$7.8 million awarded to UB and partners to study influence of oral microbiome on cancer-linked oral thrush and HPV

BUFFALO, N.Y. – The National Institute of Dental and Craniofacial Research has awarded two grants totaling more than $7.8 million to the University at Buffalo, Roswell Park Comprehensive Cancer Center and Albert Einstein College of Medicine to explore the influence of the oral microbiome on both the risk of developing oral thrush during cancer treatment and the risk of infection with cancer-linked human papillomavirus (HPV) among people with HIV.

The projects are co-led by principal investigators Patricia Diaz, DDS, PhD, SUNY Empire Innovation Professor in the UB School of Dental Medicine and director of the UB Microbiome Center; and Nicolas Schlecht, PhD, professor of oncology at Roswell Park Comprehensive Cancer Center and research professor of epidemiology and environmental health in the UB School of Public Health and Health Professions. Robert D. Burk, MD, professor of pediatrics, microbiology and immunology, and epidemiology and population health at Albert Einstein College of Medicine and a member of the Cancer Epidemiology, Prevention and Control Program at Montefiore Einstein Cancer Center, is also a principal investigator on the project to investigate HPV-associated oral cancers.

“We are very excited about these newly funded clinical studies on oral infections and the microbiome,” says Diaz. “We expect these studies will reveal important information on how the oral microbiome interacts with opportunistic pathogens, whether it’s fungi like Candida or host-associated viruses like HPV.”

Finding the pathogenic partners of oral thrush

Funded by a five-year grant, this nearly $3.7 million award will support a study that aims to identify risk factors, including the oral microbiome, that contribute to susceptibility to oral thrush in chemotherapy recipients.

Oral thrush is a fungal infection of the mouth caused by the yeast Candida albicans. Up to 40% of chemotherapy recipients develop oral thrush, as the treatment damages the body’s mucous membranes and weakens the immune system, say the researchers. Past studies have also found that oral bacteria contribute to the severity of oral thrush.

The team will evaluate chemotherapy patients treated at Roswell Park Comprehensive Cancer Center prior to and throughout the progression of oral thrush to understand the role played by bacteria in hampering the body’s antifungal defenses and promoting infection. The researchers will develop a machine-learning model based on the oral microbiome and other risk factors to predict the incidence of oral thrush in chemotherapy recipients.

The results will reveal which species of bacteria act as pathogenic partners of Candida albicans, as well as guide the development of preventive and therapeutic interventions that could decrease antifungal use in chemotherapy recipients and improve quality of life in this population.

Other UB collaborators on this project include Mira Edgerton, DDS, PhD, research professor of oral biology in the UB School of Dental Medicine; and Yijun Sun, PhD, associate professor of microbiology and immunology in the Jacobs School of Medicine & Biomedical Sciences at UB.

Reducing the risk of HPV-related cancers

The rates of HPV-associated head and neck cancers are increasing at an alarming rate, particularly among people with HIV, according to the researchers. The composition of the oral microbiome is linked to increased susceptibility to oral HPV infection, and HIV is known to affect the makeup of the oral microbiome.

HPV is the most common sexually transmitted infection, according to the Centers for Disease Control and Prevention. Most infections cause no symptoms, however, some infections by high-risk types can persist for many years and in rare cases lead to oropharyngeal cancer.

Funded by a five-year, nearly $4.2 million award, the researchers aim to examine if bacterial and fungal commensal infections in the mouth impact the persistence of oral HPV infections in people living with HIV. They hypothesize that microbes residing in the mouths of people living with HIV may increase inflammation and dysregulate the immunity and integrity of the oral mucous membrane, enabling high-risk HPV types to persist.

The study will analyze data and samples from the MACS-WIHS Combined Cohort Study, the largest HIV cohort study in the United States. The results may lead to innovative approaches to reduce the risks of HPV-associated head and neck cancers.