Researchers identify key bacteria in Latina study participants’ cervicovaginal microbiome linked to HPV and cervical cancer

Latina women experience disproportionately higher rates of human papillomavirus called HPV, precancerous cervical cell growth called dysplasia and cervical cancer compared to other racial and ethnic groups.

After completing a systematic review, University of Arizona researchers found 42 unique bacteria in the cervical and vaginal microbiome of 131 premenopausal Latina women in 10 countries. From those results, they found 16 bacteria with HPV, 24 unique bacteria with abnormal cytology or dysplasia, and five bacteria that are connected to cervical cancer.

“Our studies and this systematic review suggest that persistence and cancer is influenced by specific vaginal bacteria,” said lead researcher Melissa Herbst-Kralovetz, PhD. “There were seven bacteria that were consistently reported across studies, and that gives us insights on what to focus on moving forward.”

They published their findings in the Journal of Epidemiology and Global Health that research into cervical and vaginal microbiome is crucial to better understanding the role of the microbiome in HPV infection, cervical dysplasia and cervical cancer worldwide, especially in Latina women.

According to Herbst-Kralovetz, professor of basic medical sciences in the University of Arizona College of Medicine – Phoenix and director of the Translational Women’s Health Research Program on the medical campus, their research addresses important health disparities in this historically understudied, underrepresented and underreported population of women.

Postdoctoral researcher Nicole Jimenez, PhD, BIO5 Institute postdoctoral research associate in the Herbs-Kralovetz lab and department of obstetrics and gynecology, said that since Hispanic individuals are 40% more likely to be diagnosed with cervical cancer than non-Hispanic white individuals, the researchers sought to find out if these same trends from previous systematic reviews were comparable in Hispanic populations or if other patterns would emerge.  

“We found that there are similar trends of dysbiotic bacteria that are more prevalent or abundant in HPV infection and malignant disease,” Jimenez said. “However, what was most notable to me was that there are not many studies being conducted on HPV or cervical cancer and the microbiome in Hispanic populations.” 

Their goal is to better inform cervical cancer prevention strategies in Latina women.

“I think one of our important findings was a call to action for future robust and standardized investigation in this area and to include not just race and ethnicity characteristics but also sociocultural factors as well,” she said.

Connecting a systematic study to earlier work

Every year about 14,000 women are diagnosed with cervical cancer in the United States and more than 4,000 women die from it. Human papillomavirus is almost always the cause of cervical cancer.

Herbst-Kralovetz said her team has been working on the vaginal microbiome and its influence in HPV progression to cancer for about 14 years. 

“Most HPV infections are cleared [from the vagina with] no problem. About 90% of people who get exposed to HPV clear it,” she said. “That other 10% has persistent HPV infection that may develop into dysplasia and ultimately cancer.”

She said about 12 years ago, she embarked on clinical study with clinical collaborator, Dana Chase, MD, now at the University of California, Los Angeles.

After starting with the microbiome, they wanted to learn more about the cervicovaginal microenvironment and its influence in promoting HPV. From a cohort of equal Caucasian and Hispanic women, Herbst-Kralovetz said they were able to produce seven publications.

Together with other researchers, they analyzed multiple "omics" datasets to develop predictive models of the cervicovaginal microenvironment and identify characteristic features of vaginal microbiome, genital inflammation and disease status.

“We knew that there were specific bacteria in our initial cohort that were associated with Hispanic ethnicity as well as HPV infection and progression to cancer,” she said of the results that prompted the latest systematic study.

Creating a publication to examine Latina women, HPV, and cervical cancer worldwide 

First author Vianney Mancilla, a post-baccalaureate student, joined the Herbst-Kralovetz Lab at the start of the COVID-19 pandemic through the Frontera BLAISER (Border Latino and American Indian Summer Exposure to Research) program to pursue her interest in minority and women’s health. The Frontera BLAISER program is designed for underrepresented undergraduates to prepare them for medical school.

“As an undergrad, it's really an incredible opportunity to be working with the University of Arizona College of Medicine - Phoenix, especially with it being my one of my number one school [in applying to medical school],” Mancilla said. “I'm very thankful for Dr. Herbst-Kralovetz and the lab for allowing me to pursue what I was interested in while also delving deeper into their Latina study population.”

What started as a summer research project for Mancilla’s Frontera BLAISER project quickly evolved into a worldwide systematic review with the collaboration of Melissa Flores, PhD, assistant clinical professor, UArizona Department of Psychology and director of the Health Equity Analytics Lab (HEAL) and Naomi Bishop, associate librarian at the University of Arizona College of Medicine - Phoenix.

“We brought them in for their expertise,” Herbst-Kralovetz said of Dr. Flores and Bishop. “It's been a great team to work with over the time we conducted this systematic review. And Naomi as our medical librarian was an integral team member to facilitate that process.”

Herbst-Kralovetz said there were a couple systematic studies already published on the connection between lactobacilli dominance and HPV infection connection, though they were primarily conducted with people who were from European ancestry.

Working with Bishop, the researchers narrowed their results to 25 articles from two databases from January 2000 through November 11, 2022. After searching hundreds of articles, they found only 10 countries that had published on Latinas and the cervical vaginal microbiome and cervical carcinogenesis. 

Future plans

The group’s next step is to take the results from the systematic review and apply them to their earlier work to see if there's specific microbial signatures in the microenvironment that may indicate why they are promoting cervical cancer. 

“The vaginal bacteria that we consistently identified [in the publication] across studies give us insights on where to go next,” Herbst-Kralovetz said.