Characterisation of the Microbiome-Immune Interface in Cervical Carcinogenesis Among HPV-Positive Nigerian Women: A Multi-Omics Investigation

Human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, with the cervical microbiome increasingly recognised as a co-factor modulating immune surveillance and progression from HPV infection to invasive cancer. This dissertation investigates the microbiome-immune interface in cervical carcinogenesis among HPV-positive Nigerian women through a multi-omics design. A case-control study enrolled 240 HPV-positive women across three groups: normal cervical cytology (n=80), cervical intraepithelial neoplasia grade 2 or above (n=80), and invasive cervical cancer (n=80) at teaching hospitals in Lagos (South West), Port Harcourt (South South), and Kano (North West). Cervical swabs underwent 16S rRNA gene amplicon sequencing for microbiome characterisation, and cervical biopsies were processed for RNA-seq transcriptomic analysis of immune pathway gene expression. Metabolomic profiling of cervical lavage by untargeted LC-MS/MS was also performed. Lactobacillus iners-dominated cervicotypes were significantly more prevalent in the CIN2+ and cancer groups compared to Lactobacillus crispatus-dominated communities in normal cytology. Loss of Lactobacillus dominance correlated with upregulation of IL-17 and TGF-beta pathway genes and downregulation of CD8+ T-cell cytotoxic signatures in transcriptomic data. Metabolomic analysis identified putrescine and cadaverine accumulation in cancer-associated microbiomes. A multi-omics integration model discriminated cancer from CIN with AUC of 0.93. The dissertation provides the first Nigerian multi-omics characterisation of cervical microbiome-immune crosstalk and advances mechanistic understanding of African-population cervical carcinogenesis. Keywords: cervical cancer, microbiome, HPV, multi-omics, Nigeria