Does the vaginal microbiota play a role in the development of cervical cancer?

Kyrgiou, Maria; Mitra, Anita; Moscicki, Anna‐Barbara

doi:10.1016/j.trsl.2016.07.004

Cited by 200 publications

(201 citation statements)

References 122 publications

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“…Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer 2. Additional factors correlated with persistent HPV infection include immunodeficiency caused by HIV, smoking, oral contraceptives and, more recently reported, vaginal dysbiosis 3.…”

Section: Introductionmentioning

confidence: 99%

Correlation between the diversity of vaginal microbiota and the risk of high-risk human papillomavirus infection

Chao

Sun

Wang

et al. 2019

Int J Gynecol Cancer

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ObjectivesSince other genital infections enhance HIV susceptibility by inducing inflammation and evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of high-risk human papillomavirus (HPV) infections, we investigated the relationship between the composition of the vaginal microbiota and the risk of high-risk HPV infection.MethodsThe study included 151 healthy women (65 HPV-positive and 86 HPV-negative) aged 20–65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500.ResultsOf the 30 most abundant bacteria at the genus level, we found only six bacteria with a statistical difference between HPV-positive and HPV-negative women: Bacteroides, Acinetobacter, Faecalibacterium, Streptococcus, Finegoldia, and Moryella. Lactobacillus was the predominant genus and was detected in all women, but there was no significant difference between the two groups for L. iners, L. jensenii, and L. gasseri. Furthermore, we found 26 types of bacteria with a statistical difference at the species level between the two groups. Anaerobic bacteria such as Bacteroides plebeius, Acinetobacter lwoffii, and Prevotella buccae were found significantly more frequently in HPV-positive women, which is the most important finding of our study.ConclusionOur findings suggest a possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high-risk HPV infection. The exact molecular mechanism of the vaginal microbiota in the course of high-risk HPV infection and cervical neoplasia should be further explored. Future research should include intervention in the composition of the vaginal microbiota to reverse the course of high-risk HPV infection and the natural history of cervical neoplasia.

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Section: Introductionmentioning

confidence: 99%

Correlation between the diversity of vaginal microbiota and the risk of high-risk human papillomavirus infection

Chao

Sun

Wang

et al. 2019

Int J Gynecol Cancer

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“…However, various infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonas vaginitis (TV), and reduction in estrogen may cause abnormalities of the vaginal microenvironment, such as decreased lactobacilli, elevated vaginal pH, etc . The abnormal vaginal microenvironment, which damages the vaginal mucosa and cervical epithelium, may enhance the continuous HPV infection, reduce the clearance rate of HPV, and ultimately increased the risk of CIN . Our results also indicated that the risk of CIN2+, CIN3+ was significantly increased when the vaginal pH > 4.5 (middle and high pH).…”

Section: Discussionmentioning

confidence: 60%

A population‐based study of age‐related associations between vaginal pH and the development of cervical intraepithelial neoplasia

Teng

Hao

2020

Cancer Medicine

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The association between vaginal pH and the risk of cervical intraepithelial neoplasia (CIN) is unclear. We evaluated the dose‐response relationship between vaginal pH and CIN risk, as well as the combined influence of vaginal pH and high‐risk human papillomavirus (hrHPV) on the risk of CIN and the mediation effects of hrHPV infection on vaginal pH level and the development of CIN. We investigated 2304 women in Shanxi, China. The dose‐response relationship between vaginal pH and CIN risk was assessed using categoric and spline analyses. We established interaction and mediation models to determine the correlation between pH and hrHPV in the development of CIN. After adjusting covariates, a positive association was observed between hrHPV infection and the development of CIN [OR (95% CI) = 4.75 (3.52‐6.40) for CIN2+; OR (95% CI) = 7.30 (4.10‐13.00) for CIN3+], while a negative correlation was showed between vaginal pH level and CIN3+ [OR (95% CI) = 1.04 (0.59‐1.84); high vs low: OR (95% CI) = 0.32 (0.15‐0.69), P = .002]. The highest risk of CIN (5.24 of CIN2+ and 5.80 of CIN3+) were observed when hrHPV infection was combined with middle vaginal pH (4.6‐5.0). A significant mediation effect of hrHPV infection was observed in the association between vaginal pH level with CIN2+ (P = .002) and CIN3+ (P = .004). In conclusion, abnormal vaginal pH significantly induced the risk of high‐stage CIN in Chinese women infected with hrHPV. Therefore, maintaining normal vaginal pH levels may reduce the risk of CIN.

