Development Of Cervical Intraepithelial Neoplasia Research Articles

Cervical microbiota dysbiosis associated with high-risk Human Papillomavirus infection.

High-risk Human Papillomavirus (HR-HPV) genotypes, specifically HPV16 and HPV18, pose a significant risk for the development of cervical intraepithelial neoplasia and cervical cancer. In the multifaceted cervical microenvironment, consisting of immune cells and diverse microbiota, Lactobacillus emerges as a pivotal factor, wielding significant influence in both stabilizing and disrupting the microbiome of the reproductive tract. To analyze the distinction between the cervical microbiota and Lactobacillus-dominant/non-dominant status of HR-HPV and non-infected healthy women, sixty-nine cervical swab samples were analyzed, included 44 with HR-HPV infection and healthy controls. All samples were recruited from Human Papillomavirus-based cervical cancer screening program and subjected to 16s rRNA sequencing analysis. Alpha and beta diversity analyses reveal no significant differences in the cervical microbiota of HR-HPV-infected women, including 16 and 18 HPV genotypes, and those with squamous intraepithelial lesion (SIL), compared to a control group. In this study we identified significantly lower abundance of Lactobacillus mucosae in women with HR-HPV infection compared to the control group. Furthermore, changes in bacterial diversity were noted in Lactobacillus non-dominant (LND) samples compared to Lactobacillus-dominant (LD) in both HR-HPV-infected and control groups. LND samples in HR-HPV-infected women exhibited a cervical dysbiotic state, characterized by Lactobacillus deficiency. In turn, the LD HR-HPV group showed an overrepresentation of Lactobacillus helveticus. In summary, our study highlighted the distinctive roles of L. mucosae and L. helveticus in HR-HPV infections, signaling a need for further research to demonstrate potential clinical implications of cervical microbiota dysbiosis.

Laurencia johnstonii extract reverses early lesions in the K14E7HPV16 murine cervical carcinogenesis model.

Persistent infection with high-risk human papillomavirus (HR-HPV) is a well-established risk factor to the development of cervical intraepithelial neoplasia (CIN), a condition that can progress to cervical cancer (CC) a major health problem worldwide. Recently, there has been growing interest in exploring alternative therapies utilizing natural products, among which is the algae species Laurencia johnstonii Setchell & Gardner, 1924 (L. johnstonii), proposed for the management of precancerous lesions. The aim of this work was to determine the effect of an organic extract from L. johnstonii (ELj) in early cervical lesions (CIN 1). These CIN 1 lesions were generated in a murine model expressing the HR-HPV16 E7 oncoprotein (K14E7HPV transgenic mice) with a single exogenous hormonal stimulus using 17β-estradiol. The histopathological studies, the determination of cell proliferation and of the apoptotic levels in cervical tissue, showed that, seven doses of ELj (30 mg/kg weight per day diluted in a DMSO-saline solution [1:7]) lead to recovery the architecture of cervical epithelium. Accordingly, in the transgenic mice it was observed a statistically significant decrease of the PCNA expression levels, a marker of cell proliferation, and a statistically significant increase in the apoptosis levels using Caspase 3 as a marker. In addition, we determined the expression levels of the tumor suppressor miR-218 and the oncomiRNA miR-21. Interestingly, our results may suggest that ELj treatment tended to restore the normal expression of both miRNAs as compared with controls being more evident in the non-transgenic induced mice. Differences of p < 0.05 were considered statistically significant through the whole study. Based on these results, we propose that the use of ELj could be an alternative for the treatment of cervical early lesions.

Cervicovaginal microbiota long-term dynamics and prediction of different outcomes in persistent human papillomavirus infection.

Persistent human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer, posing serious threats to the health of women. Although the cervicovaginal microbiota is strongly associated with CIN, the dynamics of the microbiota during CIN development are unknown. In this retrospective cohort study, we analyzed 3-year longitudinal data from 72 patients diagnosed with a persistent HPV infection almost all caused by high-risk HPV types. Patients were categorized into groups with HPV persistent infection (n = 37), progression to CIN (n = 16), and CIN regression (n = 19) based on infection outcome during the follow-up period. Furthermore, 16S rRNA gene sequencing was performed on consecutively collected cervical samples to explore the composition and dynamics of the cervicovaginal microbiota during the development and regression of CIN. Our results showed that the composition of the cervicovaginal microbiota varied among women with different HPV infection outcomes and remained relatively stable during the follow-up period. Notably, the serial follow-up data showed that these microbial alterations were present for at least 1-2 years and occurred before pathologic changes. In addition, microbial markers that were highly discriminatory for CIN progression or regression were identified. This study provides evidence for a temporal relationship between changes in the cervicovaginal microbiota and the development of CIN, and our findings provide support for future microbial intervention strategies for CIN.

