Stratified mucin-producing intraepithelial lesion (SMILE) is a rare high-grade cervical precancerous lesion designated a variant of adenocarcinoma in situ (AIS) in the WHO classification. We aimed to ...determine HPV genotypes, immunohistochemical phenotype and mucin presence in SMILE. Between 2010 and 2018, SMILE was diagnosed in 34 out of 6958 (0.5%) cervical biopsies, in 23 patients. Twenty-six tissue samples from twenty-one patients were available for further analysis, including 13 with SMILE alone, 12 with SIL and/or AIS and one with HSIL, AIS and endocervical adenocarcinoma. HPV genotyping was performed using the Seegene Anyplex II HPV 28 assay. Of the 26 samples, a single HPV genotype was identified in the majority of cases (n = 22), including 12/13 SMILEs associated with SIL/AIS. All but one were high-risk HPV genotypes (23/24; 96.8%). We identified seven different HPV genotypes, the most common being HPV16 (n = 10; 43.5%), HPV18 (n = 8, 34.8%) and HPV 31 (n = 5, 21.7%). All SMILEs showed a strong positive reaction to p16, CK7, CK19 and high Ki67 expression comparable to adjacent HSIL and/or AIS if present. SMILE showed variable mucin presence and p40-positive squamous differentiation suggesting phenotypic diversity in cervical precancerous lesions infected by single HPV.
Cervical cancer is a prevalent chronic malignant tumor in gynecology, necessitating high-quality images of cervical precancerous lesions to enhance detection rates. Addressing the challenges of low ...contrast, uneven illumination, and indistinct lesion details in such images, this paper proposes an enhancement algorithm based on retinex and histogram equalization. First, the algorithm solves the color deviation problem by modifying the quantization formula of retinex theory. Then, the contrast-limited adaptive histogram equalization algorithm is selectively conducted on blue and green channels to avoid the problem of image visual quality reduction caused by drastic darkening of local dark areas. Next, a multi-scale detail enhancement algorithm is used to further sharpen the details. Finally, the problem of noise amplification and image distortion in the process of enhancement is alleviated by dynamic weighted fusion. The experimental results confirm the effectiveness of the proposed algorithm in optimizing brightness, enhancing contrast, sharpening details, and suppressing noise in cervical precancerous lesion images. The proposed algorithm has shown superior performance compared to other traditional methods based on objective indicators such as peak signal-to-noise ratio, detail-variance–background-variance, gray square mean deviation, contrast improvement index, and enhancement quality index.
Toll-like receptor 4 (TLR4), one of the key immune system effectors, plays a main role in immune recognition of cervical cancer. Micro-RNAs are involved in regulation of multiple important genes in ...the progression of cervical cancer. A case-control study of 592 people was conducted from Yun’an County, Yunfu City, Guangdong Province, China. Cervical fall off epithelia were collected to detect human papilloma virus (HPV), followed by Thin Prep cytology test (TCT). Moreover, extraction of DNA from peripheral blood were performed for genotyping from the 296 patients and another 296 age-matched healthy control subjects. Logistic regression was used to determine the risk genotypes for susceptibility to cervical precancerous lesion, and multifactor dimensionality reduction (MDR) was further employed to preliminarily investigate the gene-environment interaction on risk of cervical precancerous lesion. Gene expression of miRNA-140 from serum was done by real-time PCR. We investigated whether target sites of TLR4 gene polytheisms (rs11536896 T>C, rs7873784 G>C) of miR-140 were associated with cervical precancerous lesion risk. The alleles C>A of SNP rs11536896 were significantly different in ASCUS in comparison of case group and control group with HPV infection. The presence of the allele C was associated with a higher risk of developing ASCUS lesion in HPV negative women (OR: 1.75, 95%CI:1.20-2.54, p = 0.003). There was statistically significant difference between the expression of miRNA 140 and the susceptibility to cervical precancerous lesion, in which there is down-regulation of the miRNA-140 in case group (T=6.73，P=0.007). Gene-environment interaction analysis by MDR software revealed an association among rs7873784 and hrHPV infection and more types of infected HPV (p < 0.0001, OR: 25.48; 95%Cl: 5.20-124.84). Collectively, these results suggested that rs11536896 and rs787378 from TLR4 gene were associated with risks of cervical precancerous lesion. Thus, this miRNA-140 and SNPs（rs11536896rs787378） of TLR4 gene could be considered as a potential molecular mechanism and biomarker for detecting and diagnosing cervical cancer in early time
According to the statistics of WHO/IARC, cervical cancer (CC) has become the fourth malignant cancer of female worldwide and it is one of the main causes of death of women in developing countries.
...Potential plasma and metabolic biomarkers for CC precancerous lesions and cervicitis were indicated by LC-MS techniques, and their underlying mechanisms and functions were analyzed.
Plasma samples were selected from healthy people (control), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), CC, and post-treatment patients. All polypeptide types and sequences were detected by LC-MS/MS and the results were normalized by using Pareto-scaling. Potential metabolic biomarkers were screened by applying MetaboAnalyst 4.0 software and XCMS software, and analysis of variance and enrichment analysis were performed. Metabolic pathway analysis and functional enrichment analysis were used to further investigate the significance and pathological mechanisms of potential biomarkers.
Compared with healthy people, 9 differentially expressed metabolites were screened, 4 of which were up-regulated and 5 were down-regulated. LSIL group screened 7 differentially expressed metabolites, 5 of which were up-regulated and 2 were down-regulated; CC group screened 12 differentially expressed metabolites were screened, of which 9 were up-regulated and 3 were down-regulated. Eight differentially expressed metabolites were screened in the IF group, of which 5 showed up-regulation and 3 showed down-regulation. In functional enrichment analysis, differential metabolism was found to be associated with addition and coagulation cascades. Among all potential biomarkers, 2-amino-3-methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg, 2-amino-3 -Methyl-1-butanol, L-carnitine, Asn Asn Gln Arg, Ala Cys Ser Trp, Soladulcidine, Ala Ile Gln Arg can be used as predictors of precancerous lesions at different stages of CC. Among all biomarkers, 6α-fluoro-11β1,17-dihydroxypren-4-ene-3,20-dione has higher expression in the CC and HSIL groups and lower expression in the treatment group.
By applying molecular markers to assess the progression of the disease, the accuracy and specificity of the diagnosis can be improved, which has certain prospects in clinical applications.
Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal ...cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.
Cervical precancerous lesions represented by cervical intraepithelial neoplasia (CIN) and cervical glandular intraepithelial neoplasia may progress to invasive cancer. The principle treatment of CIN ...is eradication of the transformation zone. However, all eradication methods are associated with some adverse events, particularly with perinatal consequences. It is therefore necessary to identify which women have CIN that has a low risk of transformation into invasive cancer. The presence of modifying factors can help to stratify CIN lesions according to their malignant potential. The evaluation of HPV genotype in particular holds great promise for defining patients at greater risk. Tailoring treatment to the individual patient is going to become a major consideration in the management of cervical precancerous lesions.
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