Cervical Cancer Group Research Articles

Cultivable Microbiome Approach Applied to Cervical Cancer Exploration.

Traditional microbiological methodology is valuable and essential for microbiota composition description and microbe role assignations at different anatomical sites, including cervical and vaginal tissues; that, combined with molecular biology strategies and modern identification approaches, could give a better perspective of the microbiome under different circumstances. This pilot work aimed to describe the differences in microbiota composition in non-cancer women and women with cervical cancer through a culturomics approach combining culture techniques with Vitek mass spectrometry and 16S rDNA sequencing. To determine the possible differences, diverse statistical, diversity, and multivariate analyses were applied; the results indicated a different microbiota composition between non-cancer women and cervical cancer patients. The Firmicutes phylum dominated the non-cancer (NC) group, whereas the cervical cancer (CC) group was characterized by the predominance of Firmicutes and Proteobacteria phyla; there was a depletion of lactic acid bacteria, an increase in the diversity of anaerobes, and opportunistic and non-typical human microbiota isolates were present. In this context, we hypothesize and propose a model in which microbial composition and dynamics may be essential for maintaining the balance in the cervical microenvironment or can be pro-oncogenesis microenvironmental mediators in a process called Ying-Yang or have a protagonist/antagonist microbiota role.

Characteristics of the vaginal microbiota and vaginal metabolites in women with cervical dysplasia.

Emerging evidence suggests that the vaginal microbiota is closely associated with cervical cancer. However, little is known about the relationships among the vaginal microbiota, vaginal metabolites, and cervical lesion progression in women undergoing cervical dysplasia. In this study, to understand vaginal microbiota signatures and vaginal metabolite changes in women with cervical lesions of different grades and cancer, individuals with normal or cervical dysplasia were recruited and divided into healthy controls (HC) group, low-grade squamous intraepithelial lesions (LSIL) group, high-grade squamous intraepithelial lesions (HSIL) group, and cervical cancer (CC) group. Vaginal secretion samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics, and integrated analysis. The results demonstrated that bacterial richness and diversity were greater in the CC group than the other three groups. Additionally, Lactobacillus was found to be negatively associated with bacterial diversity and bacterial metabolic functions, which increased with the degree of cervical lesions and cancer. Metabolomic analysis revealed that distinct metabolites were enriched in these metabolite pathways, including tryptophan metabolism, retinol metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as citrate cycle (TCA cycle). Correlation analysis revealed positive associations between CC group-decreased Lactobacillus abundance and CC group-decreased metabolites. Lactobacillus iners was both negative to nadB and kynU genes, the predicted abundance of which was significantly higher in the CC group. The linear regression model showed that the combination of the vaginal microbiota and vaginal metabolites has good diagnostic performance for cervical cancer. Our results indicated a clear difference in the vaginal microbiota and vaginal metabolites of women with cervical dysplasia. Specifically altered bacteria and metabolites were closely associated with the degree of cervical lesions and cancer, indicating the potential of the vaginal microbiota and vaginal metabolites as modifiable factors and therapeutic targets for preventing cervical cancer.

Association of HLA class I and II genes with cervical cancer susceptibility in a Han Chinese population.

