Severity Of Cervical Intraepithelial Neoplasia Research Articles

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China.

Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.

Escherichia coli and HPV16 coinfection may contribute to the development of cervical cancer

ABSTRACT Persistent human papillomavirus HPV infection is a necessary but insufficient condition for cervical cancer. Microorganisms are crucial environmental factors in cancers susceptibility and progression, recently attracting considerable attention. This study aimed to determine the infection status and relationship between high-risk HPV (HR-HPV) and lower genital tract infectious pathogens in cervical cancer and its precursors. From a retrospective and a prospective cohort analysis, Escherichia coli (E. coli) dominated the pathogens isolated from cervical discharges, and an isolation rate uptrend has been shown recently. HPV16 and E. coli’s coinfection rate gradually increased with the severity of cervical intraepithelial neoplasia. The adhesion and invasion abilities of the isolated E. coli to HPV16-positive SiHa cells were evaluated in vitro. The TCGA database and cervical tissues samples analysis showed that IL-10 was upregulated in cervical cancer. IL-10 expression levels increased in tissue samples with the severity of cervical cancer and its precursors with HPV16 and E. coli coinfection. Although no significant changes in IL-10 production were observed in the co-culture supernatant, we hypothesized that Treg immune cells in the tumour microenvironment might be responsible for the local IL-10 upregulation, according to our data showing Foxp3 upregulation and an upward trend with the cervical intraepithelial neoplasia grading to cancer and tumours with E. coli and HPV16 coinfection. Our data provide insights into the possible role of E. coli in cervical cancer progression and suggest that the application of HPV and E. coli screening programs may be an effective strategy to relieve the burden of cervical cancer and its precursor lesions.

Correlation between cervical thickness and histological severity of cervical intraepithelial neoplasia: A transvaginal ultrasound investigation

Correlation between cervical thickness and histological severity of cervical intraepithelial neoplasia: A transvaginal ultrasound investigation

The Relationship between Furin and Chronic Inflammation in the Progression of Cervical Intraepithelial Neoplasia to Cancer: A Cross-Sectional Study.

The current study aimed to delineate the relationship between furin and chronic inflammation while cervical intraepithelial neoplasia progresses to cancer. This cross-sectional study included 81 women who required colposcopic examinations. The study groups were formed based on pathological results: Group I included women with cervical intraepithelial neoplasia (CIN) I (n = 30); Group II included women with CIN II-III (n = 28); and Group III included women with cervical cancer (CC) (n = 23). Furin, ki-67, and p16 levels were evaluated based on immunostaining intensity. The inflammatory indices were calculated in parallel with the literature from routine blood samples retrieved within one week before the procedure. Furin expression gradually increased from CIN I to CIN II-III and from CIN II-III to CC, respectively (p < 0.001, p = 0.005). NLR, MLR, PLR, and SII were significantly higher in the CC group (p < 0.001). ROC curve analysis unveiled that NLR, MLR, PLR, and SII predicted the presence of CC with a cutoff value of 2.39 for NLR (sensitivity: 91.3%, specificity: 63.8%, AUROC: 0.79, p < 0.001); a cutoff value of 0.27 for MLR (sensitivity: 78.3%, specificity: 72.4%, AUROC: 0.77, p = 0.009); a cutoff value of 123 for PLR (sensitivity: 100%, specificity: 41.4%, AUROC: 0.70, p = 0.04); and a cutoff value of 747 for SII (sensitivity: 69.6%, specificity: 90.7%, AUROC: 0.71, p = 0.014). Furin expression increased gradually in parallel with the severity of cervical intraepithelial neoplasia. The inflammatory indices were higher in the presence of CC and denoted a good discrimination ability for predicting cervical cancer.

Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection

Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection.Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry.53 women were HPV+ against 127 women HPV−. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries.In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.

Shotgun Lipidomics for Differential Diagnosis of HPV-Associated Cervix Transformation.

