Less Intense Treatment Strategy Cures Many HPV-related Cancers

Almost 80 million people have been infected with human papillomavirus (HPV), which is now the most common sexually transmitted infection in the United States. Most people are able to clear the HPV virus without being treated, but those who can’t are at increased risk for developing cancer in the tonsils and base of the tongue.

Aggressive treatments developed for tobacco-related head and neck cancers over-treat most patients with HPV-related cancer. A new, less intense strategy is curing many of these patients while preserving their ability to swallow, speak and eat. Our approach resulted in the nation's leading survival rate for HPV-related cancers: ~95% of our patients were still alive after two years, and patients treated with reduced radiation were less likely to need feeding tubes. 

Medical oncologist Alexander Pearson, MD, PhD, co-director of the head and neck cancer program at the University of Chicago Medicine, discusses HPV-linked head and neck cancer and new treatments for the disease.

The HPV virus produces a number of proteins that help it hide from the human immune system, which normally would be able to detect and kill these cells. One of these HPV proteins, E6, shuts down an important tumor-suppressing genetic regulator of cells. Another HPV-produced protein increases the division rate and metabolic activity of infected cells. Over time, more genetic changes accumulate in these infected cells, which eventually become precancerous, then actual cancer. HPV type 16 accounts for more than 90% of HPV-related cancers.
HPV-related cancers, including cervical, penile, anus and vulvar cancers, are increasing because the number of HPV infections has gone up in the general population. For instance, HPV-related oropharyngeal cancer — that’s cancer in the middle part of the throat, which includes your tonsils and the base of the tongue — is thought to be due to changing sexual practices over the last four decades, including an increase in oral sex. 
Treating HPV-related head and neck cancers depends on the stage, or how advanced, the cancer is in the body. Some cancers can be treated with surgery or radiation alone, while others require treatment combining surgery, chemotherapy and radiation. Because head and neck cancers have a high chance of returning, treatments were designed to be very intense. This was when most tumors weren’t related to HPV. The side effects of these treatments relate to their amount and intensity. This can lead to needing a feeding tube or difficulty swallowing. 

We started with clinical research — the OPTIMA study was designed to determine if we could successfully decrease the intensity of treatment based on how well a patient’s cancer responded to chemotherapy. In other words, if a tumor shrinks more with chemotherapy, it’s less likely to resist radiation — meaning we could cure patients using 40% less radiation focused on a smaller area. It’s called “de-escalation,” and the results were very exciting. We had excellent survival rates: 95 percent of the patients were still alive after two years. And patients treated with less radiation were less likely to need feeding tubes. 

Comparison of de-escalation trials showing UChicago OPTIMA trial outperformed similar approaches at other medical centers
This table compares progression-free survival (PFS) rates for published de-escalation treatment clinical trials conducted in the United States. UChicago Medicine's nation-leading survival rate is a direct result of our advanced approaches to optimize patient outcomes and survival while minimizing toxicity. This table was originally published in the American Society of Clinical Oncology (ASCO) 2020 Educational Book.

Learn more: PubMed study abstract or read the original study published in the Annals of Oncology (PDF)

Researchers still aren’t sure; some HPV-related cancers can be very aggressive. One answer may lie in our immune system’s natural ability to identify viruses, and our potential to “re-awaken” the immune system in the fight against cancer. We’re excited to be using new immunotherapy drugs to treat both HPV-related and HPV-negative head and neck cancers.
Cure rates for all HPV-related head and neck cancers across the country are greater than 80%, with UChicago Medicine's nation-leading survival rate of ~95%. But it depends on the stage of the cancer. Unfortunately, we haven’t yet figured out a way to successfully cure all HPV-related cancers.
We’re in the process of studying which patients benefit the most from this strategy through clinical trials, including a follow up to the OPTIMA study. A de-escalation strategy should be used carefully and as part of a clinical study at this time. We do, however, have decades of experience using other therapies. Whether or not a patient chooses to be treated through a clinical trial, we use our experience to choose the right kind of treatment for each patient, given the tumor characteristics and medical needs.
There are risks with any treatment, including within a clinical trial. That’s why it’s important to get your treatment at a hospital with lots of experience in this area and to talk to your doctor to weigh the pros and cons of de-escalation treatment and if it’s right for you.
We recently completed OPTIMA II, a follow up to the OPTIMA study. In OPTIMA II, we also included immunotherapy with chemotherapy to evaluate how HPV-related tumors respond. Some patients may skip radiation treatment altogether and have robotic surgery if they’ve got tumors that are appropriate for removal. We again found excellent survival rates with lower side effects in patients who qualified for less intensive treatment. New techniques in robot-assisted surgery for this cancer result in fewer side effects, which means patients heal faster, and were able to forego radiation therapy altogether. Learn more: Journal of Clinical Oncology abstract

We are building on these results by evaluating novel ways to select patients for de-intensified treatment, such as blood and saliva tests.
Gardasil 9 is an FDA-approved HPV-prevention vaccine for people between the ages of 9 and 45. One of the HPV strains it protects against is HPV type 16, which causes the majority of HPV-related cancers. Unfortunately, many unsubstantiated myths have been spread about this vaccine and others. 
Head & Neck Cancer: Q & A

Medical oncologist Alexander T. Pearson, MD, PhD, and nurse navigator Patricia Heinlen, BSN, RN, discuss head and neck cancer, including the HPV vaccine and how new treatment approaches are tailored to each patient's cancer type, making treatments more effective while reducing side effects.

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