Abstract 3267: Cervical microbiota and the urinary metabolome in patients with high-risk and low-risk HPV infections

Abstract

Abstract Genital human papillomavirus (HPV) is the world's most commonly diagnosed sexually transmitted infection, and high-risk HPV types are strongly linked to cervical dysplasia and carcinoma. The microbiota of the human cervico-vaginal tract is the interface between the host and environment, and its constituents may act as determinants of susceptibility for HPV infection. There exists the potential for reliable diagnostic biomarkers for cervical cancer in the cervical microbiome as well as in urine, which would be an important biospecimen due to its abundance and non-invasive collection strategy. In this study, we performed comprehensive metabolomic analysis on urine samples from 65 women (54 HPV+, 38 of whom have cervical intraepithelial neoplasia (CIN), and 11 HPV-) and discuss the potential diagnostic implication and metabolic description of high-risk and low-risk HPV infected patients. The experimental procedure employed gas chromatography mass spectrometry (GC-MS) on the urine-derived products and HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. We further characterized resident cervical bacteria in these patients using Illumina sequencing of the V4 region of the 16S ribosomal RNA with a high-resolution bioinformatics methodology (Resphera Insight v2.2) for species-level taxonomic assignment. The hybridization assay detected 11 low-risk and 10 high-risk HPV types many of them co-occurring in the cervical samples. Lactobacillus iners OTUs were shared by all samples but were significantly more dominant in women with low-risk HPV strains (p-value=0.05), while G. vaginalis, S. sanguinegens and L. jensenii were associated with high-risk strains. CIN1 and CIN3 dysplasic biopsies, detected significant enrichments of Gardnerella vaginalis, L.crispatus and Prevotella amnii (p-values <0.05). Preliminary GC-MS analysis identified elevated levels of palmitic (C16:0) and stearic fatty acids (C18:0) as well as lactic acid, abundant in the HPV+ samples while 5-oxo-proline and Neu5Ac (N-Acetylneuraminic acid) were abundant in the HPV- samples. Our preliminary data identifies possible microbial and metabolic biomarkers associated with oncogenic HPV and cervical intraepithelial neoplasia in women living in Puerto Rico. Citation Format: Gilmary Ortiz, Natalyia Chorna, Josefina Romaguera-Agrait, Magaly Martinez-Ferrer, Maria Sanchez, Ana P. Ortiz, Rafael Guerrero-Preston, James R. White, Filipa Godoy-Vitorino. Cervical microbiota and the urinary metabolome in patients with high-risk and low-risk HPV infections [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3267.