A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of cervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix.

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Cervical intraepithelial neoplasia and the risk of spontaneous preterm birth: A Dutch population-based cohort study with 45,259 pregnancy outcomes.

BackgroundExcisional procedures of cervical intraepithelial neoplasia (CIN) may increase the risk of preterm birth. It is unknown whether this increased risk is due to the excision procedure itself, to the underlying CIN, or to secondary risk factors that are associated with both preterm birth and CIN. The aim of this study is to assess the risk of spontaneous preterm birth in women with treated and untreated CIN and examine possible associations by making a distinction between the excised volume of cervical tissue and having cervical disease.Methods and findingsThis Dutch population-based observational cohort study identified women aged 29 to 41 years with CIN between 2005 and 2015 from the Dutch pathology registry (PALGA) and frequency matched them with a control group without any cervical abnormality based on age at and year of pathology outcome (i.e., CIN or normal cytology) and urbanization (<100,000 inhabitants or ≥100,000 inhabitants). All their 45,259 subsequent singleton pregnancies with a gestational age ≥16 weeks between 2010 and 2017 were identified from the Dutch perinatal database (Perined). Nineteen potential confounders for preterm birth were identified. Adjusted odds ratios (ORs) were calculated for preterm birth comparing the 3 different groups of women: (1) women without CIN diagnosis; (2) women with untreated CIN; and (3) women with treated CIN prior to each childbirth.In total, 29,907, 5,940, and 9,412 pregnancies were included in the control, untreated CIN, and treated CIN group, respectively. The control group showed a 4.8% (1,002/20,969) proportion of spontaneous preterm birth, which increased to 6.9% (271/3,940) in the untreated CIN group, 9.5% (600/6,315) in the treated CIN group, and 15.6% (50/321) in the group with multiple treatments. Women with untreated CIN had a 1.38 times greater odds of preterm birth compared to women without CIN (95% confidence interval (CI) 1.19 to 1.60; P < 0.001). For women with treated CIN, these odds 2.07 times increased compared to the control group (95% CI 1.85 to 2.33; P < 0.001). Treated women had a 1.51 times increased odds of preterm birth compared to women with untreated CIN (95% CI 1.29 to 1.76; P < 0.001). Independent from cervical disease, a volume excised from the cervix of 0.5 to 0.9 cc increased the odds of preterm birth 2.20 times (37/379 versus 1,002/20,969; 95% CI 1.52 to 3.20; P < 0.001). These odds further increased 3.13 times and 5.93 times for women with an excised volume of 4 to 8.9 cc (90/724 versus 1,002/20,969; 95% CI 2.44 to 4.01; P < 0.001) and ≥9 cc (30/139 versus 1,002/20,969; 95% CI 3.86 to 9.13; P < 0.001), respectively. Limitations of the study include the retrospective nature, lack of sufficient information to calculate odds of preterm birth <24 weeks, and that the excised volume could only be calculated for a select group of women.ConclusionsIn this study, we observed a strong correlation between preterm birth and a volume of ≥0.5 cc excised cervical tissue, regardless of the severity of CIN. Caution should be taken when performing excisional treatment in women of reproductive age as well as prudence in case of multiple biopsies. Fertile women with a history of performing multiple biopsies or excisional treatment for CIN may benefit from close surveillance during pregnancy.

