The link between HPV and head and neck cancers

April 06, 2021

Throat cancer now surpasses cervical cancer as the most common HPV-related cancer.

Doctors have long known that the human papilloma virus (HPV) is linked to cervical cancer. However, many members of the general public and even members of the medical community aren't aware of the strong link between HPV and head and neck cancers.

Dr. Ammar Sukari, leader of the Head and Neck Multidisciplinary Team at the Barbara Ann Karmanos Cancer Institute and associate professor in the Department of Oncology at Wayne State University School of Medicine, notes that almost 15,500 men and approximately 3,500 women were diagnosed with HPV-related oropharyngeal squamous cell carcinoma (generally considered throat cancer) in 2015. He cites statistics from the Centers for Disease Control and Prevention (CDC).

This means that oropharyngeal cancer has surpassed cervical cancer as the most prevalent HPV infection-related cancer.

Oropharyngeal squamous cell carcinoma accounts for about 30 to 40 percent of all head and neck cancers. Oncologists are seeing cases of this cancer due to HPV infection in mostly non-smokers, non-drinkers and younger Caucasian males in higher socioeconomic brackets, according to Dr. Sukari.

What is HPV?

HPV is a human-only virus that can infect skin and mucosal membranes (such as those in the mouth or anus). More than 200 subtypes of HPV can infect a human's squamous cells at the basal layer (the deepest layer) through damaged areas in the skin or mucosa.

The majority of HPV subtypes exclusively infect human skin, and specific HPV subtypes infect only the mucosa. These mucosal HPV viruses are sexually transmitted and affect tens of millions of Americans every year. HPV infections are so prevalent that the CDC states that nearly every sexually active man and woman will be diagnosed with HPV sometime in their lives.

Many times, HPV infections are asymptomatic. Nine out of 10 cases of mucosal HPV are eliminated by the human immune system. However, in 10 percent of HPV infections – specifically 20 to 40 subtype infections -- some of the infected cells survive and serve as the spark leading to different types of cancers.

This is dependent on the primary location of the infection. For example, an HPV infection at the base of the tongue could lead to tongue cancer 20 to 30 years after the initial infection.

"Some people will have changes in their DNA where the virus DNA will be embedded in those infected cells' DNA," Dr. Sukari said.

HPV cancers

HPV-related cancers include oropharyngeal cancer, cervical cancer and anal cancer. Additionally, some cancers of the vulva, vagina and penis are caused by HPV infections.

Symptoms of HPV-related throat cancer (oropharyngeal) may include swollen lymph nodes in the neck, a lump or ulcer in the throat, difficulty swallowing and/or pain with swallowing.

If caught early, HPV-related oropharyngeal cancer (HPV+ OPC) is highly curable. Treatment varies depending on cancer stage, presentation, patient's comorbidities (health conditions that the patient already has), and the medical team's expertise level in managing head and neck cancers.

As a general rule, treating most OPC requires more than one type of treatment modality and may include surgery, radiation and chemotherapy.

In the cases of locally-advanced cancer, oncologists might use a combination of chemotherapy, radiation and surgery, although chemotherapy and radiation are often adequate to cure up to 95 percent of this type of cancer, even when it has spread to less than three lymph nodes, according to Dr. Sukari.

The CDC notes that throat cancers linked to HPV have increased significantly over the last 15 years in the United States. Dr. Sukari accredits this increase to changes in sexual practices and greater awareness among doctors regarding the link between HPV and oropharyngeal cancer.

"The World Health Organization added HPV as a risk factor for oropharyngeal cancer approximately 15 years ago," Dr. Sukari said. "Before that, doctors weren't checking their head and neck cancer patients for HPV biomarkers." Biomarkers are substances or processes that are indicative of the presence of cancer in the body.

Although many doctors are more aware of the link, Dr. Sukari says there's much more work needed to raise awareness. He said the field is changing so quickly, there's a likelihood that individuals teaching today's medical students aren't yet fully aware of the scope of what he calls the HPV infection and head and neck cancer health crisis.

"Everyone knows about cervical cancer and Pap tests," he said. "The incidence of cervical cancer has been on the decline for a long time. The same needs to be done to raise awareness about HPV and its link to oropharyngeal cancer. It's very common, and it's on the rise. The red light is flashing on this disease."

Vaccine

Dr. Sukari also strongly advocates for the HPV vaccine, also known as Gardasil®, which was first approved by the U.S. Food and Drug Administration (FDA) in 2006 to prevent cervical cancer linked to HPV. In 2018, the FDA approved a supplemental application for Gardasil 9, expanding the vaccine's approved use to include women and men aged 27 through 45 years. Gardasil 9 prevents certain cancers and diseases caused by the nine HPV types covered by the vaccine.

Because of the lack of awareness of the link between HPV and oropharyngeal cancer among the public, Dr. Sukari emphasized that more people need to be aware of the benefits of receiving the HPV vaccine in preventing the incidence of many cancers in the future.

"There is some stigma around the vaccine," he said. "All those sexually transmitted diseases have a stigma around them too. Some doctors may not be comfortable discussing this with their patients or parents, in the case of pediatric practices. There is an urgent need to have a lot of work done on the part of schools, universities and public health professionals in educating the public about the HPV vaccine. The vaccine can prevent cancer nearly 100 percent of the time, both cervical cancer and oropharyngeal cancer."

Karmanos currently offers five different clinical trials for those diagnosed with HPV-related oropharyngeal cancer to test treatments created explicitly for HPV-related throat cancers. These trials have two goals in mind, the first being to increase the cure rate of these cancers and the second to minimize long-term organ damage that may occur due to different treatment modalities needed to cure these cancers.

"There are a lot of new studies and clinical trials, so we have the ability to tailor treatments," Dr. Sukari said. "We have trials that require high-level skills and specialized centers to be able to run them. We want to apply the most effective treatments while at the same time the least toxic treatments. We have most of the national clinical trials in HPV-related head and neck cancers."