Associations of Cervicovaginal Lactobacilli With High-Risk Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia, and Cancer: A Systematic Review and Meta-Analysis

Abstract Background Vaginal dysbiosis characterized by depleted lactobacilli is usually correlated with human papillomavirus (HPV) infection and cervical carcinogenesis, but the effect of the Lactobacillus genus and represented species on this process remains unclear. Methods PubMed, EMBASE, and CENTRAL databases were searched up to February 15, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model and Review Manager (version 5.3) for Mac. Results Eleven studies comprising 1230 cases were included. Lactobacillus spp. was associated with the decreased detection of high-risk subtype (hr)HPV infection (OR = 0.64, 95% CI = 0.48–0.87, I2 = 6%), cervical intraepithelial neoplasia (CIN) (OR = 0.53, 95% CI = 0.34–0.83, I2 = 0%), and cervical cancer (CC) (OR = 0.12, 95% CI = 0.04–0.36, I2 = 0%). At the level of Lactobacillus species, Lactobacillus crispatus, but not Lactobacillus iners, was correlated with the decreased detection of hrHPV infection (OR = 0.49, 95% CI = 0.31–0.79, I2 = 10%) and CIN (OR = 0.50, 95% CI = 0.29–0.88, I2 = 0%). Conclusions Cervicovaginal Lactobacillus spp. is associated with the decreased detection of hrHPV infection, CIN, and CC; L. crispatus may be the critical protective factor.

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The Correlation Between Bacterial Vaginosis, High-Risk Human Papillomavirus Infection, and Cervical Intraepithelial Neoplasia Progression

10.21203/rs.3.rs-998392/v1 ◽

2021 ◽

Author(s):

Xiaolin Xu ◽

Yichan Zhang ◽

Liqun Yu ◽

Xingxian Shi ◽

Min Min ◽

...

Keyword(s):

Risk Factors ◽

Human Papillomavirus ◽

High Risk ◽

Bacterial Vaginosis ◽

Cervical Intraepithelial Neoplasia ◽

Protective Factor ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Vaginal Microbiota ◽

Papillomavirus Infection

Abstract Persistent infection with high-risk human papillomavirus (HR-HPV) is an important reason for the progression of cervical intraepithelial neoplasia (CIN). Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with HPV, but the correlation between BV and HPV during CIN development is still elusive. In this study, we enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with or without BV and HPV co-infection and then calculated risk factors for CIN progression by logistic regression. We found that condom use (OR=3.480; 95% CI=1.069-11.325; P < .05) was a protective factor against CIN, whereas BV (OR=0.358; 95% CI=0.195-0.656; P < .05) and HR-HPV infection (OR= 0.016; 95% CI=0.004-0.072; P < .001) were risk factors for CIN. BV and HPV infection could trigger an increase in the diversity of vaginal microbiota and decrease Lactobacillus domination, which is conducive to CIN regression. The depletion of the carbohydrate metabolism pathway may induce Lactobacillus reduction. Treating BV in the clinical setting could block CIN development and L. iners may be a crucial species during this process.

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Correlation between Human Papillomavirus Codetection Profiles and Cervical Intraepithelial Neoplasia in Japanese Women

Microorganisms ◽

10.3390/microorganisms8121863 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1863

Author(s):

Kaori Okayama ◽

Hirokazu Kimura ◽

Koji Teruya ◽

Yasuyoshi Ishii ◽

Kiyotaka Fujita ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Hpv Genotypes ◽

High Risk Type ◽

Pcr Method ◽

Polymerase Chain ◽

High Risk Hpv

Human papillomavirus (HPV) infection is thought to be strongly associated with the precarcinomatous state cervical intraepithelial neoplasia (CIN) and cervical carcinoma. To accurately assess the correlation between HPV detection profiles and CIN, the uniplex E6/E7 polymerase chain reaction (PCR) method was used. We detected HPV (37 genotypes) in 267 CIN cases. The detection of a single high-risk HPV genotype occurred in 69.7% of CIN1 and worse than CIN1 (CIN1+) cases whereas other types were detected in 11.6% of cases. Codetection of high-risk HPV genotypes occurred in 4.9% of CIN1+ cases. The high-risk genotype HPV16 was the most frequently detected genotype in CIN1+ lesions; the genotype HPV34 (not a high-risk type) was detected in some CIN3 cases. Furthermore, HPV codetection may not be associated with CIN grades. These results suggest that various HPV genotypes are associated with CIN across all analyzed cases.

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A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia

Infectious Agents and Cancer ◽

10.1186/s13027-019-0243-8 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 6

Author(s):

Yuejuan Liang ◽

Mengjie Chen ◽

Lu Qin ◽

Bing Wan ◽

He Wang

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Large Scale ◽

Reproductive Tract ◽

Ureaplasma Urealyticum ◽

Meta Analysis ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Female Reproductive Tract ◽

Newcastle Ottawa Scale

Abstract Microecology is an emerging discipline in recent years. The female reproductive tract is an important microecological region, and its microecological environment can directly affect women’s cervical health. This meta-analysis aimed to analyze the effects of vaginal microecology on Human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). PubMed and Web of Science were systematically searched for eligible publications from January 2000 to December 2017. Articles were selected on the basis of specific inclusion and exclusion criteria. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) with a 95% confidence interval (95% CI) were calculated. Thirteen eligible studies were selected to evaluate the association of vaginal microecology with HPV infection and CIN. The factors related to HPV infection were bacterial vaginosis (BV) (OR 2.57, 95% CI 1.78–3.71, P<0.05), Candida albicans (VVC) (OR 0.63, 95% CI 0.49–0.82, P < 0.05), Chlamydia trachomatis (CT) (OR 3.16, 95% CI 2.55–3.90, P < 0.05), and Ureaplasma urealyticum (UU) (OR 1.35, 95% CI 1.20–1.51, P < 0.05). BV was also related to CIN (OR 1.56, 95% CI 1.21–2.00, P < 0.05). This meta-analysis of available literature suggested an intimate association of vaginal microecology and HPV infection with CIN. BV, CT and UU were associated to increased HPV infection, VVC was associated to decreased HPV infection, Lactobacillus is not associated to increased HPV infection, BV was associated to increased CIN development risk. Further large-scale studies are needed to confirm our findings.

