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Human papillomavirus (HPV) infections are responsible for 99% of cervical cancer cases, and the first sign of the disease is often the appearance of precancerous lesions on the cervix of the uterus. But bacteria can also play an important role. New research suggests that the cervical microbiome could further influence HPV infection than previously thought.
In a study published this week in mbio, the researchers used deep sequencing to identify the bacterial families badociated with high-grade lesions most likely to become cancerous. The researchers found a richer and more varied microbial mixture in high grade lesions than in low grade lesions or a healthy cervix. Mycoplasmatales, Pseudomonadales and Staphylococcus are the most abundant taxa badociated with the most serious lesions.
The data suggests that the Mycoplasma bacterium, in particular, could contribute to the growth of HPV-related lesions, says virologist and researcher Peter C. Angeletti of the University of Nebraska-Lincoln.
The new study found a clear correlation between the bacteria and the lesions, says Angeletti, but it is unclear which is the motor of the connection. "The data really suggest that these bacteria are present in the lesions," he explains. "But what is the relationship, and are they there before HPV?"
Understanding this relationship has clinical implications for cervical cancer, the second leading cause of cancer death among women worldwide. "This brings us to a road that talks about treatment," says Angeletti. If the researchers determine that the bacteria facilitate the growth of the lesions, for example, pretreatment with certain antibiotics may prevent the development of the cancer.
Angeletti and his colleagues sequenced the 16S RNA genes in samples taken directly from cervical lesions of 144 women in Tanzania, where the cervical cancer mortality rate is 39%. one of the highest in the world. Researchers first compared bacteria in samples of HIV-negative women to samples of HIV-positive women. Previous studies have suggested that HIV infection exposes a person to a higher risk of HPV infection.
The badysis showed a greater variety of distinct taxa in samples of HIV-positive women than in samples of HIV-negative women. In addition, in the subgroup of HIV-positive women with cervical lesions, the researchers found that higher-grade lesions harbored more diverse populations of bacteria.
Among the identified bacteria, those belonging to the Mycoplasmatales family had the clearest correlation with the severity of the lesions. On average, these 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 among HIV-positive women and HIV-negative women.
Angeletti says his next challenge is to establish the mechanistic relationship between bacterial fauna and HPV. The bacteria could directly or indirectly promote HPV infection by causing chronic inflammation, which promotes HPV.
Cervical cancer is the most common cancer caused by HPV, but the infection also increases the risk of cancers of the mouth, anus, penis and others. "It works by affecting the mucosa wherever there is mucous tissue," says Angeletti. On these same sites, he says, the microbiome could play a role in promoting cancer – and could also suggest a possibility of future preventive treatment.
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Material provided by American Society of Microbiology. Note: Content can be changed for style and length.
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