Research of the Potential Vaginal Microbiome Biomarkers for High-Grade Squamous Intraepithelial Lesion

Vaginal microbiome may have a role in HPV infection and cervical neoplasm. To explore potential vaginal microbiome biomarkers for high-grade squamous intraepithelial lesion (HSIL), and to find the best scheme to facilitate the current cervical cancer screening strategy. This study enrolled 272 women, including 83 confirmed with HSIL, 86 with HPV infection but without cervical neoplasm, and 103 without HPV infection as controls. Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. The relative increasing abundance of Stenotrophomonas, Streptococcus, and Pseudomonas, and a concomitant paucity of Dialister, unidentified Prevotellaceae, Faecalibacterium, Bifidobacterium, and Bacteroides, were related with HSIL, which can be used to predict the development of HISL in high-risk HPV infected patients. The relative abundance of Stenotrophomonas being over 0.0090387%, or Faecalibacterium being under 0.01420015%, or Bifidobacterium being under 0.0116183% maybe a good predictor for HSIL for those infected with HPV 16 and/or 18. The relative abundance of Stenotrophomonas being over 0.01549105%, or Streptococcus being over 0.48409585%, or Bacteroides being under 0.0296912% maybe a good predictor for HSIL for those infected with the 12 other high-risk types of HPV with concurrent abnormal TCT results. This study revealed that potential vaginal microbiome biomarkers may relate to HSIL, and can facilitate the cervical cancer screening.

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Characteristics of high-risk human papillomavirus infection in women with abnormal cervical cytology: a population-based study in Shanxi Province, China

10.21203/rs.2.15784/v1 ◽

2019 ◽

Author(s):

Li Song ◽

Yuanjing Lyu ◽

Ling Ding ◽

Xiaoxue Li ◽

Wen Gao ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Risk ◽

Hpv Infection ◽

Cervical Cytology ◽

Shanxi Province ◽

Low Grade ◽

Squamous Intraepithelial Lesion ◽

Abnormal Cervical Cytology ◽

Intraepithelial Lesion

Abstract Background: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer and it’s characteristics vary greatly in different population. Women with abnormal cervical cytology could increase the risk of cervical cancer, however, HR-HPV infection characteristics in women with abnormal cervical cytology remains unclear. Methods: This study was based on baseline survey of the CIN Cohort established in Shanxi Province, China. A total number of 2300 women with cervical abnormalities were enrolled in this study. All participants gave informed consent and agreed to HPV and thinprepcytologic test (TCT). Each individual completed a questionnaire about characteristics related to HPV infection. Results: The overall prevalence of HR-HPV in 2300 women was 32.0%, and the proportion of single and multiple HR-HPV infections were 70.2% and 29.8% in HR-HPV infection women, respectively. The top five HR-HPV genotypes were ranked as HPV16, HPV58, HPV52, HPV53 and HPV51. The prevalence of HR-HPV in atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion and above(HSIL+) were 30.8%, 36.5% and 54.9%, respectively, showing an increasing trend with the severity of cervical cytology ( χ 2 trend =13.952; p <0.001). The women aged 35~45 years, with lower education level, less frequency of bathing, multiple gravidity, multiple parity, history of gynecological diseases and premenopausal women were prone to HR-HPV infection. Conclusions: We defined the characteristics related to HR-HPV infection in abnormal cervical cytology women, and provided an insight for the development and deeply research of HPV vaccine.

