# Schistosoma haematobium infection is associated with oncogenic gene expression in Cervical Mucosa, with enhanced effects following treatment: A pilot study

## TL;DR

This study found that Schistosoma haematobium infection and its treatment may alter cervical gene expression linked to cancer, suggesting a potential increased risk of cervical cancer.

## Contribution

The study is the first to show that S. haematobium infection and post-treatment clearance are associated with oncogenic gene expression changes in cervical mucosa.

## Key findings

- Women with S. haematobium infection showed 9 differentially expressed genes linked to oncogenesis.
- Post-treatment parasitological clearance was associated with 29 altered genes, many related to cancer pathways.
- Gene expression changes were more pronounced after treatment compared to active infection.

## Abstract

Schistosoma haematobium is a parasitic worm that infects over 110 million people worldwide, laying eggs that migrate into host urinary and reproductive tracts. While S. haematobium is a known carcinogen in the urinary bladder, its role in cervical cancer remains unclear and molecular effects of parasite eggs in genital tissue are largely unknown. Our objective was to characterize cervical transcriptional profiles in women with or without active S. haematobium infection and after anti-schistosome treatment.

We collected cervical cytobrush samples from women living in areas of Tanzania endemic for S. haematobium, before and 4–12 months after praziquantel treatment, and extracted RNA for transcriptome analysis. mRNA was isolated using poly(A) selection and sequencing was performed on an Illumina Hi-Seq4000 platform. Transcript alignment to the human hg19 reference genome and counting were accomplished using the HTSeq package. Genes were assessed for differential expression using DESeq2 and Limma. Ingenuity Pathway Analysis (IPA) was employed to identify gene networks altered in the presence of S. haematobium infection and following parasitological elimination of infection.

As part of this pilot study, we enrolled 20 participants with and 19 without S. haematobium infection. After adjusting for multiple comparisons, we identified 9 differentially expressed genes in women with versus without infection at baseline, 23 in women with parasitological clearance of infection post-treatment versus with infection at baseline, and 29 in those with parasitological elimination of infection versus without infection at baseline. Most differentially expressed genes were associated with heightened oncogenesis in both women with infection and in those with parasitological clearance of infection after treatment. Using IPA, we identified cancer-related networks and pathways in women with parasitological clearance compared to women with and without infection, as well as pathways involving inflammation and compromised epithelial integrity.

Women with S. haematobium infection and those with recent parasitological clearance were found to have cervical gene alterations that have been reported in various cancers. Our findings suggest a possible increase in cervical cancer risk and susceptibility to secondary infections shortly after treatment. Further research is necessary to ascertain whether altered gene expression after parasitological clearance of S. haematobium resolves over time.

Schistosoma haematobium is a parasitic worm that infects millions globally, mostly in Africa. While its association with bladder cancer is well-documented, its role in cervical cancer is debated. Data on cervical mucosal gene expression in women with this infection are limited. We analyzed cervical transcriptional profiles in women with and without active S. haematobium infection, and longitudinally assessed the impact of anti-schistosome praziquantel treatment. Women from Tanzanian villages where S. haematobium is highly prevalent were enrolled. RNA was extracted from cervical cytobrush samples, followed by mRNA isolation and sequencing. Gene expression was analyzed using DESeq2, Limma, and pathway analysis tools. Among our cohort of women, differential expression analysis revealed 9 genes in women with versus without S. haematobium infection, 23 in women who had parasitological clearance of infection versus women with S. haematobium infection, and 29 in women who had parasitological clearance of infection versus women without S. haematobium infection. Most genes had roles in oncogenesis. IPA identified networks and pathways related to cancer and inflammation in women with parasitological clearance compared to women with and without S. haematobium infection. In women with S. haematobium infection, alterations were observed in cervical mucosal gene expression that have been previously associated with oncogenesis. Gene expression was even more profoundly altered in women who had been recently treated and experienced parasitological clearance.