Cervico-Vaginal Microbiome Dynamics Across HPV-Driven Lesion Stages in Moroccan Women

Cervical cancer (CC), often caused by persistent high-risk HPV infection, is a major health issue for Moroccan women. This study is the first in Morocco to examine how the cervico-vaginal microbiome differs across HPV-related clinical stages. Using 16S rRNA sequencing, the researchers analyzed samples from 247 women-100 healthy controls, 43 hr-HPV⁺ pre-cancer cases, and 104 post-treatment CC cases. In healthy women, Lactobacillus dominated (70%), but it significantly declined in the pre-cancer group (45%, p < 0.01) and remained low post-treatment (50%). Meanwhile, Pseudomonadota and Actinobacteriota increased in pre-cancer samples (up to 25-30%, p < 0.01). Although the alpha diversity remained stable, the beta diversity differed significantly across stages (p = 0.001), but not by HPV status. Post-treatment samples showed a sharp decline in Bacillota (logFC -5, p < 10^-15) and increases in Campylobacterota and Fusobacteriota (logFC +6 to +21, p < 10^-16). Functionally, chemo-heterotrophy and fermentation declined, while nitrogen fixation and phototrophy rose in pre-cancer cases. Host factors like late menarche, high parity, STIs, and contraceptive use correlated with specific microbiota shifts.