Sex joins tobacco and alcohol as a cause of head and neck cancer

HPV word cloud

A generation ago, tobacco use — smoking and chewing —and alcohol consumption were the leading causes of head and neck cancer. In the last 10 to 15 years, as rates of smoking decreased, the frequency of smoking-related cancers has fallen. At the same time, however, infection with cancer-causing human papillomavirus (HPV), especially HPV type 16, has become an increasingly frequent cause of head and neck cancer, especially oropharyngeal cancers, which affect the tonsils and the base of the tongue.

The good news: it’s potentially preventable – IF you are vaccinated against HPV as a teenager. Fortunately, the vaccine can be highly effective at preventing HPV-related cancers. Unfortunately, the vaccine does not protect people who were exposed to HPV during sexual contact before getting vaccinated.

The bad news: more and more people are affected.

Because the vaccine did not become available until 2006, most adults remain at risk. As many as 80 percent may have already been exposed.

The incidence of oropharyngeal cancers caused by an HPV infection has increased dramatically, according to the Centers for Disease Control and Prevention. In the 1980s, fewer than 20 percent of oropharyngeal cancers were attributed to HPV. Now, more than 70 percent of these cancers involve HPV and incidence rates continue to rise. Some people call this the “HPV epidemic.” Given the availability of an effective vaccine, this is a concerning trend.

Fortunately, patients with HPV-related head and neck cancers, even those with advanced regional lymph node involvement, have a better prognosis than those with alcohol and tobacco-related cancers. Long-term survival and even cure rates are typically in the 80 percent range, much better than the 50 to 60 percent seen in smoking-related (HPV-negative) head and neck cancers.

The aggressive treatments developed for tobacco-related/HPV-negative tumors, combining surgery, radiation and chemotherapy, over-treat most patients with HPV-related disease.

The aggressive treatments developed for tobacco-related/HPV-negative tumors, combining surgery, radiation and chemotherapy, over-treat most patients with HPV-related disease. Most head and neck cancer specialists agree that treatments are often disproportionately toxic in relation to the current high cure rates.

The HPV epidemic

Human papillomavirus has become the most common sexually transmitted infection in the United States. Nearly 80 million Americans, most in their late teens and early 20s, who should have received the vaccine but did not, have been infected. Many people are able to clear the virus on their own, but those with persistent infection are at higher risk of developing head and neck cancer.

HPV type 16 accounts for more than 90 percent of these virus-related cancers. HPV appears to lodge in the tonsil and back of the tongue, and if not cleared, can lead to cancer years or even decades later. Early symptoms include persistent sore throat, neck swelling and swallowing difficulties. Some people, however, have no symptoms for many years before a cancer manifests.

According to former UChicago Medicine cancer specialist Tanguy Seiwert, MD, improved therapies can disrupt cancer growth, cure many patients and preserve normal swallowing, speech and ability to eat. Working with a team of specialists, he conducts clinical trials and studies new methods to improve treatment, while minimizing side effects.

In March 2018, we asked Seiwert, who previously led the head and neck cancer program at the University of Chicago Medicine, about recent advances in the treatment of HPV-related oropharyngeal cancers.

How common are HPV related cancers?

Seiwert: These cancers used to be rare. Since 2000, however, growth and spread of HPV-associated head and neck cancers has been dramatic. The incidence rates are rising rapidly in the United States, Western Europe and more recently, Asia. We expect that to continue for at least another 20 to 30 years.

These HPV-associated cancers have a different phenotype. They affect younger, healthier patients in their prime, and can cause life-threatening disease.

What triggered this rapid growth?

Seiwert: It’s driven almost exclusively by one strain of the virus, HPV 16. While there are a few other “bad players,” HPV 16 accounts for more than 90 percent of HPV-related head and neck cancers. Infection happens through sexual contact. But it is hard, if not impossible, to detect, although efforts for screening are being developed at large centers.

Furthermore there’s a latency period that may last for decades. Many people are able to get rid of the virus over time, but some people cannot. HPV stays with them; it becomes latent. Then, decades later, a cancer emerges. Smoking appears to increase the chance of cancer arising, and certainly worsens the overall prognosis.

What makes HPV-related cancers different?

Seiwert: I think of it and treat it as an entirely different disease. Oncologists are still adapting to that shift. Most institutions provide the old standard treatment developed for tobacco-associated head and neck cancers, consisting of aggressive surgery plus radiation, or intensive chemotherapy and radiation. Side effects can be dramatic, and most patients are affected by long-term problems with speech, swallowing, tooth decay, dry mouth and diminished sense of taste and smell.