Immediate histologic correlation in patients with different HPV genotypes and ages: a single center analysis in China

BackgroundHuman papillomavirus (HPV) has been confirmed as a major causative factor for malignant transformation of cervical epithelial cells and for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We carried out this study to investigate the association of different HPV genotypes and ages with immediate histological cervical lesions in opportunistic screening patients in a single center.MethodsA total of 1,661 samples with biopsy-confirmed histologic findings were collected from the gynecological clinic of our hospital between October 2017 and May 2020 for analysis. The distribution of single-type HPV genotypes in CIN of different severities and the age-dependent prevalence for single-type HPV infection were analyzed.ResultsIn both CIN2 and CIN3 group, HPV16, 58, 52, 33 and 31/18 were detected as top 5 high-risk human papillomavirus (hrHPV) types, which accounts for 89.25% and 88.54% of single HPV infection incidence respectively. Besides, not a single case of HPV45 was found in CIN2 and CIN3. HPV16 was the dominant genotype in both CIN2 and CIN3, accounted for 46.24% and 55.21%, respectively. The prevalence of HPV16 was the most frequent in all the age groups, except ≥ 65 years group in CIN3, and almost one in three HPV16-positive patients were diagnosed with high grade CIN. The peak of the incidence of CIN3 was observed at 25 ~ 34 years (33.68%), followed by 35 ~ 44 years (31.58%).ConclusionHigh grade CIN peak at 25 ~ 44 years, women of this age are recommended for normative screening if conditions permit. HPV16-positive patients should be given high priority in opportunistic screening, while the single-center data suggesting a low risk of CIN2/3 in HPV45-positive patients. For women ≥ 65 years old, patients infected with other HPV types should be also taken seriously. In general, HPV16, 58, 52, 33, 31 and 18 were the most common genotypes in CIN2/3, and a vaccine including these predominant genotypes might be of great significance for cervical cancer prevention in China.

The prevalence of HPV among 164,137 women in China exhibited some unique epidemiological characteristics

ObjectiveThe persistence of HPV infection is a significant etiological factor in the development of cervical cancer. The present study investigated the prevalence and genotype distribution of human papillomavirus (HPV) in a cohort of 164,137 unvaccinated women from Wenzhou, aiming to provide guidance for clinics in the cervical cancer screening and HPV vaccination strategies.MethodsThe present retrospective study included a total of 164,137 women, comprising 118,484 outpatients and 45,653 healthy female subjects recruited from 2015 to 2020. Cervical exfoliated cells were collected from these participants for subsequent DNA extraction. The extracted DNA samples were underwent analysis using a fluorescence in situ hybridization method, encompassing the detection of 27 HPV genotypes.ResultsThe overall prevalence of HPV was 17.35%; this corresponded to a prevalence of 19.10% in the outpatient group and 12.82% in the healthy female group. Among the outpatient group, the five most prevalent HPV genotypes were identified as HPV 52, 58, 16, 53, and 61. In the healthy female group, the five most common HPV genotypes were found to be HPV 52, 53, 58, 61, and 81. Additionally, it was estimated that the highest rate of HPV infection occurred among individuals aged between 10 and 19 years old (44.65%) and those aged between 60 and 69 years old (27.35%).ConclusionsThe prevalence of HPV in this region is substantial; therefore, it is imperative to implement scientifically sound and rational clinical interventions such as vaccination. Routine cervical screening should be performed to prevent the development of cervical intraepithelial neoplasia resulting from persistent infection with high-risk HPV, particularly in women with gynecological diseases and those over 60 years old.

Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?