Cervical cancer (CC) is one of the leading causes of cancer-related death in females worldwide. Genome-wide association studies (GWASs) have identified CC-related susceptibility loci in HLA regions. To investigate the associations between HLA genes and cervical intraepithelial neoplasia (CIN) or cervical cancer (CC), six loci of HLA class I (HLA-A, -B, and -C) and II (HLA-DRB1, -DPB1, and -DQB1) were selected for genotyping, and the associations between these alleles or their haplotypes with CIN or CC risk or protection from disease were evaluated. In total, 2193 participants, including 909 healthy individuals in the control group, 769 patients with CC, and 515 patients with CIN2+ (CIN II and III), were enrolled in the current study. HLA genes were genotyped using the NGSgo Illumina MiSeq workflow, and the associations between these loci and CIN2+ or CC at the allele and haplotype levels were analyzed. The allele frequencies of HLA-A*33:03, B*58:01, C*03:02, DPB1*05:01, and DRB1*12:01 were lower in both the CC and CIN2+ groups than in the control group, whereas those of B*55:02, C*04:03, and DPB1*03:01 were higher in the CC group than in the control group. In the histologic CC type analysis, the differences in the frequencies of these alleles in squamous cell carcinoma (SCC) of the cervix and stage I CC showed a consistent trend. In the haplotype analysis, the frequency of A*33:03-C*03:02-B*58:01 was lower in the CC and CIN2+ groups than in the control group, and that of A*24:02-C*04:03-B*15:25 was higher in the CC group than in both the control and CIN2+ groups. These three different haplotype frequencies were also identified in the FIGO CC stage analysis. In addition, in human papilloma virus (HPV) genotype analyses, the frequencies of HLA-C*03:02 and DPB1*05:01 were significantly lower in the CC and CIN2+ groups than in the control group, and in SCC subgroup, the frequencies of HLA-DQB1*04:01 and DRB1*04:05 were higher in the HPV other genotype infection group than in the HPV16 infection group. In both HPV16 single infection and coinfection with other HPVs, the frequency of haplotype A*33:03-C*03:02-B*58:01 was lower in both CC and CIN2+ than in the control group, while the frequencies of A*11:01-C*14:02-B*51:01 and A*24:02-C*03:04-B*13:01 were higher in the CIN2+ than in CC and the control group. In the HPV16 and other HPV infection comparisons, the frequencies of DRB1*04:05-DQB1*04:01-DPB1*02:01 and DRB1*11:01-DQB1*03:01-DPB1*05:01 were lower in the HPV16 infection group than in the other HPV infection group. Our results suggest that the HLA class I and II genes may affect the risk of CIN and CC as well as the histologic CC types and FIGO stages of CC in the Han Chinese population. In addition, HLA genes were associated with HPV16 infection at both the allelic and haplotype levels.

Analysis of the correlation between cervical HPV infection, cervical lesions and vaginal microecology.

Vaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain. This study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions. In this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions. The vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus. The study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions.

Razvoj intraepitelnih neoplazija i invazivnog karcinoma grlića materice zbog oksidativnog stresa

Abstract: Background: Cervical cancer (CC) ranks third among all malignant diseases of the female reproductive system. CC arises through a series of pathological changes called cervical intraepithelial neoplasia (CIN). Timely diagnosis and treatment of CIN are essential in the prevention of CC. Oxidative stress (OS) presents a major risk factor in the pathogenesis of both CC and CIN. This study aimed to determine the association between OS and the pathohistological severity of cervical lesions. Materials and Methods: The research was conducted at the Clinical Center of the University of Sarajevo on 240 female respondents divided into two groups. The experimental group consisted of 200 women with changes consistent with CIN, carcinoma in situ (CIS), and CC determined by biopsy, divided into 5 subgroups (CIN 1, CIN 2, CIN 3, CIS, and CC) with 40 respondents per group. The control group (N = 40) had biopsy findings that were non-pathological. The concentration of acid thiobarbituric reactive substances (TBARS) was determined for all subjects from bioptic samples using the spectrophotometric method and according to standard laboratory practice. Results: Our results showed a significant difference in age between patients with CIN 1, CIN 2, and CIN 3 and the control group as well as when compared to patients with CC. The oldest group comprised patients with CC. Tissue TBARS levels in the CIS group were significantly higher than that of the control group (p < 0.001), CIN 1 group (p < 0.001), CIN 2 group (p < 0.001), CIN 3 group (p = 0.033), as well as CC group (p = 0.002). Likewise, tissue TBARS levels in the CIN 3 group were significantly higher than those of the control group (p = 0.023), and CIN 1 group (p = 0.024). Conclusion: Compared to healthy controls, patients with CIN and CC have increased oxidative stress. Tissue TBARS levels represent a significant differentiation marker of the clinical stage of the disease and can be a useful diagnostic tool influencing the selection of therapeutic procedures.

1H magnetic resonance spectroscopy in the differentiation between low- and high-grade cervical carcinoma: is it efficient?