A prognostic value of CD45RA+, CD45RO+, CCL20+ and CCR6+ expressing cells as \u2018immunoscore\u2019 to predict cervical cancer induced by HPV

The interplay between cervical cancer (CC) and immune cells, mainly intratumoral lymphocytes, has a pivotal role in carcinogenesis. In this context, we evaluated the distribution of CD45RA+ and CD45RO+ cells as well as CCR6+ and CCL20+ cells in intraepithelial (IE) and marginal stroma (MS) areas from cervical intraepithelial neoplasia (CIN) I–III, and CC as ‘immunoscore’ for HPV-induced CC outcome. We observed increased CD45RA+ and CD45RO+ cells distribution in IE and MS areas in the CC group compared to CIN groups and healthy volunteers. Interestingly, there is a remarkable reduction of CCL20+ expressing cells distribution according to lesion severity. The CC group had a significant decrease in CCL20+ and CCR6+-expressing cells distribution in both IE and MS areas compared to all groups. Using the ‘immunoscore’ model, we observed an increased number of women presenting high CD45RA+/CD45RO+ and low CCL20+/CCR6+ ‘immunoscore’ in the CC group. Our results suggested a pattern in cervical inflammatory process with increasing CD45RA+/CD45RO+, and decreasing CCL20+/CCR6+ expression in accordance with CIN severity. Taken together, these markers could be evaluated as ‘immunoscore’ predictors to CC response. A more comprehensive analysis of longitudinal studies should be conducted to associate CD45RA+/CD45RO+ and CCL20+/CCR6+ ‘immunoscore’ to CC progression and validate its value as a prognosis method.

Vaginal Microbiome-Based Bacterial Signatures for Predicting the Severity of Cervical Intraepithelial Neoplasia.

Although emerging evidence revealed that the gut microbiome served as a tool and as biomarkers for predicting and detecting specific cancer or illness, it is yet unknown if vaginal microbiome-derived bacterial markers can be used as a predictive model to predict the severity of CIN. In this study, we sequenced V3 region of 16S rRNA gene on vaginal swab samples from 66 participants (24 CIN 1−, 42 CIN 2+ patients) and investigated the taxonomic composition. The vaginal microbial diversity was not significantly different between the CIN 1− and CIN 2+ groups. However, we observed Lactobacillus amylovorus dominant type (16.7%), which does not belong to conventional community state type (CST). Moreover, a minimal set of 33 bacterial species was identified to maximally differentiate CIN 2+ from CIN 1− in a random forest model, which can distinguish CIN 2+ from CIN 1− (area under the curve (AUC) = 0.952). Among the 33 bacterial species, Lactobacillus iners was selected as the most impactful predictor in our model. This finding suggests that the random forest model is able to predict the severity of CIN and vaginal microbiome may play a role as biomarker.

Analysis of the role of the human papillomavirus 16/18 E7 protein assay in screening for cervical intraepithelial neoplasia: a case control study

BackgroundCervical cancer is the second-most common gynecological cancer, early screening plays a key role in the diagnosis and treatment of cervical intraepithelial neoplasia (CIN). Sustained E7 protein expression is the pathological basis for CIN and cervical cancer.MethodsWe collected the cervical cell samples of women who visited the gynecological clinic of Peking Union Medical College Hospital between September 2018 and September 2019 and submitted them to the high-risk human papillomavirus (Hr-HPV) test. We performed a magnetic particle–based chemiluminescence enzyme immunoassay to analyze the HPV16/18 E7 protein level in CIN of different severities and compared the results with those of cervical pathology (gold standard) and the HPV test.ResultsThe positive rate of HPV16/18 E7 protein increased with the severity of CIN: 26.6% in normal tissue, 58.3% in CIN1, and 70.6% in CIN2 or higher (CIN2+). For CIN2+, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the E7 protein were 70.6, 67.9, 52.2, and 82.3%, respectively. These values of the HPV test were 86.8, 44.5, 43.7, and 87.1%, respectively. With the combination of the E7 protein assay and HPV test, the specificity for diagnosing CIN2+ was 78.1%, which was significantly higher than that of the HPV test alone.ConclusionsHPV16/18 E7 protein level is correlated with the severity of CIN and has a high concordance rate with the pathological result. For cervical cancer screening, the combination of HPV16/18 E7 protein assay and HPV test improves the CIN diagnostic specificity, detection rate, and detection accuracy.

Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

BackgroundIn this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts.MethodsThe vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3–4) using Illumina MiSeq.ResultsHPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs.ConclusionsThis work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

REVIEW OF MEDICAL DESCRIPTION OF CERVICAL CYTOLOGY

Cervical cancer is a malignant neoplasm of the cervical area or cervix which may present with the vaginal bleeding but symptoms may be absent until the cancer gets in advanced stage. Dysplasia seen on cervical biopsy uses the term cervical intraepithelial neoplasia (CIN) and is grouped into mild (CIN-1), moderate (CIN-2) and severe (CIN-3). The severity of CIN depends upon cellular disorganization, cellular immaturity, increased mitotic activity and nuclear abnormalities. The nuclear atypia, extent of mitotic activity and immature cellular proliferations identifies the degree of dysplasia. Thus, epithelial thickness which shows differentiation is the useful feature in decision about severity of CIN. Treatment of this cancer may be ablative and/ or excision. Cryotherapy is a reasonable treatment of CIN-1 and CIN-2 but not of CIN-3 which is severe cervical carcinoma. Burning the TZ-transformation zone (Electro diathermy) destroys the tissue more effectively than that of cryotherapy but it usually requires general anesthesia, however laser cold coagulations technique requires local anesthesia usually. Laser TZ Excision compromises the fertility. Knife cone biopsy is used as a preferred treatment for removal of abnormal cervical cells. Now the cone biopsy is generally performed using the laser surgery. Early diagnosis of cervical cancer is very necessary for better control and treatment of it. For early phases of cervical carcinoma, the cryotherapy is very reasonable, however in case of late stage of the disease laser methods are used alone or on combination. Therapy will be termed successful if cytology remains negative after at least six months of its treatment.

The Relationship between the Serum Level of Selenium and Cervical Intraepithelial Neoplasia: A Comparative Study in a Population of Nigerian Women

Objective:To determine the relationship between the serum level of selenium and cervical intraepithelial neoplasia (CIN).Methods:A case controlled study that compared the serum level of selenium in 45 women with CIN (cases) to 45 women (age matched controls) with normal cervical cytology. Socio-demographic data and information on known risk factors for cervical cancer among the sample was compared between both groups using inferential statistics.Results:There was no significant difference in the mean selenium values between the cases and controls [p- 0.076, 95% CI (-15.08 – 0.76)]. However, subgroup analysis showed a statistically significant difference between patients with normal cervical cytology, CIN I, II and III (p= 0.021). In addition, there was also significant difference in the selenium level between women with normal cervical cytology and CIN III (p value = 0.016) with a significant inverse linear trend (p= 0.025).Conclusion:With increasing severity of CIN, a significant reduction in the level of selenium in serum was observed. This reducing value of serum selenium, a surrogate marker for increased oxidative stress, may be important factor for the development of persistent HPV infection and in particular high grade CIN III lesions. This observation requires further research.

[Effect of hnRNP K and its interaction with HPV16 on cervical intraepithelial neoplasia].

Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavirus 16 (HPV16) on cervical intraepithelial neoplasia (CIN). Methods: The participants included 67 women with normal cervix (NC), 69 women with CINⅠ and 68 women with CINⅡ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province, from June 2014 to June 2015. A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions. Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected. The infection status of HPV16 was detected by flow-through hybridization. The protein expression levels of hnRNP K were evaluated by Western blot. SPSS 23.0 software was used to collate and analyze the data. To study the differences in demographic characteristics, related factors, hnRNP K protein and HPV16 infection among NC, CINⅠand CINⅡ/Ⅲgroups, χ(2) test, trend χ(2) test, and Kruskal-Wallis H test were conducted. Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method. The OR and its 95%CI of hnRNP K, HPV16 and CIN were calculated by using the unconditional logistic regression models. Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators. Results: HPV16 infection rates were 10.4% in women with normal cervix, 14.5% in women with CINⅠ and 41.2% in women with CINⅡ/Ⅲ, respectively. The differences among three groups were significant (P<0.001). Moreover, the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend χ(2)=18.512, P<0.001). The differences in protein expression of hnRNP K among three groups were significant (H=48.138, P<0.001) and the expressionincreased with the development of cervical lesionss (trend χ(2)=21.765, P<0.001). Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CINⅡ/Ⅲ group compared with normal group (API=0.639, 95%CI: 0.083-1.196). In contrast, no such additive effect was found in CINⅠ group. Conclusions: HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia. There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CINⅡ/Ⅲ.