Uterine cervical intraepithelial abnormalities and cancer development may also depend upon biological problems that arise as a result of complex molecular disturbances within the vaginal space, in addition to the widely known causative effect of human papillomavirus (HPV) infection. Chronic oxidative stress is a consequence of oxygen reduction in the vaginal space. Reactive oxygen species (ROS) and free radicals are yet unrecognizable causative agents and are probably very important factors for cervical intraepithelial neoplasia (CIN) and cancer development. The intermediate compounds of oxygen reduction on these metabolic pathways are superoxide anion (), hydrogen peroxide (H2O2), hydroxide ions (OH-), and hydroxyl radical (HO˙). Considering these points, the aim of this work was to summarize how these compounds can damage all molecules, including DNA, of vulnerable metaplastic cervical epithelium. Finally, in some women with a poor immune defense system, ROS alone or accompanied by a high-risk HPV type may promote all levels of CIN and cancer development.

62P Role of IL6 (C-174G) polymorphism in the development of cervical intraepithelial neoplasia

62P Role of IL6 (C-174G) polymorphism in the development of cervical intraepithelial neoplasia

Cervical Microbiota Influences Cytokine Diversity in Cervical Intraepithelial Neoplasia among Rural Women in the Akyemansa District of Ghana.

In recent times, cervical dysbiosis which mostly causes and aggravates infections is highlighted for its role in immune modulation in cervical dysplasia, which promotes the shifting of Th1 phenotype immunity to Th2 phenotype immunity. This study therefore estimated and compared the levels of circulatory IL-4, IL-6, IL-10, TNF-α, and IFN-γ cytokines among adult women identified to have different grades of cervical intraepithelial neoplasia (CIN) and with cervicovaginal infection. A total of 157 participants were recruited from the Akyemansa District of Ghana, and cervical swabs and blood samples were taken. The Pap smear test, microbiological culture, and ELISA were employed for cytology analysis, bacteria isolation, and identification and estimation of IL-4, IL-6, IL-10, TNF-α, and IFN-γ cytokines, respectively. Overall, 14/157 (8.9%) had CIN with 7.6% having CIN 1 and 1.3% having CIN 2. The main predictor for CIN was age above 46 years (OR 11.16, 95% CI: 2.4-51.8). Bacterial vaginosis (p = 0.003) and Candida infection (p = 0.012) were significantly higher in CIN. Again, Staphylococcus aureus (60% vs. 17.6%, p = 0.005), Citrobacter sp. (40.0% vs. 13.2%, p = 0.017), and Morganella morganii (40.0% vs. 4.4%, p = 0.002) isolates were significantly higher in CIN-positive participants. IL-10 and TNF-α concentrations were elevated in participants with CIN 1+ (TNF-α NIL vs. CIN 1+ only, p < 0.05) while IL-6 was decreased among participants with CIN 1+. In the presence of vaginal infection, TNF-α decreased among CIN 1+ participants while IL-10 remained elevated. The findings of this study suggest that cervical dysbiosis causes immune suppression, which creates a suitable microenvironment for the development of CIN.

Peculiarities of the vagina microbiome and functional activity of epithelial cells in cervical intraepithelial neoplasia of the cervix in women of perimenapausal age

According to the data of the National Cancer Registry of Ukraine for 2021, the incidence of cervical cancer was 17.9 and the mortality rate was 7.9 per 100,000 female population. Therefore, in modern conditions, timely diagnosis, effective treatment and prevention of precancerous processes, which include cervical intraepithelial neoplasia (CIN) of the cervix, is one of the important tasks of a gynecologist. Women in perimenopause, who are traditionally considered to be at risk, deserve special attention.Today, there is information in the literature that multifactorial diseases account for 90–95% of all diseases, including cervical cancer. Epidemiological factors associated with human papillomavirus (HPV) prevalence are well known. The role of microbial-protozoan-viral associations in contributing to the occurrence of intraepithelial lesions and cervical cancer is being actively investigated.The objective: to assess the state of microbiocenosis and the functional activity of epithelial cells in perimenopausal women with recurrent CIN of the cervix.Materials and methods. 60 women of perimenopausal age with recurrent CIN of the cervix, which occurred after treatment with surgical methods (main group) and 38 healthy women of the appropriate age (control group) were examined. All patients were examined in accordance with the regulatory orders of the Ministry of Health of Ukraine, immunological studies, as well as determination of the electrokinetic activity of epithelial cells of the vagina and cervix according to the method of V. I. Shakhbazov in modification of V. O. Beniuk and co-authors.Results. The data of the anamnesis and clinical examination of the patients were evaluated, which allows to identify a risk group among women of perimenopausal age, according to the development of recurrent CIN of the cervix. During the study of the species composition of the vaginal microbiome in patients of the main group, a decrease in the number or complete absence of lactobacilli, a predominance of opportunistic vaginal flora in the cases with HPV infection was established. Peptostreptococci were found in 46.7 %, corynebacterial – in 61.7%, epidermal staphylococcus – in 66.7%, gardnerella – in 53.3%, Candida spp. – in 46.7% of cases and some specific pathogens versus the control group (7.9%, 23.7%, 10.5%, 15.8%, 5.3%, respectively). Also, in the main group, a significant decrease in the level of interferon-α (IFN) by 1.6 and IFN-γ by 1.9 times in blood serum was found.Studies of the electrokinetic activity of the epithelial cells of the vagina and cervix revealed a decrease of more than 2 times the corresponding indicators in the main group compared to the control group.Conclusions. In perimenopausal women with recurrent CIN of the cervix, profound violations of the vaginal microbiocenosis with the predominance of opportunistic flora, as well as insufficiency of interferonogenesis, decreased functional activity of epithelial cells, were determined.In general, based on the results of this study and modern scientific data, it can be concluded that the association of HPV with a violation of the vaginal microbiome in the conditions of physiological menopausal changes significantly increases the risk of development and recurrence of cervical intraepithelial lesions in women. Therefore, the existing screening methods and modern management of diagnosis of CIN of the cervix are important for the provision of high-quality medical care.

