Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion.

Abstract

Human papillomavirus (HPV) infection is associated with the vast majority of cervical cancer cases as well as with other anogenital cancers. PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions. The present study was performed to test whether the cervical microbiome influences vaccine responses and to explore host factors as determinants of the cervical microbiome composition in women with biopsy-proven high-grade squamous intraepithelial lesions. In a recently completed Phase I clinical trial of PepCan, histological response rate of 45% (14 of 31 patients), a significant increase in circulating T-helper type 1 cells, and a significant decrease in HPV 16 viral load were reported. DNA, extracted from liquid cytology specimens collected before and after vaccinations, were amplified and then hybridized to a G4 PhyloChip assay to characterize the microbiome. We describe trends that certain bacterial taxa in the cervix may be enriched in non-responders in comparison to responders (Padj = .052 for phylum Caldithrix and Padj = .059 for phylum Nitrospirae). There was no difference in bacterial diversity between the 2 groups. A permutational analysis of variance performed for various demographic and immune parameters showed significant clustering with microbiome beta diversity for race, HPV 16 status, peripheral T-helper type 1 cells, and HLA-B40 (P = .001, .014, .037, and .024, respectively). Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines.

• Authors: Rahul Ravilla, Hannah N Coleman, Cheryl-Emiliane Chow, Luisa Chan, Barbara J Fuhrman, William W Greenfield, Michael Scott Robeson, Kathryn Iverson, Horace Spencer 3rd, Mayumi Nakagawa
• Journal: Integrative cancer therapies (Integr Cancer Ther) 2019 Jan-Dec Vol. 18 Pg. 1534735419893063 ISSN: 1552-695X [Electronic] United States
• PMID: 31833799 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Papillomavirus Vaccines

Topics

• Adult
• Cervix Uteri (immunology, microbiology)
• Female
• Human papillomavirus 16 (immunology)
• Humans
• Microbiota (immunology)
• Middle Aged
• Papillomavirus Infections (immunology, microbiology)
• Papillomavirus Vaccines (immunology)
• Squamous Intraepithelial Lesions (immunology, microbiology)
• Uterine Cervical Neoplasms (immunology, microbiology)
• Viral Load (immunology)
• Young Adult