To evaluate the extent to which magnetic resonance spectroscopy (MRS) lipid metabolites are accurate in predicting high-grade cervical cancer. This prospective single-centre pilot study included 20 cases with pathologically proven cervical cancer. They underwent pelvic magnetic resonance imaging (MRI) with MRS. Two radiologists, blinded to the histopathological results, with 10 years of experience in gynaecological imaging, independently analysed the MRI images and MRS curves, and a third one resolved any disagreement. Using the histopathological results as a standard test, the receiver operating characteristics (ROC) curve was utilised to calculate the optimal lipid peak (1.3 ppm) cutoff for predicting high-grade cervical cancer. The difference in MRS metabolites between low- and high-grade cervical cancer groups was estimated using the Mann-Whitney test. The study included 11 high-grade and nine low-grade cervical cancer cases based on the histopathological evaluation. A lipid (1.3 ppm) peak of 29.9 was the optimal cutoff for predicting high-grade cervical cancer with 100% sensitivity, 77.8%, specificity, and 90% accuracy. Moreover, there was a significant difference between low- and high-grade cervical cancer cases concerning lipid peak at 0.9 ppm, lipid peak at 1.3 ppm, and the peak of choline with (p-value 0.025, 0.001, and 0.023), respectively. MRS might be considered a useful imaging technique for assessing the grade of cervical cancer and improving the planning of treatment. It shows a good diagnostic accuracy. Therefore, it can be adopted in clinical practice for better patient outcome.

The relationship between the expression of Stathmin and tumor immune cell infiltration in primary cervical carcinoma and its prognostic diagnostic value

To analyse the relationship between the Stathmin expression and the tumor immune cell infiltration in primary cervical carcinoma (CC), and its prognostic diagnostic value. Cervical tissue samples from 128 patients admitted to our hospital from February 2021 to February 2022 who underwent hysterectomy or cervical biopsy were selected as the observation objects, and then divided into control group (normal cervical tissue specimen, n = 30), cervical intraepithelial neoplasia (CIN) group (CIN neoplasia cervical tissue specimen, n = 30), and cervical cancer group (cervical tissue specimen of cervical cancer lesion, n = 68) according to pathological results. The expression of Stathmin was detected by Immunohistochemistry (IHC). The numbers of infiltrated neutrophils (TINs) were measured by the specific esterase staining. The pathological data of CC patients were collected, and the protein expression of Stathmin was compared with different pathological data. According to the protein expression of Stathmin, the samples were divided into Stathmin positive group and negative group. The infiltration numbers, the levels of CD3+T, CD4+T and CD8+T of TINs were compared in each group, and CD4+/CD8+ were calculated. Kaplan-Meier survival curve was used for the analysis of the relationship between the Stathmin expression and the clinical prognosis in CC. COX analysis was used to determine the factors affecting the prognosis of patients with CC. The proportion of positive expression of cervical tissue Stathmin in CIN group and cervical cancer group was significantly higher than that in the control group, and the proportion of positive expression of cervical tissue Stathmin in cervical cancer group was significantly higher than that in CIN group (P < 0.001). The ratio of the clinical stage II + III, tissue grade low and medium differentiation, and lymph node metastasis in Stathmin positive group was significantly higher than that in the Stathmin negative group (P < 0.05). Compared with the Stathmin negative group, the numbers of TINs infiltration and the level of CD4+/CD8+ were visibly higher, and the content of CD3+T, CD4+T and CD8+T were sharply lower in the Stathmin positive group (P < 0.001). Compared with the Stathmin negative group, the numbers of TINs infiltration were higher, but the content of CD4+T and CD8+T were lower in Stathmin-positive group (P < 0.001). The 68 CC patients were followed up, with a median follow-up time of 25 months (5–60 months) and an overall survival rate of 66.18 % (45/68). The results of Kaplan-Meier survival curve showed that the median survival time of patients with the Stathmin positive expression was 30 months, which was significantly lower than that of 46 months (P < 0.05) in patients with the Stathmin negative expression. Multivariate analysis of COX proportional regression risk model showed that the Stathmin positive expression, TINs infiltration numbers≥55, CD3+<5.5 %, CD4+<4.5 %, CD8+<3 %, CD4+/CD8+≥1.3 were independent factors affecting the prognosis of CC patients (P < 0.05). Stathmin in the primary tissue of CC had a significantly high expression state, which was involved in the occurrence and development of CC, thus affecting the immune microenvironment balance damaged by tumor immune cell infiltration. Detecting its expression level might help the diagnosis and prognosis assessment of CC, and Stathmin might become a new target of CC immunotherapy.