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Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study

Vojnosanitetski pregled ◽

10.2298/vsp150205143g ◽

2017 ◽

Vol 74 (1) ◽

pp. 24-30 ◽

Cited By ~ 1

Author(s):

Mileta Golubovic ◽

Milena Lopicic ◽

Natasa Terzic ◽

Marija Djurovic ◽

Boban Mugosa ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Prospective Study ◽

Cervical Intraepithelial Neoplasia ◽

Pap Test ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Premalignant Lesions ◽

Cervical Lesions ◽

Female Patients

Background/Aim. In patients with premalignant cervical lesions, human papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap) test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. Methods. This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR) of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. Results. In the group of 80 (3.1%; n = 80/2,578) of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70%) of them had cervicitis, and 1/3 or 24 (30%) had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions. Conclusion. Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular) often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure.

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Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-020-05787-w ◽

2020 ◽

Vol 302 (6) ◽

pp. 1329-1337

Author(s):

Junya Zhang ◽

Keyan Cheng ◽

Zhilian Wang

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Infection Rate ◽

Meta Analysis ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Screening Tests ◽

Cochrane Library ◽

Hpv Vaccines ◽

Hpv Genotypes

Abstract Background and aim Data on type-specific human papillomavirus (HPV) are needed to investigate HPV-based screening tests and HPV vaccines. However, Chinese relevant data are insufficient. Therefore, this meta-analysis aimed to summarize and demonstrate the prevalence and distribution of HPV genotypes in cervical intraepithelial neoplasia (CIN) and compensate for the shortage of HPV vaccines in China. Methods The Medline, Embase, and the Cochrane Library databases, as well as references cited in the selected studies, were systematically searched for studies investigating the prevalence and distribution of HPV genotypes between January 2000 and April 2019 in China. Results A total of 8 studies were identified, which comprised 2950 patients with CIN1 and 5393 with CIN2/3. The overall HPV infection rate was 84.37%. The HPV infection rate was significantly higher in the CIN2/3 group (87.00%) than in the CIN1 group (79.56%) (χ2 = 80.095, P < 0.001). The most common HPV types in CIN1 in order of decreasing prevalence were as follows: HPV52 (20.31%), HPV16 (16.81%), HPV58 (14.44%), HPV18 (6.44%), and HPV53 (5.76%). However, in the CIN2/3 group, HPV16 (45.69%) was the predominant type, followed by HPV58 (15.50%), HPV52 (11.74%), HPV33 (9.35%), and HPV31 (4.34%). Conclusions This study suggested that HPV16, HPV52, and HPV58 were the top three types of CIN in China. The findings might provide a reference for future HPV-based cervical cancer screening tests, treatment of HPV infection, and application of HPV vaccines in China.

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Cervicovaginal Microbiome after Cervical Intraepithelial Neoplasia Treatment. A Protocol for Systematic Review and Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18179050 ◽

2021 ◽

Vol 18 (17) ◽

pp. 9050

Author(s):

Marta Janicka-Kośnik ◽

Beata Sarecka-Hujar ◽

Grzegorz Jakiel ◽

Aneta Słabuszewska-Jóźwiak

Keyword(s):

Systematic Review ◽

Cervical Intraepithelial Neoplasia ◽

Meta Analysis ◽

Chemical Properties ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Adverse Outcomes ◽

Lactobacillus Species ◽

Treatment Change ◽

Randomized Controlled Studies

(1) Background: The microbiome consists of microorganisms from various kingdoms with numerous physical and chemical properties Lactobacillus species constitute the highest percentage of healthy cervical and vaginal microbiota. Dysbiosis may cause adverse outcomes, e.g., bacterial vaginosis, pelvic inflammatory disease and pregnancy complications. The cervicovaginal microbiome might contribute to the development of a persistent HPV infection—the main risk factor of cervical cancer—and influence progression to malignancy The aim is to perform a systematic review of current literature and a meta-analysis regarding microbiome changes after cervical intraepithelial neoplasia treatment. (2) Methods: We will search PubMed, Scopus, Google Scholar and Embase Database and trace citations in the reference sections. Randomized and non-randomized controlled studies, case–control and cohort studies published between January 2000 and May 2021 will be included in the study protocol. The following keywords will be used: ‘microbiome’, ‘vaginal microbiome’, ‘cervical microbiome’, ‘cervical neoplasia treatment’, ’conization’, ‘electroconization’, and ‘electrosurgical treatment’. Statistical analyses will be performed using RevMan 5.4. (3) Results: The results will be published as a peer-reviewed article. (4) Conclusions: The study will show which forms of intraepithelial neoplasia treatment change the cervicovaginal microbiome. Finding the best form of treatment by studying the cervicovaginal microbiome after various forms of treatment is essential. Patients would benefit not only from the treatment of the initial disease but also the management of dysbiosis, which might underlie other pathologies.

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