GILLISON

For Researcher Maura Gillison, the human papilloma virus was a smoking gun. After proving that the virus was present in tumor cells of a subset of patients with head and neck cancer—primarily those of the pharynx, tonsils, and base of tongue and often those who didn't fit the risk profile for the disease—she set out to find how it could affect screening, prognosis, and treatment of head and neck cancers.

Gillison was an assistant professor of oncology at the Kimmel Cancer Center in 2002. She was intrigued by evidence of human papillomavirus (HPV) DNA in head and neck and cancer wanted to find out what role the virus might be playing in this form of cancer. The fact that the virus had been detected in some head and neck cancer was no secret, but most scientists attributed it to laboratory contamination.

SHAH

“ I couldn't help but wonder what if it wasn't,” she said.

When she began her research, Gillison truly expected the results to be negative, that she would not find HPV in the tumor cells. Instead, she became the first researcher to prove that the virus was actually driving the cancer. To her surprise, she also found that these patients typically fared better than those with non-HPV-associated head and neck tumors.

The finding presented opportunity for intervention, such as early detection of HPV infection through screening and potential prevention of the infection through HPV vaccines, then just recently approved for the prevention of cervical cancers, the majority of which are also caused by HPV infection. HPV-positive cancers made up about 60% of cancers of pharynx, tonsils and base of tongue, and those who go them were cured 85% of the time.

D'SOUZA

Her findings shifted the treatment paradigm for this cancer, and today distinguishing head and neck cancers between HPV-positive and negative to guide treatment is standard of care.

“It suggests that HPV-positive head and neck cancers comprise a distinct molecular, clinical, and pathological disease very different from other types of the disease,” said Gillison.

She suspected the HPV infection of the oral airway occurred through oral/genital contact. She set out to find exposures contributing to HPV-related oral cancers. She was particularly, interested in tonsillar cancers , which had been steadily rising since 1973.

In May 2007, Gillison’s practice-changing research was published in the prestigious New England Journal of Medicine, with a finding that the overriding risk factor for the cancer was multiple sex partners

Gillison collected blood samples and examined a variety of behaviors, including smoking, alcohol use, family history, poor oral hygiene, multiple sex partners, and other sexual behaviors that would expose a person to or HPV. She followed participant for five years and found that people who reported more than six oral sex partners through a confidential survey had a higher than eight-fold increased risk of developing cancer.

“When you compare that to three-fold for smoking and two-fold for drinking, this is a very significant odds ratio,” said Gillison.

In 2007, the American Society of Clinical Oncology named Gillison’s research one of the top cancer advances of the year.

Gillison is now a professor in the department of Thoracic/Head and Neck Cancer at M.D. Anderson Cancer Center, but Amber D’Souza, Ph.D., Kimmel Cancer Center and Bloomberg School of Public Health researcher, who was mentored by Gillison, has built upon the research.

FAKHRY

D’Souza is working with Carole Fakhry, director of the Johns Hopkins Head and Neck Cancer Center to better understand the natural history of HPV infections, how long they last, and risk factors that make them persist.

It is the persistence, because most people naturally clear the infection.

“It’s not so much the infection, but the clearing of the infection that is the problem,” says D’Souza. “Overall, the cancer risk is low.

This aspect of the research, she says, has been in reassuring patients with HPV-positive head and neck cancers worried about putting their partners at risk. D'Souza's multicenter, pilot study revealed that spouses and long-term partners of patients with mouth and throat cancers related to infection with the human papilloma virus (HPV) appear to have no increased prevalence of oral HPV infections.

In terms of screening, they are working on screening tests that can

“There are lots of people who have risk factors who don’t get cancer and vice versa, so HPV alone is not very predictive as a biomarker for cancer risk, and that makes screening challenging,” she says. “Screening people who have no symptoms risks overtreatment and causing more harm than good in someone who test positive for HPV, but were never going to get cancer.”

They continue to work on ways to screen for those most at risk of developing cancer, but there is work to be done in this area, D’Souza says.

They are also interested in better understanding which patients are likely to develop treatment-resistant cancers. Despite the higher survival rates for patients with HPV-positive head and neck cancers, D’Souza says, not every patient does well.

“We are trying to better stratify and understand the nuances of our patient population,” she says.

Vaccines, like Gardacil, perhaps provide the greatest with the opportunity to prevent HPV infection, and as a result, the development of HPV-related cancers.

She suspects there are a small number of cancers being prevented in young people in their 30’s now as a result of the vaccine, but with the median age of cancer 65, the good news is coming in about ten years.

“Better uptake of the vaccine would help, but I am confident prevention is going to have a significant impact,” she says.