Table 1.

Summary of articles discussing the microbiome and HPV gynecologic cancer

Author	Participants	Microbial Analysis	Key Bacterial Organisms	Comments
Studies on the Cervicovaginal Microbiome and CIN
Guijon et al26	CIN positive (n = 106) Control (n = 79)	Culture, gram staining	Mycoplasma hominis	HPV, abnormal vaginal flora, and M. hominis, significantly associated with CIN.
Piyathilake et al34	CIN3 (n = 132) CIN2 (n = 208) CIN1 (n = 90)	V4 16S rRNA	Lactobacillus iners	α-and β-diversity was not significantly associated with disease status. L. iners abundance was associated with increased disease severity.
Klein et al35	LSIL (n = 72) HSIL (n = 50) Control (n = 23)	V4 16S rRNA	Mycoplasmatales, Pseudomonadales, Fusobacteria, Staphylococcus	Increased α-diversity was associated with HSIL and HPV. Brush samples from HSIL patients revealed unique associations with Mycoplasmatales, Pseudomonadales, and Staphylococcus.
Studies on the Cervicovaginal Microbiome, CIN, and Cervical Cancer
Mitra et al33	LSIL (n = 52) HSIL (n = 92) CC (n = 5) Control (n = 20)	V1-V2 16S rRNA	Lactobacillus spp., Lactobacillus crispatus, Sneathia sanguinegens	Lactobacillus depletion, high diversity and species richness was associated with increasing disease severity and high-risk HPV positivity.
Mitra et al32	CIN2 (n = 87)	V1-V2 16S rRNA	Lactobacillus spp., Megasphaera, Prevotella timonensis, Gardnerella vaginalis	Lactobacillus-dominant microbiome at baseline is more likely to have regression of CIN2 at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis, and Gardnerella vaginalis are associated with CIN2 persistence and slower regression.
Audirac-Chalifour et al37	HPV− control (n = 10) HPV+ control (n = 10) SIL HPV+ (n = 4) CC HPV+ (n = 8)	V3-V4 16S rRNA	Lactobacillus iners, Sneathia spp., Fusobacterium spp.	Increased α-diversity in CC and SIL with unique β-diversities at every stage of CC. All four study groups were dominated by a single distinct population of bacteria: L. crispatus, L. iners, Sneathia spp., and Fusobacterium spp. were dominant in HPV-negative samples, HPV-positive samples, SIL samples, and CC samples, respectively.
Łaniewski et al36	Control (n = 51) LSIL (n = 12) HSIL (n = 27) CC (n = 10)	V4 16S rRNA	Lactobacillus spp., Sneathia spp.	Decreased abundance of Lactobacillus spp. and increased microbiome diversity was associated with increasing severity of cervical neoplasm and CC.
Kwon et al45	CIN (n = 17) CC (n = 12) Control (n = 18)	Whole-genome sequencing	Alkaliphilus, Pseudothermotoga, Wolbachia, Lactobacillus, Staphylococcus, Candidatus Endolissoclinum	Diversity was not significantly associated with disease status. CC and CIN were each significantly enriched with bacteria unique to the other disease status.
Studies on the Gut (Fecal) Microbiome and Cervical Cancer
Wang et al50	ICC (n = 8) Control (n = 5)	V4 16S rRNA	Proteobacteria, Parabacteroides, Escherichia-Shigella, Roseburia	Increased α-diversity (NS) and differing β-diversity of gut microbiome in CC versus control. Seven genera differentiated significantly in relative abundance between CC and controls.
Sims et al51	ICC (n = 42) Control (n = 46)	V4 16S rRNA	Prevotella, Porphyromonas, Dialister	Increased α-diversity and differing β-diversity in CC versus control. CC patients exhibited significantly enriched Prevotella, Porphyromonas, and Dialister when compared to age, race, and BMI-matched controls.

CC: cervical cancer; HSIL: high-grade squamous intraepithelial lesion; ICC: invasive cervical cancer; LSIL: low-grade squamous intraepithelial lesion; SIL: squamous intraepithelial lesion.