A team of Brazilian researchers have discovered that a common oral bacterium Fusobacterium nucleatum (Fn), can also be found within tumors of patients with head and neck cancer and can be a prognostic indicator of longer survival among patient with the disease. The study, published in the Journal of Oral Microbiology, showed that patients with intratumoral Fn had survival rates nearly 67% longer (60 months vs. 36 months) than those patients whose tumors were without the bacterium.
The intratumoral presence of Fn was unexpected. “If we analyze a person’s saliva, we’re likely to find this bacterium since it’s normally present in the oral cavity and makes up the dental biofilm. What we didn’t expect, however, was for it to be located within the tumor microenvironment,” said senior author Rui Manuel Reis, PhD, scientific director of the Teaching and Research Institute at Hospital de Amor.
For their research, the team analyzed 94 archived tumor samples from patients with head and neck carcinoma (HNC) treated at Hospital de Amor, São Paulo. Their method used droplet digital PCR (ddPCR), a highly sensitive molecular technique, to detect traces of Fn DNA in formalin-fixed, paraffin-embedded (FFPE) tumor tissues, samples typically considered too degraded for such precision.
“Using more traditional methodologies, it’d be difficult to identify the presence of this bacterium with the same precision in degraded material such as paraffin,” said Reis. “However, the ultra-sensitive PCR technique offers high reliability and sensitivity—even minimal traces of bacterial DNA can be detected.”
This analysis identified Fn in 59.6% of tumor samples, with a higher frequency in oropharyngeal tumors (62.1%) than in tumors of the oral cavity (53.6%). The longitudinal study followed researchers over five years and found that those whose tumors contained Fn had significantly longer survival—60 months on average—compared to 36 months for those without the bacterium.
“We didn’t expect this result because, in other types of cancer such as colorectal cancer, the presence of these bacteria is usually associated with greater aggressiveness and lower survival,” said Reis.
The study also sought to discover whether the presence of Fn was associated with known prognostic biomarkers such as Human Papillomavirus (HPV) status and telomerase reverse transcriptase promoter (TERTp) mutations, but found no significant associations.
The biological mechanism by which Fn might contribute to improved outcomes remains unclear. One possibility is that its presence may activate immune responses within the tumor microenvironment. “Fn might induce a localized immune response that could paradoxically enhance anti-tumor immunity in certain contexts, leading to improved survival,” the researchers wrote.
The investigators said one of the strengths their research was their ability to use a species-specific ddPCR assay, which allowed accurate detection of Fn DNA even in older, archived tissue. This could be potentially important for the development of clinical diagnostics, since archived samples are often the only material available for study.
“We showed that even using old material and in small quantities, we were able to detect this bacterium,” Reis said. “In other words, if it’s validated as a biomarker in the future, we already have an effective technique for identifying it in tumor tissue.”
If validated, Fn could become a prognostic biomarker and which could influence treatment strategies for head and neck cancers. As Reis noted: “This bacterium is emerging as an important modulator in the context of cancer and could solidify the use of the term ‘oncobacterium.’ If proven to be involved in the origin of cancer, antibiotics could be considered a complementary therapy to chemotherapy and radiotherapy.”
