Researchers at the University of Arizona (UA) have completed the first-of-its-kind study that could aid in the treatment, diagnosis, and prevention of cervical cancer by identifying cervicovaginal metabolic signatures, or “fingerprints,” that distinguish patients with human papillomavirus (HPV), pre-cancerous cervical conditions, and cancer.

An interdisciplinary team led by Melissa Herbst-Kralovetz, associate professor at the UA College of Medicine–Phoenix, identified three compounds that distinguish cervical cancer patients from healthy women. The study, “Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal profiling” was published online April 24 in EBioMedicine.

“This study is an example of how scientific research and breakthroughs directly impact patient care,” said Dr. William Cance, deputy director of the UA Cancer Center. “Dr. Herbst-Kralovetz, also a researcher at the UA Cancer Center, and her colleagues have employed novel biologic analyses to identify metabolic fingerprints that could be used to develop future diagnostics, interventions, or therapies for cervical cancer.”

The research team integrated cutting-edge analyses including metabolomics to reveal new information about how viruses, bacteria, inflammation, and disease impact metabolic signatures. Metabolomics is the comprehensive study of the metabolome, the collection of biochemicals, or metabolites, present in cells, tissues, or body fluids. Levels of metabolites often change in response to disease.

This is the first report on cervicovaginal metabolomes in HPV-associated precancerous cervical conditions and cancer that demonstrates the predictive value of metabolic fingerprinting in abnormal cell metabolism. The study identified 475 metabolites in cervicovaginal samples that changed across progression of disease, resulting in unique metabolic fingerprints.

The fingerprints identified in the study helped distinguish women with HPV, precancerous conditions, or cervical cancer from those who were HPV negative.

“Metabolic fingerprinting has the potential to be used for the development of future diagnostics, preventatives, or treatments for cervical cancer to enhance women’s health outcomes here in Arizona and beyond,” said Herbst-Kralovetz, who also is director of the Women’s Health Microbiome Initiative at the College of Medicine–Phoenix. “Doing so could aid in reducing mortality to the fourth-leading cause of cancer in women.”

When compared with women who were HPV-negative, women diagnosed with invasive cervical cancer were highly associated with genital inflammation and a higher vaginal pH. In precancerous groups, researchers observed how microbial communities influenced amino acid and nucleotide metabolisms, which are building blocks of cells.

A novel aspect of the study revealed how specific metabolites were associated with different vaginal bacterial communities as well as levels of genital inflammation. An increase in health-associated Lactobacillus correlated with high levels of anti-inflammatory nucleotides. Collectively, they revealed that specific features of the reproductive tract’s microenvironment—HPV infection, genital inflammation, and vaginal bacteria —profoundly impact cervicovaginal metabolomes.

“Cervical cancer is a devastating disease, especially in rural areas and developing countries,” said Jennifer Barton, director of the UA BIO5 Institute. “These findings could lead to a simple, rapid diagnostic test to help women get the treatment they need.”

Virtually all cervical cancers are caused by HPV, a common sexually transmitted infection that nearly every sexually active person catches. According to the Centers for Disease Control and Prevention, HPV is thought to be responsible for 90% of cervical cancers, and about 24,400 HPV-associated cancers occur in women each year.

“Our ultimate goal is to integrate the clinical and molecular data to identify patients at risk for progressing to cancer to pinpoint potential targets for prevention or for tracking disease progression,” Herbst-Kralovetz said.

Herbst-Kralovetz said they plan to expand the study to a larger population in Arizona, adding that the team has ongoing studies to investigate the relationship of genital microbiota to other gynecologic cancers, including endometrial cancer.

The research was made possible through the financial support of the Banner Foundation in Obstetrics and Gynecology and from the Flinn Foundation Grant No. 1974.