decrease and maybe even eliminate HPV-positive head and neck cancer. One thing also to remember is if you vaccinate every kid between 11 and 13 in America, let’s say today, we will start seeing a drop in about 20 to 30 years from today because most of these cancers develop between age 30 and 60 or 70. We have to wait until at least 20 years from that 11-year-old to become 30, so there is going to be a lag before we start seeing a nice decline. That is assuming that most, 90% or more, of the kids are being vaccinated today.

Two, immunotherapy. The immune system is important in attacking, killing, destroying, and defending the body against cancer, particularly oropharyngeal HPV-positive cancer. Immunotherapy can and does have a role in activating the immune system and trying to make the immune system take over the cancer. That has been used a lot in head and neck cancer, especially when it is spread, but also when it is localized. The third thing is HPV-positive oropharyngeal cancer tends to be more sensitive to the effects of radiation [or] chemotherapy, than smoking-related head and neck cancer, basically [because of] the way the cancer is formed. [People are looking to see], could we do less radiation with less morbidity, less damage by doing less treatment for HPV-positive tumors? Do all these patients need chemotherapy as opposed to tobacco-related cancer? Maybe we do not need as much chemotherapy, maybe we need less. That is where the future is trying to go. Deescalate and try to treat the cancer without compromising the treatment, but with the lesser [adverse] effects because we are decreasing the intensity of the treatment.

Do you have any advice for oncologists this head and neck cancer awareness month?
Vaccinate children to protect and prevent this cancer from happening. Number 2, there is no good screening for this cancer, and number 3, it is more common in people who have more than 1 or 2 sexual partners. It is treatable, and most of these cancers, probably 80% to 90%, are curable if it has not spread outside the throat or head and neck. We are looking into research to try to deescalate the treatment for this cancer because it does respond better than the tobacco associated with head and neck cancer.