Risk Factors, HPV, and the Latest in Head and Neck Cancer: Q+A with Drs. Fatemeh Momen-Heravi and Angela Yoon

To prevent cancer, a trip to the dental chair is equally as important as keeping up with other routine physical exams and screenings. That’s what oral cancer specialists Fatemeh (Flora) Momen-Heravi, DDS, PhD, MPH, MS, and Angela Yoon, DDS, MPH, MAMSc want you to know. As researchers, they are investigating new treatments, such as immunotherapy, for patients with head and neck cancer, and studying new ways to personalize treatment. Immunotherapy is a promising new treatment  that harnesses a person’s own immune system to fight cancer. 

 
Head and neck cancers include cancers that mostly begin in the surface linings of the mouth, lips, nose, and throat. Head and neck cancers, with oral cancer being the most common type, account for about 4% of all cancers in the United States. Smoking and heavy alcohol use is known to increase the risk of head and neck cancer, and more recently, cancer-causing subtypes of human papillomavirus, or HPV, also is a high risk factor.

Dr. Momen-Heravi is exploring the molecular mechanisms of head and neck cancer progression and communication of cancer cells within tumor microenvironments and their link to other diseases, including diabetes and periodontal (gum) disease. She also is researching how head and neck cancers affect different populations based on race or ethnicity. Dr. Yoon is interested in identifying prognostic biomarkers for oral cancer and teasing out which patient population is at an increased risk of mortality.
 
Drs. Momen-Heravi and Yoon, faculty at the Columbia University College of Dental Medicine, discuss the latest in head and neck cancer prevention, research, and treatment.

How are head and neck cancers diagnosed and can they be prevented?  
Angela Yoon (AY): The mouth cancers appear as non-painful white or red patches typically on the tongue and floor of the mouth. The ones involving the nose and throat may cause patients to have trouble breathing or speaking, or experience pain when swallowing or cause hoarseness in their voice.  Once diagnosed, X-rays and other imaging procedures are performed to examine if cancer has spread to other parts of the body. 

The best way to prevent cancer is to detect it early at the pre-cancerous stage and treat it with a simple surgical procedure before it becomes cancer. Head and neck pre-cancer can be detected during routine visit to your doctor and dentist so it is important to not skip these annual or bi-annual exams. 

A sub-set of head and neck cancers have been linked to HPV. What do we know now about HPV and head and neck cancer?
AY: The human papilloma virus (HPV) subtype 16 and 18 are the cancer-causing strains of HPV and are considered the high-risk forms of the virus that can lead to certain cancers. So far, we know that these HPV strains can lead to cervical, anal, and throat cancer. These HPV strains encode proteins that induce tumor formation, and we typically see HPV-induced cancer appear in the throat, not in the mouth. Less than 4% of oral cancer cases are due to HPV, and typically in patients who are already immunosuppressed. But around 70-80% of throat cancers are due to these HPV strains, and we still are not clear exactly what’s driving that.

What are the other major risk factors of head and neck cancer? 
Fatemeh Momen-Heravi (FMM): I think it’s known that tobacco use and alcohol use are  risk factors for developing  some cancers. But I think what people may not know is that combining both uses really does puts you at a much greater risk of developing head and neck cancer; a patient who is both a heavy smoker and drinker is 30 times more likely to have head and neck cancer. 

Unfortunately, in our own neighborhood (Washington Heights and Upper Manhattan), alcohol and tobacco use is prevalent. I am collaborating with the Community Outreach and Engagement office at the Herbert Irving Comprehensive Cancer Center on awareness and prevention programs specifically for our community to increase awareness of not just the dangers of alcohol use and tobacco use, but also the problems they can lead to if done together. 

AY: Head and neck cancer used to be thought of as a cancer that occurs mostly in older men. Now we’re seeing an increase of younger women developing oral cancer, and we’re not sure what’s driving that trend yet. Also, people who aren’t at risk for head and neck cancer but then develop oral cancer tend to have a more aggressive form. So no one is really free from developing head and neck cancer, which is why regular checkups are strongly recommended, especially since oral cancer is painless and can go unnoticed. 

How is head and neck cancer treated? What are some of the latest advancements in care?  
AY: Currently, the treatment of head and neck cancer depends on the extent of disease (clinical stage). The main treatment is still surgery first, followed by radiation therapy and/or chemotherapy. In some patients, targeted therapy, or a combination of treatments are being offered through clinical trials, like neoadjuvant therapy which is when we treat the patient with chemotherapy or immunotherapy before they have surgery. Right now it is an exciting time to research new therapies for head and neck cancer. We are in experimental stages of novel therapeutics, with a lot of new treatments in the pipeline. 

FMM: In 2016, the FDA approved the first immunotherapeutic agents – the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab – for the treatment of patients with recurrent head and neck cancer who failed to respond to conventional chemotherapy. While some patients respond to these new drugs, we are still only seeing a fraction of patients benefitting from the treatment. But because head and neck cancer is a complex disease comprising a multi-mutation landscape, we have a lot of work to do still in order to really deliver targeted therapy for each patient. So there are promising cancer immunotherapies for head and neck cancers but there is more research that we are doing in order to get that more emerging, personalized therapies to work for our patients. 

What are you currently working on and most excited about? 
AY: My research has been focused on examining the cancer tissue in patients at the time of diagnosis to identify people who may have poor prognosis, despite being in the early clinical stage. These are known as prognostic biomarkers. In this work, we’ve identified a set of molecules, called microRNAs, that makes the cancer more aggressive than others. Combining the amount of microRNAs present in the tumor tissue with the clinical stage and microscopic diagnosis, we’ve developed an algorithm to calculate individual risk score. A risk score of two or higher will inform doctors that additional treatment is required to improve chance of survival, even if the individual is in early clinical stage (stages I and II). 

We also have plans to deliver cancer vaccine for those ‘high-risk’ individuals, which can be given after the surgery to prevent cancer from recurring. These are exciting advances in head and neck cancer allowing us to custom tailor survival assessment and treatment for each person affected with this cancer.

FMM: My lab is working to understand the mechanisms of cancer progression and how cellular cross talk with immune cells play a role in head and neck cancer.  We are also working on developing targeted therapies by utilizing the body’s natural transport system—exosomes—as a delivery platform for targeted gene editing and drug delivery for treatment of head and neck cancer. Exosomes are small vesicles shed by all cells in the cellular microenvironment which carry and deliver biomacromolecules. 

I’m working with collaborators at Columbia to identify the genomic and molecular profile of head and neck cancer in Black and Hispanic patient cohorts in our catchment area, and we have already identified molecular changes and mutations in patients with African and Hispanic ancestry that have not yet been reported. Specifically, the Black patient cohort shows higher incidence rates of head and neck cancer than the white population. Black patients initially present with more advanced cancers than white patients, and Black patients also show a worst 5-year survival rate in all types of head and neck cancer. Lastly, mortality rates are also worse in Black patients versus white patients. We’re aiming to complete a comprehensive picture of all of the biological differences between these racial groups. With this more complete picture, we can develop more effective therapies and help to advance personalized medicine in head and neck cancer.