Analysis of clinical factors correlated with the accuracy of colposcopically directed biopsy.

Many factors affect the accuracy of colposcopically directed biopsy (CDB). This study aimed to compare the histological results of CDB with those of cone specimens and to determine clinical factors associated with the accuracy of CDB in defining the extent and severity of cervical intraepithelial neoplasia. We studied 513 patients diagnosed with cervical intraepithelial neoplasia by CDB who underwent conization between September 2012 and December 2016. We retrospectively evaluated the agreement between histological results on biopsies and cone specimens and analyzed factors influencing the accuracy of the results. The overall agreement between the histological results on biopsy and the corresponding cone specimens was 74.1%; underestimation occurred in 6.4% of cases. The agreement between histological results on biopsy and cone specimen was 54.5% for low-grade lesions, 78.2% for high-grade lesions, and 28.9% for microinvasive cervicalcancer. The overall agreement between high-grade cytology and the final histological diagnosis was 86.7%. By univariate analysis, patient age (p=0.026), menopausal status (p=0.018), type of transformation zone (p=0.003), number of biopsies (p=0.002), and cone width (p=0.015) were found to be associated with the accuracy of CDB. However, multivariate logistic regression revealed that cone width (p=0.044) was the only independent factor correlated with CDB accuracy. Our data suggest that old age (≥50), postmenopausal status, and transformation zone type 3 might be positively associated with the under-diagnosis of CDB. Three or more biopsies and cone width ≥21mm might improve CDB accuracy. However, cone width was the only independent factor correlated with CDB accuracy.

[Interaction between polycyclic aromatic hydrocarbons and p16, FHIT gene CpG island methylation in patients with cervical intraepithelial neoplasias].

Objective: To explore the effect of polycyclic aromatic hydrocarbons (PAHs) and p16, FHIT gene CpG island methylation, as well as their interaction in cervical intraepithelial neoplasias. Methods: Objects of this study were from a cohort of cervical lesions study in Yangqu county of Shanxi province. All the patients were diagnosed pathologically, that including 83 patients with high-grade cervical intraepithelial neoplasia (CINⅡ/Ⅲ), 86 patients with low-grade cervical intraepithelial neoplasia (CINⅠ) and another 91 women under normal cervical (NC) condition. 1-hydroxy pyrene in the urine was detected by high performance liquid chromatography (HPLC) while CpG island methylation status of tumor suppressor gene p16 and FHIT were measured by methylation-specifc polymerase chain reaction (MSP). Data were analyzed with Kruskal-Wallis H test, chi-square test and trend of chi-square test. Logistic regression models were used to estimate the odds ratio (OR) and corresponding 95% confidence intervals (95%CI) between influencing factors and the cervical disease by using the SPSS statistical software (version 20.0). The interaction under study was evaluated by using the generalized multifactor dimensionality reduction (GMDR) model. Results: Level of 1-hydroxy pyrene (H=50.743, P<0.001) and the high exposure rate of 1-hydroxy pyrene (trend χ(2)=20.146, P<0.001) were gradually increasing along with the severity of cervical intraepithelial neoplasia. The CpG island methylation rates of p16, FHIT in CINⅠand CINⅡ/Ⅲ group were higher than that in NC group, and gradually increasing along with the severity of cervical intraepithelial neoplasia (trend χ(2)=9.75, P=0.002; trend χ(2)=10.39, P=0.001). Results from the GMDR model showed that interaction existed among the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16, FHIT in CINⅠ and CINⅡ/Ⅲ group. Conclusion: Under the high exposure of 1-hydroxy pyrene and the CpG island methylation of p16, FHIT appeared to have increased the risk of cervical intraepithelial neoplasia and causing synergistic effect in cervical intraepithelial neoplasia.