Human polyomavirus BKPyV and JCPyV serostatus has no impact on women´s human papillomavirus infection outcome.

Polyomaviruses have both structural and functional similarities with papillomaviruses. Accordingly, their role in human papillomavirus (HPV) associated malignancies has been studied with conflicting results. Our goal was to disclose any association between BK (BKPyV) and/or JC (JCPyV) polyomavirus serology and HPV data derived from Finnish women (327) in a 6-year prospective follow-up. Glutathione S-transferase fusion-protein-capture (ELISA) in combination with fluorescent bead technology was used to analyze antibodies to BKPyV and JCPyV. In the longitudinal setting, BKPyV or JCPyV serostatus was related to i) oral- and ii) genital low (LR)- and high risk (HR) HPV DNA detection, iii) HPV16 persistence at both these sites, iv) results of the Pap (Papanicolaou) smear taken at baseline, and v) development of incident CIN (cervical intraepithelial neoplasia) during the follow-up. Being BKPyV or JCPyV seropositive was not significantly associated with HPV seropositivity to either LR- or HR-genotypes, genital- or oral HPV DNA positivity, persistence of genital- or oral HPV16 infection, grade of Pap smear, or development of incident CIN. Thus, the present study could not provide any confirmation to the concept that co-infections by HPyV and HPV have interactions that impact on the clinical manifestations or outcomes of HPV infections either in the genital tract or in the oral mucosa.

Dysbiotic Co-Factors in Cervical Cancer. How the Microbiome Influences the Development of Cervical Intraepithelial Neoplasia (CIN).

Human papillomavirus (HPV) infection is a necessary but not sufficient condition for the development of cervical cancer. The dysbiotic shift in the cervicovaginal microbiome appears to be a major co-factor in carcinogenesis. New analytical methods, such as next-generation sequencing (NGS), can be used to detect all of the vaginal microorganisms present and therefore identify individual therapeutic options. The relationship of bacterial vaginosis and carcinogenesis, as well as possible indications for the use of microbiome analysis, will be discussed.

Analysis of the Prevalence and Quantification of viral load of different human papillomavirus types in Turkish women population

Persistent infection with high-risk (HR) Human Papilloma Virus (HPV) genotypes has been shown to play a significant role in the development of cervical intraepithelial neoplasia (CIN) and CC (cervical cancer). The present study aimed to determine the distribution and quantification of viral load of HPV genotypes in numerous genital samples obtained from women undergoing routine gynaecological care in different regions of Turkey. HPV typing was done by HPV QUANT-21 Quantitative RT-PCR Kit®, which is intended for the specific identification and quantification of low-risk (HPV 6, 11, 44) and high-risk (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) from female subjects in Turkey. From the total of 5975 samples, 2777 were positive for at least one HPV genotype, with an overall frequency of 46.4%. 1695 patients were positive for only one or more LR-HPV genotypes (61%) and 812 patients were positive for one or more HR-HPV genotypes (29%). The frequency of LR-HPV genotypes was 31.4%, while the frequency of HR-HPV genotypes was 118.8%. Our tecnology had a positive advantage to calculate the concentration of each genotypes. Although genotype 52 ranked fifth in frequency, it showed the highest mean concentration, with a value of 5.38 log (copies/sample). The presence and genotype of viruses before HPV vaccination have also gained importance. The data obtained would provide guidance for prevention strategies, mainly of vaccination. We decided to add a new estimate to the effectiveness of currently available HPV vaccines and the development of screening programs to prevent and decrease the incidence of CC in Turkey. Further studies would be planned to measure and define the high infection level that can lead to the development of cervical neoplasia. Using this tecnology could give us a clinical desicion to degree the cytological changes.