The OPTIMA approach, which has been presented at plenary sessions at large international meetings, resulted in markedly improved outcomes and reduced toxicity.

Our group, a multidisciplinary team of very experienced physicians in medical oncology, surgery, and radiation, has started to do what we call treatment “de-escalation” for patients with HPV-related cancers. This approach was confirmed by the OPTIMA clinical trial, and since then has been applied more broadly.

The OPTIMA approach, which has been presented at plenary sessions at large international meetings, resulted in markedly improved outcomes and reduced toxicity.

In a nutshell, we can now identify the 80 percent of HPV tumors that have a favorable behavior. These shrink quickly in response to a limited amount of chemotherapy. Then, we treat them with 35 to 40 percent less radiation, focused on smaller radiation fields. This approach yields dramatically fewer acute and long-term side effects. Patients recover quickly, often within two to six weeks.

The results, in my opinion, are truly dramatic. We rarely see severe radiation side effects anymore (down from 65 percent of patients to 15 percent). Virtually nobody requires a feeding tube – something that we try to avoid.

Our approach works extremely well, with a 95 percent cure rate, which is 10 to 15 percent better than reports from national series. In short – we get fewer side effects and better outcomes with this carefully limited treatment. De-escalation, tailoring treatment to each individual’s tumor, is a big change.

Are you the only program taking this approach?

Seiwert: We are not the only center attempting this. A handful of leading centers have had similar success, which is very reassuring. We think our approach to de-escalation, however, is unique, with careful patient selection, including risk stratification, and lower doses for appropriate patients. De-escalation is the emerging standard of care, an opinion widely shared within the field.

As a word of caution, however, de-escalation should only be done at large centers with extensive experience and appropriate safeguards. If you de-escalate too much, without the right checks and balances, you face the risk of the cancer coming back.

So far, we’ve been very successful and are really excited to offer patients better quality of life with excellent cure rates. Others have taken notice of these data. Our work has been highlighted at several of the leading conferences in the field.

Why would a viral-triggered disease be so different?

Seiwert: That’s an excellent, but difficult, question to answer. I can only speculate. One idea is that since these are virally associated tumors, the immune system is able to recognize foreign viral material and can help eliminate the disease. It also helps that these patients are younger, usually in better health, and may not have smoked at all, or only a little.

What’s the next step toward better care?

Seiwert: We are excited to build on these dramatically improved results with a follow-up, second-generation clinical trial. In OPTIMA 2, we add immunotherapy, bringing the patient’s own immune system into the battle.

Our hope is that these newer drugs – known as PD-1 inhibitors – will help the immune system recognize the cancer and go after it. Patients with really good responses can get the same benefits with 35 to 40 percent less radiation.

In OPTIMA 2, some patients may avoid radiation entirely. This is a dramatic change. A limited approach to surgery, known as trans-oral robotic surgery, or TORS, has a quick recovery time with reduced side effects. This can be applied to patients with excellent responses to the initial treatment and lower risk tumors. This could improve quality of life long term, and lead to a quick completion of treatment and a quick recovery.

Our radiation oncologist, Daniel Haraf, MD, professor of radiation and cellular oncology at the University, is one of the most experienced head and neck cancer radiation oncologists in the world. He has been crucial to our success in safely implementing de-escalation in the OPTIMA studies.

What other factors makes the HPV program at the University of Chicago unique?

We are one of only a handful of centers worldwide that perform high accuracy HPV testing, based on the specific subtype of HPV.

Seiwert: We are one of only a handful of centers worldwide that perform high accuracy HPV testing, based on the specific subtype of HPV. HPV16 dominates virally caused head and neck cancers. Other strains may carry a worse prognosis. We rely on high-level risk stratification in OPTIMA 2.

Is there anything new in surgery for head and neck cancers?

Seiwert: The most recent big recent advance, as I mentioned, is transoral robotic surgery. Removing tumors in the throat, on the base of the tongue or the tonsils can be difficult. This used to be done through radical surgery, requiring longer hospital stays and extensive rehabilitation.

Our team, however, includes highly skilled head and neck surgeons, with state-of-the art technology. This enables them to reach these tumors through the mouth and remove them safely, leaving only healthy tissue behind.