Effect of miR-138 on migration and invasion of cervical cancer cells, and the underlying mechanism

Purpose: To study the influence of microRNA-138 (miR-138) on the migration and invasion of cervical cancer cells, and the underlying mechanism.&#x0D; Methods: Fifteen cervical carcinoma subjects were enrolled in the study. Control group comprised cervical epithelial cell line (End1/E6E7) while cervical cancer group was human cervical squamous cell carcinoma cell line c33a. Both were cultured routinely without any treatment. In miR-138 overexpression group, cells were cultured in progeny of human cervical squamous carcinoma cell line c33a infected with miR-138 gene overexpression lentivirus. Expression levels of miR-138 in excised cervical cancer tissues were determined using qPCR. Cell proliferation was determined with CCK8 assay. Immunoblotting was utilized to assay protein expression levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine mRNA expression levels, while cell migration and invasion were assessed by Transwell method.&#x0D; Results: There was significant down-regulation of miR-138 expression in cervical cancer tissue, relative to nearby tissues (p &lt; 0.05). In miR-138 overexpression group, cell proliferation, number of migrated and invaded cells were significantly reduced, relative to corresponding levels in cervical cancer cells. There were significantly higher expression levels of apoptosis-related proteins FAS, Bax and FasL in miR-138 overexpression group than in cervical cancer cells, while Bcl-2 was significantly downregulated, relative to cervical cancer group (p &lt; 0.05). In cervical cancer cells, mRNA and protein levels of SIRT1 and HIF-1α were significantly up-regulated, relative to corresponding control, but levels of HIF1α and miR-138 were significantly reduced in overexpression group when compared to cervical cancer group (p &lt; 0.05).&#x0D; Conclusion: Up-regulating miR-138 in cervical cancer cells reduces HIF-1α through inhibition of SIRT1 signaling, resulting in suppression of multiplication, migration and invasion of cervical cancer cells, while enhancing apoptotic changes.

Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022

PurposeTo investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC.MethodsA total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital.ResultsThe total HPV prevalence was 74.69% (95% CI 73.28–76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53–68.77%), 80.78% (580/718, 95% CI 77.89–83.67%), 83.88% (483/576, 95% CI 80.84–86.87%), and 86.81% (408/470, 95% CI 83.74–89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89–50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50–59 years, 40–49 years, and 40–49 years, respectively.ConclusionThe prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.

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.

Contraception and sterilization selection at delivery among pregnant patients with malignancy.

Since malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long-acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery. This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long-acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics. When compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long-acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long-acting reversible contraception. Among pregnant patients aged <30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged <30 with melanoma (aOR 5.36) was also increased. The results of this nationwide assessment in the United Statessuggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type.

Analysis of somatic mutations and key driving factors of cervical cancer progression.

We investigated the somatic mutations and key driving factors of cervical cancer by whole exome sequencing . We found 22,183 somatic single nucleotide variations (SNVs) in 52 paired samples. Somatic SNVs in cervical cancer were significantly higher than those in high-grade intraepithelial lesion and low-grade squamous intraepithelial lesion groups (P < 0.05). C → T/G accounted for 44.12% of base substitution. Copy number variation (false discovery rate < 0.05) was found in 57 chromosome regions. The three regions with significant differences between cervical cancer and non-cervical cancer groups were 1q21.1, 3q26.33, and 13q33.1, covering genes related to tumor proliferation, differentiation, and apoptosis. The frequency of human papillomavirus (HPV) insertion/integration and the number of "tCw" mutations in the cervical cancer group were significantly higher than those in the non-cervical cancer group (P < 0.05). The total number of mutations was positively correlated with the number of "tCw" mutations (R 2 = 0.7967). HPV insertion/integration (OR = 2.302, CI = 1.523-3.589, P = 0.0005), APOBEC enrichment (OR = 17.875, CI = 2.117-150.937, P = 0.001), and HLA-B*39 in HLA-I (OR = 6.435, CI = 0.823-48.919, P = 0.0042) were risk factors for cervical cancer, while HLA-DQB1*05 in HLA-II was a protective factor (OR = 0.426, CI = 0.197-0.910, P = 0.032). Conclusively, HPV insertion/integration, APOBEC mutagenesis, and HLA polymorphisms are high-risk factors for cervical cancer and may be causes of genome instability and somatic mutations. This study provides experimental data for revealing the molecular mechanism of cervical cancer.

