Immune response to HPV impacts head and neck cancer prognosis

December 8, 2016

A new study in JAMA Oncology finds that antibodies to human papillomavirus detectable in blood serum are reliable indicators of five-year head and neck cancer survival

MINNEAPOLIS/ST. PAUL (DECEMBER 8, 2016) – Head and neck cancer patients with evidence of human papillomavirus (HPV) infection generally have a better prognosis than people without evidence of infection. A new study, “Immune response to HPV16 E6 and E7 proteins and patient outcomes in head and neck cancer” published todayin JAMA Oncology demonstrates that measuring a patient’s immune response to HPV provides a robust prognostic signal, suggesting that in the future a blood serum test for two specific HPV antibodies may replace traditional pathology testing.

“This study was a measure of immune-response to HPV and how it predicts patient outcome. Importantly, we investigated this question for all patient groups, and not just patients with oropharyngeal cancer which allowed us to determine that HPV was important for all forms of head and neck cancer,” said lead author Heather Nelson, Ph.D., M.P.H., co-leader, Screening, Prevention, Etiology and Cancer Survivorship (SPECS) Program, Masonic Cancer Center, University of Minnesota, and associate professor, School of Public Health, UMN.

The authors demonstrate that this immune response to HPV was beneficial for head and neck cancer patients irrespective of the anatomic location of tumor, or personal history of tobacco and alcohol consumption.

Assessing antibodies

The study examined blood serum samples and five-year survival rates among more than 1,000 Boston-area head and neck cancer patients diagnosed between 1999 and 2011. Overall, those who tested positive for antibodies to the oncogenic HPV proteins E6 or E7 were significantly less likely to die during the five-year follow-up period after diagnosis compared to those who tested negative for the antibodies.

The study’s purpose was to determine whether the antibodies provide a reliable indication of prognosis. In ongoing trials, doctors are testing whether patients with HPV-associated cancers can be treated less aggressively — and hopefully with fewer negative side effects — than people with non-HPV-associated cancers, said senior author Karl Kelsey, professor of epidemiology, pathology, and laboratory medicine at Brown University. If trials prove successful, then it will be particularly important to determine whether cancers are HPV-associated.

“The assessment of a patient’s HPV status likely will affect treatment,” Kelsey said. “That’s why there’s real interest in getting it right; for instance, how do you test?” 

One exciting element of the study is the notion that testing could be done without invasive tissue sampling. 

“Our data indicates that assessing a patient’s immune response is likely sufficient for determining HPV-related clinical benefit, and in fact may be a superior method to determine HPV-benefit for particular patient subgroups,” said Nelson.

Better prognosis across the board

Prior studies have focused primarily on the detection of HPV virus in tumors located in the oropharynx — the area of the throat right behind the mouth. An important contribution of the current study is demonstrating HPV is likely important for all forms of head and neck cancer. Those patients with an HPV immune response with tumors located in the oropharynx and larynx had a similar risk of dying during the follow-up period, and benefit was slightly attenuated for those patients with tumors located in the oral cavity.

The clinical benefit associated with the immune response to HPV carried through for all patients, even if they consumed tobacco and alcohol. The authors note that those patients with a history of heavy smoking had the worst outcomes, particularly if they had no evidence of HPV infection. 

“An important message for head and neck cancer patients is the need to quit smoking to improve their cancer prognosis,” said Nelson. 

Relates to broader advances in immunity and cancer

Nelson said their group is designing new studies to evaluate whether other viruses elicit a similar immune response that impacts head and neck cancer outcomes. 

“Viral infections are known to impact an individual’s immune profile, and it is important to consider the possibility that other common viruses might be influencing cancer patient outcomes,” said Nelson.

The study findings might also be important for understanding why immunotherapy is particularly beneficial for certain subgroups of patients.

“Historically, HPV has only been considered an important factor for head and neck cancers that occur in the oropharynx,” said Nelson. “Our data indicate that measuring immune response to HPV may help better classify all head and neck cancer patients, and we are keen to understand if that immune status impacts response to specific therapies.”

If HPV-related cancers can be treated differently, Kelsey said, then serum-based testing to determine the role of the virus could soon be available, too.

In addition to Nelson and Kelsey, the paper’s other authors are Dr. Michale Pawlita, Dominique Michaud, Michael McClean, Scott Langevin and Melissa Eliot.

The study was funded by Minnesota Masonic Charities (to Nelson), the National Cancer Institute (grants: R01CA121147, R01CA100679, R01CA078609 to Kelsey), and the National Institutes of Environmental Health Sciences (T32ES07272 to Langevin).

Contact: Jennifer Hedtke, Masonic Cancer Center, 612.481.1575,

Masonic Cancer Center, University of Minnesota is a Comprehensive Cancer Center designated by the National Cancer Institute. For more than 25 years, researchers, educators, and care providers have worked to discover the causes, prevention, detection, and treatment of cancer and cancer-related disease. Learn more about the Masonic Cancer Center at