September 21, 2020

New study suggests vaginal microbiome may play a role in high-risk HPV, cervical cancer

The results of a vaginal microbiome study conducted by University of Michigan, Penn State, and Ohio State researchers led by Kim McKee could help identify women with high-risk HPV, which is strongly associated with the development and progression of cervical cancer.

Kimberly McKee PhD MPH
Kimberly McKee, Ph.D., lead author

Researchers have published a population-based study that examines the vaginal microbiota in a stratified, random sample of woman residing in Appalachian Ohio and West Virginia, which as a region has the nation’s highest annual rate of cervical cancer mortality.

Previous research has shown that different types of vaginal microorganisms may be associated with Human Papillomavirus (HPV) persistence over time and is a factor that could provide insight into cervical cancer progression, either as a risk marker or risk mediator. Persistent infection with a high-risk HPV is strongly associated with the development and progression of cervical cancer over many years.

It is estimated that more than half a million women die of cervical cancer globally each year, according to organizations including GLOBOCAN (a global cancer database), the World Health Organization, and the Centers for Disease Control and Prevention and National Cancer Institute.

The study, led by Kimberly McKee, Ph.D., M.P.H., assistant professor, published recently in Gynecology and Pelvic Medicine, used Illumina MiSeq genomic sequencing to analyze and characterize the vaginal microbiota of women in rural Appalachia. Researchers sequenced 16S rRNA gene amplicons from cytology (cellular) samples of 308 participants in the Community Access, Resources and Education (CARE): Project 3 study, which recruited women across 16 clinics in southeast Ohio and West Virginia. Barbara Reed, M.D., M.S.P.H., professor emeritus, and Diane Harper, M.D., M.P.H., M.S., professor, both in Family Medicine, were also study-co-authors. The team randomly selected three groups of CARE 3 participants:

  • Women with abnormal cytology regardless of whether they had HPV or not.
  • Women with high-risk HPV but no abnormal cytology.
  • Women with neither abnormal cytology nor HPV infections.

The study broadens research already conducted on women in Appalachia by using a large and unique sample size of high-risk women; utilizing molecular methods to characterize vaginal microbiota; and adjusting for different patient characteristics.

Compared to women without cytologic abnormalities, the vaginal microbiota of women with abnormal cervical cytology and women with high-risk HPV-positive status was characterized by a high and diverse abundance of bacteria present as bacterial vaginosis (Gardnerella vaginalis) and a reduced amount of Lactobacillus gasseri, which is one hallmark of a healthy vaginal microbiota. Smoking, having two or more sexual partners in the past year, lack of condom use, and age were significantly associated with high-risk HPV and abnormal cervical cytology. However, after adjusting for these factors, these differences were reduced.

“Vaginal microbiota may confer a range of health effects dependent on bacterial community composition that are protective,” the authors write. “However, it is equally possible that vaginal microbiota, in concert with HPV, can influence oncogenesis (the development of cancer).

“Our results extend the current understanding of altered vaginal microbiota among high-risk women by identifying community types and specific taxa (or microbes) with cervical disease,” they add.

The researchers note that study limitations include its cross-sectional design and the fact that information about the grade of cervical intraepithelial neoplasia (CIN), and whether or not the HPV was a persistent infection, was not available. Additionally, given that there was some heterogeneity within comparison groups, the results are “likely underestimates of the association between aberrant vaginal microbiota and HPV infection,” according to the researchers.

“While our data cannot establish a (causal link between) the vaginal microbiota in cervical intraepithelial neoplasia (CIN) and high-risk HPV, it suggests that vaginal communities that are Lactobacillus-depleted may help to identify women at higher risk of HPV acquisition and persistence leading to abnormal cervical cytology – i.e. vaginal microbiota signatures may be risk markers even if they are not causally related to CIN,” they write.

To be of use for prognostic use, the authors recommend further study and validation of the observed associations between high-risk vaginal microbiota, CIN and high-risk HPV.

Article citation: Mckee KS, Carter KA, Bassis C, et al. The vaginal microbiota, high-risk human papillomavirus infection, and cervical cytology: results from a population-based study. Gynecology and Pelvic Medicine. 2020;3:18-18. doi: 10.21037/gpm-20-10.

READ ALSO: New Research Looks at Link Between Diet, Cancer Prevention, and the Microbiome
READ ALSO: Combining HPV vaccination with screening to prevent cervical cancer