Detection of DNA Methylation in Gene Loci ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671 for Diagnosis of Cervical Cancer.

To evaluate the diagnostic value of DNA methylation detection of multiple gene loci in cervical cancer. A total of 61 cases requiring cervical biopsy were selected from the outpatient clinic of Maternal and Child Health Hospital of Hubei Province between January 2018 and December 2019. The patients were divided into four groups based on histopathologic diagnosis: cervical cancer (CC) group, high-grade squamous intraepithelial lesion (HSIL) group, low-grade squamous intraepithelial lesion (LSIL) group, and control group. HPV examination, liquid-based cytology examination, and DNA methylation detection at multiple gene sites were performed. The positive rate of DNA methylation, sensitivity, specificity, area under the curve (AUC), and other efficacy indexes were calculated to evaluate the diagnostic value of DNA methylation detection at multiple gene loci in cervical cancer. The positive rates of DNA methylation in CC, HSIL, LSIL, and control groups were 100%, 88%, 83% and 17%, respectively. The ZNF671 gene had the highest positive rate among the cervical lesion group, with rates of 57%, 76%, and 100% in LSIL, HSIL, and CC groups respectively. The combination of DNA methylation detection at multiple gene loci showed the highest diagnostic efficacy for HSIL and cervical cancer, with AUC value of 0.850 (95% CI:0.746-0.954), a Youden index of 0.654, and a sensitivity and specificity of 85% and 85.4%, respectively. The diagnostic efficacy of the combined detection was significantly higher than that of HPV examination and liquid-based cytology examination (P < 0.05). DNA methylation detection at multiple gene loci is highly effective and diagnostic tool for cervical cancer, and has potential application value in clinical practice.

Toenail arsenic species and metallome profiles associated with breast, cervical, prostate, and skin cancer prevalence in the Atlantic Partnership for Tomorrow's Health cohort.

Chronic exposure to arsenic through drinking water has been linked to several cancers. The metabolism of arsenic is thought to play a key role in arsenic-related carcinogenesis as metabolites of varying toxicity are produced and either stored in or excreted from the body. Atlantic Canada has the highest age-standardized incidence rates of all cancers in the country. This may be due to its high levels of environmental arsenic and the prevalence of unregulated private wells for water consumption. Here, we aimed to characterize the profiles of arsenic species and metallome in the toenails of four cancer groups, compare them to healthy participants (N = 338), and assess potential associations between the profiles with cancer prevalence. This study employed a case-control design. Toenail samples and questionnaire data from cases (breast, cervical, prostate, and skin cancers) and controls were sourced from the Atlantic Partnership for Tomorrow's Health (PATH) cohort study. The levels of arsenic species were measured using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) paired with High Performance Liquid Chromatography (HPLC) and total concentrations of metallome (23 metals) were determined by ICP-MS separately. Multivariate analyses were conducted to compare cases with controls within each cancer group. Arsenic speciation profiles varied by cancer type and were significantly different between cases and controls in the breast (p = 0.0330), cervical (p = 0.0228), and skin (p = 0.0228) cancer groups. In addition, the profiles of metallome (nine metals) were significantly differentiated in the prostate (p = 0.0244) and skin (p = 0.0321) cancer groups, with higher zinc concentrations among cases compared to controls. History of cancer diagnosis was associated with specific profiles of arsenic species and metallome. Our results indicate that arsenic methylation and zinc levels, as measured in toenails, may be an important biomarker for cancer prevalence. Further research is needed to use toenails as a prognostic measure of arsenic-and other metal-induced cancer.

