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Table 1 Characteristics of studies exploring the association of HPV infection and cervical preinvasive and invasive cervical disease to the vaginal microbiome using next-generation sequence techniques

From: The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?

Study Summary of findings Study characteristics
Lee et al. [52] Summary of findings
− HPV positivity = higher diversity and lower proportion of Lactobacillus spp. compared to HPV-negative women (19 HPV-positive women vs 26 HPV-negative women)
Sneathia spp. = microbiological marker of HPV infection (19 HPV-positive women vs 26 HPV-negative women)
L. iners reduced in HPV-positive vs negative monozygotic (MZ) HPV-discordant twins (9 twin pairs, 18 women) (P = 0.03)
Participants: 912 women who participated in the Healthy Twin Study, a part of the Korean Genome Epidemiology Study; 68 female twins, their mothers and sisters including 9 HPV infection-discordant MZ twin pairs without CIN and 45 premenopausal women with or without HPV infection
Sexual history meta-data: not reported
VMB sampling: clinician-collected high vaginal swabs
HPV testing technique: MY09/MY11 and GP5+/GP6+, PCR amplicons of 450 and 150 bp and HPV typing (high vs low risk)
NGS technique: 16 s rRNA gene regions: V2 and V3, primers barcoded: 8F and 534R, platform: Roche 454 Life Sciences FLX Titanium
Brotman et al. [19] − CST was significantly associated with remission of HPV (P = 0.008)
− CST IV-A higher transition to HPV positivity compared to CST I (aTRR: 1.86, 95 %CI 0.52–6.74)
− Fastest remission of HPV infection - CST II (aTRR: 4.43, 95 % CI 1.11–17.7 when compared to CST I)
− Slowest remission of HPV infection = CST IV-B (aTRR: 0.33, 95 % CI 0.12–1.19 when compared to CST I)
Participants: premenopausal women taking bi-weekly samples over 16-week period as part of a douching cessation study; 5 consistently HPV negative, 2 positive for 1 HPV subtype, 25 positive for 2 or more HPV subtypes
Sexual history meta-data: monogamous relationship, number of lifetime sexual partners and daily diary including frequency and type of intercourse and type of contraception used
VMB sampling: mid-vaginal swabs, self-sampling
HPV testing technique: Roche Linear Array HPV Genotyping Test (37 high- and low-risk subtypes)
NGS technique: 16 s rRNA gene regions: V1–V2, primers barcoded: 27F and 338R, platform: Roche 454 Life Sciences FLX Titanium machine
Mitra et al. [54] − CST IV associated with increasing disease severity (normal = 10 %; LSIL = 21 %; HSIL = 27 %; ICC = 40 %)
− CST I negatively associated with increasing disease severity (normal = 50 %; LSIL = 42 %; HSIL = 40 %; ICC = 20 %) - higher levels of S. sanguinegens (P < 0.01), A. tetradius (P < 0.05), P. anaerobius (P < 0.05) associated with HSIL vs LSIL
− Lower levels L. jensenii (P < 0.01) associated with HSIL vs LSIL
Participants: 169 premenopausal women attending colposcopy clinic; 20 normal, 52 LSIL, 92 HSIL, 5 ICC
Sexual history meta-data: history of intercourse in 48 h prior to sampling, type of contraception used
VMB sampling: clinician-collected, high vaginal swab
HPV testing technique: Abbott RealTime HR HPV assay (Abbott M2000 platform)
NGS technique: 16 s rRNA gene regions: V1-V2, primers barcoded: 27F and 338R, platform: Ilumina MiSeq
Oh et al. [56] Higher risk of CIN for the higher vs the lower tertile of
A. vaginae, G. vaginalis, L. iners predominance with a minority of L. crispatus: OR 5.80, 95 % CI 1.73–19.4 - A. vaginae: OR 6.63, 95 % CI 1.61–27.2
− Risky microbial pattern in presence of oncogenic HPV: OR 34.1, 95 % CI 4.95–284.5
Participants: 120 premenopausal women attending gynaecological oncology clinics; 70 CIN cases: CIN1 (n = 55), CIN2 or CIN3 (n = 15), controls: normal cytology (n = 25), ASCUS (n = 25)
Sexual history meta-data: not reported, use of oral contraception recorded
VMB sampling: clinician-collected digene cervical sampler brush
HPV testing technique: hybrid capture II DNA Test (Qiagen, Gaithersburg, MD, USA)
NGS technique: 16 s rRNA gene regions: V1–V3, primers barcoded: not stated, platform: Roche/454 Genome Sequencer Junior
Piyathilake et al. [57] Summary of findings
L. iners and unclassified Lactobacillus spp. associated with higher CIN2+ rates compared to diverse taxa unclassified Lactobacillus spp, L. iners, Bifidobacteriaceae, Clostridiales, Allobaculum (OR = 3.48, 95 % CI 1.27–9.55)
− Lactobacillaceae, Lactobacillus, L. reuteri and several sub-genus level Lactobacillus OTUs higher in women with CIN2+ vs CIN1
− DNA oxidative damage does not correlate with VM structure
Participants: 430 hrHPV positive women aged 19–50 years attending colposcopy clinics; 340 cases: CIN2 (n = 208), CIN3 (n = 132), 90 non-cases: all CIN1
Sexual history meta-data: not reported, use of oral contraception recorded
VMB sampling: clinician-collected high vaginal swabs (Merocel ophthalmic sponges)
HPV testing technique: Roche Diagnostics Linear Array
NGS technique: 16 s rRNA gene region: V4, primers barcoded: not stated, platform: Illumina MiSeq
Audirac-Chalifour et al. [55] Summary of findings
− VMB diversity significantly higher in CIN and ICC compared to normal, HPV-negative women (P = 0.006, P = 0.036, respectively)
L. crispatus and L. iners predominate in normal women
Sneathia spp. predominate in women with CIN
Fusobacterium spp. in women with ICC
− Highest mean levels of IL-4 and TGF-β1 mRNA in Fusobacterium spp. VMBs
Participants: 32 women aged 22–61 years, selected from a biobank, recruited from the gynaecological service at a National Cancer Institute; 20 normal (10 HPV negative, 10 HPV positive), 4 CIN (all HPV positive), 8 ICC (all HPV positive)
Sexual history meta-data: age at first intercourse, number of lifetime sexual partners, no sexual activity ‘in previous days of the sampling’ (number of days not stated)
VMB sampling: cervical scraping swabs from normal women and fresh cell biopsies from women with CIN and ICC
HPV testing technique: Seegene Anyplex II HPV HR Detection assay
NGS technique: 16 s rRNA gene regions: V3–V4, primers barcoded 347F and 803R, platform: Roche/454 Genome Sequencer Titanium system
  1. aTRR adjusted transition rate ratio, A. vaginae Atopobium vaginae, CI confidence interval, CIN cervical intraepithelial neoplasia, HPV human papillomavirus, hrHPV high-risk HPV, HSIL high-grade squamous intraepithelial lesion, ICC invasive cervical cancer, L Lactobacillus, LSIL low-grade squamous intraepithelial lesion; MZ monozygotic twins, NGS next-generation sequencing, OR odds ratio, OTUs operational taxonomic units, SIL squamous intraepithelial lesion, VM vaginal microbiome