Aerobic Vaginitis: is Enterococcus faecalis Another Risk Factor in the Progression of Cervical Intraepithelial Neoplasia to Cervical Cancer—Literature Review

Objective: The aim of our review article is to show Enterococcus faecalis (E. faecalis) as a risk factor of cervical cancer. Mechanism: Aerobic vaginitis (AV) is the absence of a balance of vaginal flora containing aerobic and intestinal pathogens, varying degrees of vaginal inflammation and immature epithelial cells. The causes of AV responsible for inflammatory changes are: E. faecalis, Esherichia coli, group B streptococcus and Staphylococcus aureus. The pathogenic effect of aerobic microorganisms such as E. faecalis shows that it causes spontaneous abortion, premature birth, puerperal sepsis, abscesses, and urinary tract infections. Findings in Brief: AV caused by E. faecalis is more common in low-grade and high-grade cervical intraepithelial neoplasia (CIN) than in women with a normal Pap test and is thought to contribute to the progression of cervical cancer. E. faecalis produces hydrogen superoxide which causes chromosomal instability in intestinal epithelial cell infection, which is considered a key factor in the carcinogenic process. The presence of the Human papilloma virus (HPV) 16 gene and genome in E. faecalis in cervical cancer biopsy material leads to a specific link that may be a risk factor in the progression of CIN toward cancer. The presence of HPV in this bacteria can lead to persistent HPV infection, CIN development and progression to cervical cancer. Conclusions: Increased vaginal pH, lactobacilli deficiency, and the ability of E. faecalis to contain HPV-16 in episomal form in E. faecalis-induced AV could be key promoters of persistence and proliferation of cervical HPV as a risk factor in development of CIN and cervical cancer.

16P The role of IL-8 gene polymorphism (845 T/C) in the development of cervical intraepithelial neoplasia

IL-8 gene polymorphisms are involved in the carcinogenesis of many malignant neoplasms, but their role in the development of cervical cancer (CC) has not been fully elucidated. The aim of the study was to evaluate the relationship between the presence of IL-8 gene polymorphism (845 T/C) and the development of severe cervical intraepithelial neoplasia (CIN) and cervical cancer.

Dysbiosis of Cervical and Vaginal Microbiota Associated With Cervical Intraepithelial Neoplasia.

Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.

Genetic variations in the long control region of human papillomavirus type 16 isolates from India: implications for cervical carcinogenesis.

Introduction. Infection with high-risk human papillomavirus (HPV) types, specifically HPV type 16 (HPV16), is considered to be the most important risk factor in the development of cervical intraepithelial neoplasia and cancer. The long control region (LCR) is a noncoding region that comprises approximately 10 % of the HPV genome and contains regulatory elements for viral transcription and replication. Sequence variations in LCR may impact on the replication efficiency and oncogenic potential of the virus.Gap statement. Studies documenting variations in LCR of HPV16 isolates pertaining to cervical neoplastic status in India are limited.Aim. The present study was designed to characterize variations in the LCR of Indian isolates of HPV16 and study their association with cervical disease grades.Methodology. The LCR was amplified and sequenced from HPV16 positive cervical samples belonging to different cervical disease grades. Sequences were aligned to identify variations and potential transcription factor binding sites (TFbs) were predicted using the JASPAR database in addition to phylogenetic studies.Results. Among the 163 HPV16 isolates analysed, 47 different nucleotide variations were detected in the LCR, of which 25 are reported for first time in Indian isolates. Point mutations were detected in 35/54 (64.8 %) samples with normal cervical status, 44/50 (88 %) samples with low-grade cervical disease and 53/59 (89.8 %) samples with high-grade cervical disease. Variations T6586C, G6657A and T6850G were significantly associated with high-grade cervical status. Thirteen LCR variations were detected in the binding sites for CEBPB, ETS1, JUN, MYB, NFIL3, PHOX2A and SOX9 transcription factors.Conclusion. The present study helped to identify unique variations in the LCRs of HPV16 Indian isolates. The variations in the A4 sub-lineage were significantly associated with high-grade disease status. The isolates belonging to the A4 and D3 sub-lineages harboured mutations in putative TFbs, implying a potential impact on viral replication and progression to cervical cancer.

