What is HPV-positive head and neck cancer?

HPV stands for human papillomavirus, a common virus that can cause certain cancers. When we talk about HPV-positive head and neck cancer, we're referring to cancers that developed because of this viral infection.

In the head and neck region, HPV most commonly affects the oropharynx, which includes the tonsils, base of the tongue, and nearby tissues in the throat. This is different from other head and neck cancers that might be caused by tobacco use or alcohol consumption.

What makes HPV-positive cancers special is that they behave very differently from cancers not caused by HPV. The good news is that HPV-positive cancers usually respond much better to treatment than their HPV-negative counterparts. People diagnosed with HPV-positive head and neck cancer also tend to live longer and have better outcomes overall compared to those with HPV-negative disease. This difference in behavior is so significant that doctors now consider HPV-positive and HPV-negative head and neck cancers to be essentially two different diseases that require different approaches to treatment.
 

When cancer comes back or spreads

Even though HPV-positive head and neck cancer often responds well to initial treatment, it can sometimes return (recurrent disease) or spread to other parts of the body (metastatic disease).
Most people diagnosed with this type of cancer first receive curative treatment, which might include surgery, radiation therapy, chemotherapy, or a combination of these approaches. The goal of this initial treatment is to completely eliminate the cancer from the body.

However, despite the generally favorable outlook for HPV-positive cancers, some patients will experience cancer recurrence months or years after their initial treatment. When this happens, the cancer might come back in the same area where it originally started, appear in nearby lymph nodes, or spread to distant organs like the lungs, liver, or bones.

If the cancer does return locally or spread after initial treatment, your care team will need to adjust your treatment plan significantly. At this point, the focus shifts to one of two main approaches: either attempting another curative treatment if the recurrence is caught early and in a limited area, or transitioning to treatments aimed at controlling symptoms, slowing the disease's progression, and maintaining your quality of life for as long as possible.
 

First step: Can it still be cured?

When cancer returns, your care team will first check whether there's still a chance for cure. This is one of the most important evaluations your doctors will perform, as it determines the entire approach to your future treatment.

Surgery may be an option if the cancer has returned to a location that can be operated on safely. Your surgical team will carefully evaluate whether the recurrent tumor can be completely removed without causing unacceptable damage to vital structures or functions like speech and swallowing.
Another possibility is re-irradiation, which means giving radiation therapy again to the area where cancer has returned. Modern radiation techniques allow doctors to deliver precise doses of radiation while carefully limiting damage to healthy tissues that may have been treated before. This approach requires sophisticated planning to balance effectiveness against the risk of complications.

For some patients, targeted local treatments might be appropriate, particularly if the cancer has spread to only a small number of spots. These treatments could include highly focused radiation techniques like stereotactic radiation or surgical removal of individual metastatic sites. This approach, sometimes called treating "oligometastatic" disease, aims to eliminate all visible cancer with localized treatments.

If careful evaluation shows that these curative options aren't possible due to the location, extent, or number of cancer sites, then treatment shifts its focus. In these situations, the goal becomes controlling the cancer's growth, improving symptoms you may be experiencing, and maintaining your quality of life for as long as possible.

Current standard treatments when a cure isn't possible

Immunotherapy has revolutionized how recurrent and metastatic head and neck cancer is treated, offering new hope for patients whose cancer cannot be cured with surgery or radiation alone.

Immunotherapy works by helping your own immune system recognize and attack cancer cells more effectively. Think of it as removing the brakes that cancer uses to hide from your immune system, allowing your body's natural defenses to fight the disease. The most commonly used immunotherapy drug is pembrolizumab, which can be given either alone or in combination with chemotherapy, depending on specific characteristics of your tumor found through laboratory testing.

Whether you receive immunotherapy alone or combined with chemotherapy often depends on the results of a test called PD-L1. PD-L1 is a "marker" or protein found on cancer cells that helps doctors predict how well immunotherapy might work for your particular cancer. If your tumor shows high levels of PD-L1, immunotherapy alone may be sufficient to control your disease effectively. However, if your tumor has lower PD-L1 levels, your oncologist will likely recommend combining immunotherapy with chemotherapy to maximize the treatment's effectiveness.

Other treatment approaches are also available for patients who may not be candidates for immunotherapy or whose disease has progressed despite immunotherapy treatment. Chemotherapy plus cetuximab represents an older standard of care that is still used for some patients who cannot receive immunotherapy due to autoimmune conditions or other medical reasons.

Clinical trials offer access to cutting-edge treatments that may not yet be widely available. These research studies are testing promising new approaches, including therapeutic vaccines specifically designed to train the immune system to target HPV proteins found in your cancer cells. Researchers are also investigating new targeted drugs, including innovative "bispecific" antibodies that can attack cancer cells in multiple ways simultaneously, as well as novel combinations of immunotherapy with other therapies designed to improve treatment results and overcome resistance mechanisms.
 

Looking to the future

Rates of HPV-related head and neck cancers are rising and may peak in the 2030s. This ongoing increase represents both a significant public health challenge and an area of intense medical focus.

The good news is that prevention through HPV vaccination offers tremendous hope for reducing future cases. As more people receive HPV vaccines, particularly during adolescence before exposure to the virus, we expect to see significant reductions in HPV-related cancers over the coming decades. This means that many future cases of this disease could be prevented entirely, similar to how vaccination programs have reduced other preventable cancers.

At the same time, the current rise in cases has intensified research efforts to develop treatments that are more effective, less toxic, and longer lasting than current options. Scientists and doctors are working to better understand what makes HPV-positive cancers unique so they can design therapies specifically tailored to this disease. This includes developing treatments that target the virus itself, creating more sophisticated immunotherapy approaches, and finding ways to maintain the excellent cure rates we see with initial treatment while reducing the harsh side effects that can impact quality of life.

The research community is also focused on helping the growing number of patients who do experience recurrent or metastatic disease live longer, better lives. This includes not only developing new drugs and treatment combinations but also improving supportive care, managing treatment side effects more effectively, and addressing the unique needs of patients with HPV-positive cancer, who tend to be younger and may face decades of survivorship after treatment.
 

Questions to ask your doctor

●    Is my cancer HPV-positive?

●    Could my cancer still be cured?

●    What are my treatment options now?

●    Am I eligible for a clinical trial?

●    What are the side effects of each treatment, and how can they be managed?

●    How will treatment affect my daily life?
 

Key takeaway

HPV-positive head and neck cancer is different from HPV-negative disease — and that’s often a good thing, because it generally responds better to treatment. Even if the cancer comes back or spreads, there are more treatment options today than ever before, including immunotherapy, targeted therapies, and clinical trials.

Knowing your options and asking the right questions can help you and your care team make the best plan for you.

The content of this article has been algorithmically generated by an AI model trained on a wide range of data and is based on a Grace's video transcript from our 2025 HPV Advances Program - https://www.youtube.com/playlist?list=PLWsyUmdjLXhG-0WQu_fdwbhehHJfLKumS  Verified by Joseph Steward, Medical Writer.

Every effort has been made to ensure the quality and reliability of the content; however, limitations, inaccuracies, or biases may exist. The content should not be considered a substitute for professional advice, and we recommend seeking professional guidance and independently verifying the information before making decisions based on this content.