[Modern biomarkers for precancerous lesions of the uterine cervix : Histological-cytological correlation and use].

The correlation between the cytological findings from the PAP smear and the histological outcome in cases where the cytological findings must be histologically verified, is an integral component of the German screening program for cervical cancer. These data are collected nationwide as part of abenchmarking process by the individual Associations of Statutory Health Insurance Physicians (KV) in the federal states and reported to the National Association of Statutory Health Insurance Physicians (KBV) in Berlin. In most cases there is agood correlation between cytology and histology but in some cases either adifferent grade of severity of cervical intraepithelial neoplasia (CIN) is found or the histological findings are negative. The reasons for alack of correlation can be insufficient sampling in the cytology or the biopsy or amisinterpretation of the individual findings. Although the findings from H&E sections are considered to be the gold standard in the histological evaluation, it has long been known that the interobserver agreement in these preparations is only moderate. Asignificant improvement becomes apparent, firstly by the classification of cervical cancer precursors into low-grade and high-grade groups and secondly by the targeted application of biomarkers, in particular p16 and Ki-67, according to the recommendations of the lower anogenital squamous terminology standardization (LAST) project. The biomarkers p16 and Ki-67 should be used in the differential diagnostics between reactive and reparative alterations and for further differentiation of a CIN grade 2 but not to confirm aCIN grade 3. It is still unclear whether p16 is suitable as aprognostic marker for low-grade lesions.

Characterisation of the vaginal microbiome in cervical intraepithelial neoplasia

BackgroundPersistent infection with oncogenic human papillomavirus (HPV) is necessary for the development of cervical cancer. Although evidence indicates that the vaginal microbiome can have a functional role in the persistence or regression of HPV infections, this possibility has yet to be described in women with cervical intraepithelial neoplasia (CIN). We aimed to test the hypothesis that increasing microbiome diversity is associated with increasing CIN severity. MethodsVaginal swabs were collected, and vaginal microbiome characterised by 16S rRNA gene sequencing (MiSeq, Illumina, San Diego, CA, USA). Women were categorised according to disease severity (invasive cervical cancer [ICC], high-grade squamous intraepithelial lesions [HSIL], low-grade squamous intraepithelial lesions [LSIL], and healthy controls) and HPV status and genotype. Multivariate modelling of sequence data was used to examine bacterial species classification data, and correlated to disease severity and HPV status and genotype. FindingsHierarchical clustering analysis of bacterial species data revealed an association between increased disease severity and increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp (community state type CST IV), irrespective of HPV status (2 [10%] of 20 controls, 11 [21%] of 52 LSIL, 25 [27%]of 92 HSIL, ICC 2 [40%] of 5 ICC). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in women with HSIL was characterised by higher relative abundance of Sneathia sanguinegens (p<0·01), Anaerococcus tetradius (p<0·05), and Peptostreptococcus anaerobius (p<0·05), and lower levels of L jensenii (p<0·01) compared with women with LSIL. InterpretationWe show that women with CIN have a more diverse Lactobacillus-depleted vaginal microbiome, compared with healthy women. This finding supports previous reports indicating that a dysbiotic microbiome could be involved in HPV persistence. The vaginal microbiome can have a role in carcinogenesis and warrants further investigation. Future therapeutic strategies might allow modulation of the vaginal microbiome towards a vaginal community structure that promotes HPV clearance. FundingImperial College Healthcare Charity, British Society for Colposcopy and Cervical Pathology.