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Case Report: Noninvasive Clinical Intervention of REBACIN® on Histologic Regression of High Grade Cervical Intraepithelial Neoplasia

Frontiers in Medicine ◽

10.3389/fmed.2021.627355 ◽

2021 ◽

Vol 8 ◽

Author(s):

Fan Wang ◽

Rong Liu ◽

Yan Ma ◽

Dai-Fei Wu ◽

Liu-Hong Deng ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Clinical Intervention ◽

Intraepithelial Neoplasia ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Non Invasive ◽

Future Fertility ◽

Intraepithelial Lesion ◽

High Risk Hpv

High-risk human papillomavirus (hrHPV) persistent infection is the major cause of cervical cancer. Clinical intervention of hrHPV-associated high-grade squamous intraepithelial lesion (HSIL) is critical to prevent cervical cancer, and current treatment is surgery (an invasive therapy). However, some patients refuse to do so for an afraid of potential adverse effects on future fertility or other concerns which creates a critical need for development of non-invasive therapeutic strategies. Here, we report for the first time the cases of non-invasive intervention with REBACIN®, a proprietary antiviral biologics, in clinical treatment of HSIL. From 12,958 visiting patients assessed for eligibility, 18 HSIL-patients with cervical intraepithelial neoplasia-grade 2, positive of both diffused overexpression of p16 and high-risk HPV were enrolled in this non-invasive clinical intervention mainly due to concerns of future fertility. REBACIN® was administered intravaginally every other day for 3 months (one-course) except during menstrual period, and were followed up for 6-36 months for the examination of high-risk HPV DNA, cervical cytology, and histopathology. After one to three course treatments, most cases (16/18) displayed both the regression from HSIL (CIN2) to normal cervical cytology and clearance of high-risk HPV infection. Further studies demonstrated REBACIN® significantly suppressed HPV16 E7 oncoprotein expression in a human cervical cancer cell line, which is consistent with previous finding that REBACIN® inhibits the growth of tumors induced by expression of E6/E7 oncogenes of either HPV16 or HPV18. This report indicates REBACIN® as a novel effective non-invasive clinical intervention for HSIL-patients as well for high-risk HPV persistent infection, providing a new clinical option for the non-invasive treatment of hrHPV-associated high-grade squamous intraepithelial lesion, which is worthy of further research on clinical validation and application.

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Atypical Squamous Cells, Cannot Exclude High-Grade Squamous Intraepithelial Lesion: Concordance, High-Risk Human Papillomavirus status, and Positive Predictive Value

Journal of the American Society of Cytopathology ◽

10.1016/j.jasc.2015.09.060 ◽

2015 ◽

Vol 4 (6) ◽

pp. S25-S26

Author(s):

Mansooreh Eghtesadghalati ◽

Ruth Dietrich ◽

Erin Tank ◽

Michelle Kanter ◽

John Groth ◽

...

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Positive Predictive Value ◽

Predictive Value ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Squamous Cells ◽

Intraepithelial Lesion

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Impact of human papillomavirus coinfections on the risk of high-grade squamous intraepithelial lesion and cervical cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2014.06.018 ◽

2014 ◽

Vol 134 (3) ◽

pp. 534-539 ◽

Cited By ~ 22

Author(s):

Adela Carrillo-García ◽

Sergio Ponce-de-León-Rosales ◽

David Cantú-de-León ◽

Verónica Fragoso-Ontiveros ◽

Imelda Martínez-Ramírez ◽

...

Keyword(s):

Cervical Cancer ◽

Human Papillomavirus ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Intraepithelial Lesion

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Risk factors of persistent HPV infection after treatment for high-grade squamous intraepithelial lesion

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-018-4936-9 ◽

2018 ◽

Vol 299 (1) ◽

pp. 223-227 ◽

Cited By ~ 1

Author(s):

Kyeong A So ◽

In Ho Lee ◽

Tae Jin Kim ◽

Ki Heon Lee

Keyword(s):

Risk Factors ◽

Hpv Infection ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Intraepithelial Lesion

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High-risk HPV genotypes and cervical lesions association in postmenopausal women

European Journal of Public Health ◽

10.1093/eurpub/ckab120.044 ◽

2021 ◽

Vol 31 (Supplement_2) ◽

Author(s):