Environmental Cofactors Associated with the Development of Cervical Intraepithelial Neoplasia and Cervical Cancer

El Cáncer Cervicouterino (CaCu) es una de las principales causas de morbimortalidad a nivel mundial y en México. Esta enfermedad requiere de la presencia del Virus del Papiloma Humano (VPH) para su progreso a Neoplasia Intraepitelial Cervical (NIC), pero además de otros cofactores. Entre estos se han propuesto los cofactores ambientales o exógenos, los de tipo viral, del huésped o intrínsecos y los de tipo social. Esta revisión aborda los de tipo ambiental, entre ellos están: el uso de anticonceptivos hormonales orales, hábito tabá-quico, exposición al humo de biomasa, la dieta, trauma cervical, Inicio de Vida sexual a Edad Temprana (IVSET), múltiples parejas sexuales, coinfección con otras enfermedades de transmisión sexual, no utilización del preservativo y la circuncisión de la pareja. Los cofactores modulan el progreso de los distintos grados de NIC a CaCu, por ello es importantes conocerlos y analizar de qué manera influyen en la aparición esta patología. Palabras Clave: Virus del Papiloma Humano, Cáncer Cervicouterino, Cofactores ambientales

The Role of IL-2, IL-4, IL-10 and IFN-&amp;lt;i&amp;gt;γ&amp;lt;/i&amp;gt; Cytokines Expression in the Microenvironment of Cervical Intraepithelial Neoplasia

Objective: To investigate the role of IL-2, IL-4, IL-10 and IFN-γ cytokines in the microenvironment of cervical intraepithelial neoplasia. Methods: 180 patients participating were enrolled in this trial, where 50 cases are in control group, 50 cases are in low-grade squamous intraepithelial lesion (LSIL) group, 50 cases are in high-grade squamous intraepithelial lesion (HSIL) group, and 30 cases have cervical carcinoma. ELISA methods are used to detect the expression of IL-2, IL-4, IL-10 and IFN-γ in the lavage fluid, and all data is analyzed using one-way analysis of variance. Results: The expression of IL-2 and IFN-γ in cervical lavage fluid gradually decreases with the aggravation of the lesion. The expression of IL-4 and IL-10 increases by the aggravation of pathological changes. There were statistically significant differences in IL-2 level among the four groups. IFN-γ levels are significantly different between the cervical cancer group and the other groups, also between HSIL and LSIL group, and between HSIL and the control group, but no statistically significant difference was observed in IFN-γ e between LSIL and the control group. The expressions of IL-4 and IL-10 between the cervical cancer group and the other groups were significantly different, and also between HSIL and the control group. But there was no statistically significant difference between LSIL and the control group, HSIL and LSIL. Conclusion: The cytokines of IL-2, IL-4, IL-10 and IFN-γ in the microenvironment of the cervix play an important role in the occurrence and development of cervical intraepithelial neoplasia. This study may provide the evidence for diagnosis and treatment of cervical intraepithelial neoplasia.

Abstract PR-14: A synergy between the vaginal microbiome and HPV may have explanatory value for racial disparities in risk of pre-cervical cancer

