Infections with a Human Papillomavirus (HPV) cause 99% of cervical cancer cases, and the disease’s first sign is often the appearance of precancerous lesions on a woman’s cervix. But bacteria may play an important role, too. New research suggests that the cervical microbiome may influence HPV infection more than researchers previously thought.
In a study published this week in mBio, researchers used deep sequencing to identify bacterial families associated with the high-grade lesions that are more likely to become cancerous. The researchers found a richer and more diverse microbial mix within high-grade lesions than in low-grade lesions or healthy cervices.
“The data really speaks to the idea that these bacteria are present at the lesions,” Angeletti says. “But what is the relationship, and are they there in advance of the HPV?”
Understanding that relationship has clinical implications for cervical cancer, the second-most common cause of cancer death among women worldwide. If researchers do determine that bacteria facilitate the growth of the lesions, then pretreatment with certain antibiotics may prevent cancer from developing.
Angeletti and his colleagues sequenced 16s RNA genes in samples taken directly from cervical lesions of women in Tanzania, which has one of the highest cervical cancer mortality rates worldwide. The researchers first compared bacteria in samples from HIV-negative women to samples from HIV-positive women, as previous studies have suggested that HIV infection places a person at higher risk of HPV infection.
The analysis showed a larger variety of distinct taxa in samples from HIV-positive women than in samples from HIV-negative women. Additionally, in the subset of women who were HIV-positive and had cervical lesions, the researchers found that higher-grade lesions hosted more diverse populations of bacteria.
Of the bacteria identified, those belonging to the Mycoplasmatales family had the clearest correlation to the severity of lesions. On average, those bacteria were more abundant in the presence of higher-grade lesions and less abundant for lower-grade lesions. The researchers found the same relative relationships in both HIV-positive and HIV-negative women.
Aside from cervical cancer, HPV also raises a person’s risk of oral, anal, penile, and other cancers. “It works by affecting mucosa anywhere there is mucosal tissue,” says Angeletti. At those same sites, he says, the microbiome could play a role in promoting cancer—and might similarly suggest an avenue for future preventive treatment.