Ana Rita Fernandes Miranda da Costa ◽

Cláudia Sousa ◽

Erica Isidoro ◽

Regina Silva ◽

Cristiana Mourato

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Postmenopausal Women ◽

Age Groups ◽

Low Grade ◽

High Grade ◽

Cervical Lesions ◽

Intraepithelial Lesion ◽

The Bethesda System ◽

High Risk Hpv

Abstract Background Persistent infection by high-risk Human Papillomavirus (hrHPV) are the major cause of cervical cancer. Studies report disparities in the incidence of infection and the various genotypes of this virus in different age groups, suggesting a higher frequency of hrHPV in young women and low-risk subtypes being predominant in older women. This study aimed to investigate the incidence and distribution of hrHPV genotypes in postmenopausal women as well as the correlation with the cytological findings. Methods 16 859 women, aged 50–64 years, performed cervical cancer screening test in Friuri Venezia Giulia region, Italy. The infection was evaluated by the Polymerase Chain Reaction methodology and the positive samples were evaluated by Liquid Based Cytology according to the Bethesda System from 2014. A statistical analysis was performed to study the molecular and cytological data of this population. Results hrHPV infection were found in 5.8% of the women and 78.3% of these were caused by hrHPV other than HPV16 and HPV18 (). Also, 65.7% of the positive samples were negative for intraepithelial lesion or malignancy while low grade squamous intraepithelial lesion was the most frequent (22.4%). There was an increase in the number of high-grade intraepithelial lesions in the presence of HPV16 compared to that recorded when this genotype was absent (20.8% vs. 8.5%). No cervical cancers were detected. Conclusions Infection with hrHPV is uncommon in postmenopausal women and it is mostly caused by subtypes less associated with the development of cervical cancer. Yet, HPV16 infection triggers the development of high-grade lesions.

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Significance of survivin immunoreactivity and morphometric analysis of HPV-induced cervical dysplasia

Archives of Biological Sciences ◽

10.2298/abs1401429v ◽

2014 ◽

Vol 66 (1) ◽

pp. 429-436

Author(s):

Biserka Vukomanovic-Djurdjevic ◽

Gordana Basta-Jovanovic ◽

N. Baletic ◽

Milica Berisavac ◽

D. Nenadic ◽

...

Keyword(s):

High Risk ◽

Human Papilloma Virus ◽

Morphometric Analysis ◽

Cervical Dysplasia ◽

Epithelial Dysplasia ◽

Control Group ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Papilloma Virus ◽

Intraepithelial Lesion

Genomic integration of high-risk human papilloma virus in the nucleus of cervical epithelial mucosal cells leads to epithelial dysplasia. The aim of this study was to determine the relevance of correlation between epithelial survivin expression and the degree of human papilloma virus (HPV)-induced cervical epithelial dysplasia, and to establish the significance of morphometric analysis of the nuclear area in the assessment of the degree of cervical dysplasia. This retrospective study included 99 women with primary, previously untreated lesions, and colposcopic findings indicating dysplasia, in whom a cytological test by Papanicolaou method was interpreted according to the Bethesda criteria as lowgrade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and atypical squamous cells of undetermined significance (ASCUS). We performed human papilloma virus (HPV) typing by PCR for evidence of viruse types 16, 18, 31, 33. After biopsy of the cervical mucosa, we performed hematoxylin-eosin (H-E) and Periodic Acid Schiff (PAS) staining, and immunohistochemical and morphometric analysis of tissue samples. The control group consisted of 12 women without dysplasia and without a verified infection of cervical high-risk HPV. A high statistical correlation between the degree of dysplasia and expression of survivin was found in patients with different types of cervical dysplasia (p = 0.003). We observed a high statistical difference between the area of nuclei at different degrees of cervical dysplasias (p = 0.000). The high-grade cervical dysplasia had a more than 2-fold higher level of ranking in comparison to low-grade dysplasia, and a more than 10-fold higher ranking than the control group without cervical dysplasia.

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