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“…HPV, particularly types 16, is transmitted sexually and when in contact with the transformation zone of the cervix is known to contribute to invasive cervical carcinoma. But recurrent or persistent infection with the oncogenic HPV is necessary but not sufficient for the development of CC (25,26), there may be other carcinogenic factors or some factors that work together with HPV for carcinogenesis. Our study was designed to comprehensively evaluate the effects of folate on the progression from the NC, low-grade cervical intraepithelial neoplasia, high-grade cervical intraepithelial neoplasia to CC at the angle of groups, meanwhile, the effect of folate on cervical carcinogenesis was demonstrated by folate intervention at the angle of vitro.…”

Section: Discussionmentioning

confidence: 99%

Folate deficiency and aberrant DNA methylation and expression of FHIT gene were associated with cervical pathogenesis

Ding

Nan

et al. 2017

Oncol Lett

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Abstract. Aberrant DNA methylation is a recognized feature in various types of human cancer, and folate has a vital role in the epigenetics of mammalian cells by supplying methyl groups for DNA methylation reactions. Fragile histidine triad (FHIT) is a tumor suppressor gene that is frequently silenced in cervical cancer (CC) and preneoplastic lesions. Promoter hypermethylation was previously observed in CC, and its epigenetic silencing has been observed at mRNA or protein levels. Changes in folate intake to modulate DNA methylation may be a mechanistic link to cancer, but this remains to be elucidated. The aim of the present study was to evaluate the influences of folate on FHIT gene methylation and expression in the progression of cervical cancerization. In the present study, red blood cell (RBC) folate levels, FHIT gene methylation status, and mRNA and protein expression levels were detected in 254 women, including normal cervix (NC, n=80), cervical intraepithelial neoplasm grade 1 (CIN1, n=55; CIN2/3, n=55) and cervical squamous cell carcinoma (SCC, n=64) samples. The methylation status of FHIT gene and its mRNA and protein expression levels were measured in CaSki (HPV16 positive) and C33A (HPV16 negative) CC cells treated with different concentrations of folate. The results indicated that FHIT gene methylation rate increased with the severity of cervix lesions, however, RBC folate levels, FHIT mRNA and protein expression levels were reduced. The proliferation inhibition rate, apoptosis rate, and FHIT protein and mRNA expression levels increased along with rising concentrations of folate, whereas the degree of FHIT gene methylation gradually weakened in CaSki or C33A cell lines. The present findings indicated that folate deficiency, FHIT gene promoter hypermethylation and reduced expression were significantly associated with cervical carcinogenesis. The results indicated that folate was able to enhance apoptosis and inhibit the cervical cell proliferation while regulating FHIT gene methylation and expression. Adequate intake of folate to maintain normal DNA methylation status is an effective way for cervical lesions prevention, and demethylation treatment may offer a new strategy for therapy of CC.

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Does the vaginal microbiota play a role in the development of cervical cancer?

Cited by 200 publications

References 122 publications

Correlation between the diversity of vaginal microbiota and the risk of high-risk human papillomavirus infection

Correlation between the diversity of vaginal microbiota and the risk of high-risk human papillomavirus infection

A population‐based study of age‐related associations between vaginal pH and the development of cervical intraepithelial neoplasia

Folate deficiency and aberrant DNA methylation and expression of FHIT gene were associated with cervical pathogenesis

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