Abstract The vaginal microbiome (VMB) is suggested to be a key player in high-risk Human Papilloma Virus (HPV) infection persistence, leading to the development of cervical intraepithelial neoplasia (CIN). While it is generally accepted that the VMB of women with CIN differs from that of healthy women, the VMB composition before a woman develops CIN has not been well studied. Moreover, no studies have evaluated the role of self-reported race on the VMB-CIN relationship, despite reports that the VMB of non-Latina Black (Black) women generally exhibits increased microbial diversity (often associated with HPV tumorigenesis) and lower prevalence of taxa such as Lactobacillus (reported to have an inverse association with severity of cervical abnormalities) compared to their non-Latina White (White) counterparts. Black women have higher HPV prevalence than Whites (39% vs. 24%), and more persistent HPV infections (601 days vs. 316 days, respectively), despite having a similar number of HPV infections to Whites. This suggests that factors beyond multiple HPV exposures sustain the infection. We hypothesize that HPV and the VMB may interact differently by race, to promote development of CIN. Methods: We used 16S-RNA profiles from the VMB of 3,050 consented women visiting the Virginia Commonwealth University clinics for their annual routine exam between August 2009 and November 2013. Of these, 259 had evidence of subsequent CIN after the VMB sample collection, through October 2020. The VMB profiles were characterized into three groups as “Lactobacillus (L) crispatus” group (including L. crispatus, L. gasseri and L. jensenii), “L. iners” group and “Other” based on a priori knowledge of profiled taxa. The “Other” subgroup included taxa, such as G. vaginalis, A vaginae, and others usually associated with bacterial vaginosis-like states. We used self-reported health histories, confirmed by electronic health records to determine HPV status and obtain other socio-demographic information. Multivariable logistic regression models were adjusted for age, smoking, VMB, HPV, marital and pregnancy status. Results: The cohort was mainly Black (70%), and the VMB prevalence by group was 19%, 30% and 51% for L. crispatus, L. iners, and Other, respectively. Twelve percent reported having an HPV diagnosis in the past, and 302 (10%) women developed CIN during an average of 3.6 years of follow-up (259 with CIN 1/2 and 43 with CIN3+). In crude analyses, risk of CIN was 80% higher for Black women (RR=1.8, p&amp;lt;0.0001) compared to Whites. However, a significant interaction between HPV status and the VMB revealed that the risk of a CIN diagnosis for HPV+ Black women with the “Other” VMB subtype, is five-fold (RR=5.3, p&amp;lt;0.40) the risk for Whites. Conclusions: These preliminary results suggest that interactions between the VMB and HPV may account for the differential risk of CIN by race. If replicated in further analyses, VMB profiling could help elucidate the basis of CIN racial disparities. Citation Format: Katherine Y. Tossas, Jinlei Zhao, Myrna Serrano, Jerome Strauss, Victoria Seewaldt, Gregory Buck, Robert A. Winn. A synergy between the vaginal microbiome and HPV may have explanatory value for racial disparities in risk of pre-cervical cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-14.

Bacterial vaginosis, cervical Human Papillomavirus infection and cervical cytological abnormalities in adult women in Central Brazil: A cross-sectional study

Introduction: Bacterial vaginosis is the most common cause of vaginal discharge and occurs when there is an imbalance in the vaginal microbiota, predominantly composed of Lactobacillus spp. Human Papillomavirus is the most common sexually transmitted virus in the world. Persistent infection with high-risk Human Papillomavirus genotypes is the main cause of the development of cervical intraepithelial neoplasia and cervical cancer. Objective: To investigate the association between bacterial vaginosis and cervical Human Papillomavirus infection and between bacterial vaginosis and cervical cytological abnormalities in adult women. Methods: Cross-sectional study carried out in a gynecology outpatient clinic of the public health network. A total of 202 women were included in the study and underwent gynecological examination with cervical specimen collection. Cervical cytopathological examinations and bacterioscopy by the Nugent method were performed to identify bacterial vaginosis, and PCR and reverse hybridization were carried out for Human Papillomavirus detection and genotyping. Bivariate analysis was performed to investigate the association between bacterial vaginosis and cervical Human Papillomavirus infection, and between bacterial vaginosis and cervical cytological abnormalities. The odds ratio was calculated, with the respective 95% confidence intervals (95%CI) and 5% significance level (p≤0.05). Results: The prevalence of bacterial vaginosis was 33.2% (67/202), the prevalence of cervical Human Papillomavirus infection was 38.6% (78/202) and the prevalence of cervical cytological abnormalities was 6.0% (12/202). Bivariate analysis showed no significant association between bacterial vaginosis and cervical Human Papillomavirus infection (OR 0.69; 95% CI 0.37–1.27; p=0.23), or between bacterial vaginosis and cervical cytological abnormalities (OR 0.65; 95%CI 0.17–2.50; p=0.54). Conclusion: In this study, bacterial vaginosis did not represent a risk factor for cervical Human Papillomavirus infection or for the presence of cervical cytological abnormalities in the investigated adult women.