Retrospective study of combined pelvic organ resection in the treatment of primary and recurrent pelvic malignant tumors.

e15635 Background: For locally advanced or recurrent pelvic malignancies, combined pelvic organ resection has been used to treat rectal, bladder, gynecological and other related malignancies. As an interdisciplinary and high-risk operation, the perioperative safety and future information are often very limited. We retrospectively analyzed the efficacy of PE surgery in our institution. Methods: In this retrospective study, 59 patients with pelvic malignant tumors received PE surgery from July 2015 to July 2021. They were divided into two groups according to the location of the disease: rectal tumor group (n = 40) and cervical cancer group (n = 19). The baseline data, gene detection reports, pathological reports, perioperative conditions and prognosis were analyzed. The two groups were compared by independent sample t-test; Comparison between groups χ2 test, the survival curve was drawn by Kaplan-Meier method and compared by log rank test. Results: Among these 59 patients treated with PE, the rectal tumor group and the cervical cancer group did not differ significantly in terms of demographics, operative time, hospital stay, intraoperative blood loss, and rates of use of preoperative and intraoperative radiotherapy. Compared with the two groups, the overall incidence of postoperative complications was 37% in the group with rectal tumours and 26% in the group with perineal wound infection being the most common, cervical cancer 46% and urinary tract infection being the most common. Comparing the postoperative survival OS between patients in the rectal tumor group and those in the cervical cancer group, the former was better, with 5-year overall survival rates of 37% in the rectal tumor group and 28% in the cervical cancer group. Within the group of rectal tumours, however, there are differences in survival between patients with primary (LARC) and recurrent (lrrc) rectal tumours; Patients with LARC have shown a significant survival benefit postoperatively, with 5-year overall survival rates of 40% for patients with LARC and 27% for patients with lrrc. OS was significantly better in patients with well differentiated tumors, N0 stage, and high microsatellite instability (MSI). On the basis of univariate analysis, poorly differentiated tumor, regional lymph node dissemination, MSI, and no chemotherapy received perioperatively were significant predictors of poor survival (P &lt; 0.05). Conclusions: PE is currently an effective treatment for pelvic malignancies with aggressive radical resection of lesions, which can effectively improve their cure rate, improve quality of life, and careful patient selection can optimize outcomes.

Gene expression profiling of peripheral blood mononuclear cells from women with cervical lesions reveals new markers of cancer.

Cervical cancer (CC) is a multifactorial disease of which human papillomavirus (HPV) is the main etiological agent. Despite cervical Pap smear screening and anti‑HPV vaccination, CC remains a major public health issue. Identification of specific gene expression signatures in the blood could allow better insight into the immune response of CC and could provide valuable information for the development of novel biomarkers. The present study performed a transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from Senegalese patients with CC (n=31), low‑grade cervical intraepithelial neoplasia (CIN1; n=27) and from healthy control (CTR) subjects (n=29). Individuals in the CIN1 and CTR groups exhibited similar patterns in gene expression. A total of 182 genes were revealed to be differentially expressed in patients with CC compared with individuals in the CIN1 and CTR groups. The IL1R2, IL18R1, MMP9 and FKBP5 genes were the most upregulated, whereas the T‑cell receptor α gene TRA was the most downregulated in the CC group compared with in the CIN1 and CTR groups. The pathway enrichment analysis of the differentially expressed genes revealed pathways directly and indirectly linked to inflammation. To the best of our knowledge, the present study is the first large transcriptomic study on CC performed using PBMCs from African women; the results revealed the involvement of genes and pathways related to inflammation, most notably the IL‑1 pathway, and the involvement of downregulation of the T‑cell receptor α, a key component of the immune response. Several of the stated genes have already been reported in other cancer studies as putative blood biomarkers, thus reinforcing the requirement for deeper investigation. These findings may aid in the development of innovative clinical biomarkers for CC prevention and should be further replicated in other populations.

Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status

Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.

Cervicovaginal Microbiota Profiles in Precancerous Lesions and Cervical Cancer among Ethiopian Women.

Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant dysplasia or invasive cervical cancer compared with that of healthy women. The study comprised 120 Ethiopian women (60 cervical cancer patients who had not received any treatment, 25 patients with premalignant dysplasia, and 35 healthy women). Cervicovaginal specimens were collected using either an Isohelix DNA buccal swab or an Evalyn brush, and ribosomal RNA sequencing was used to characterize the cervicovaginal microbiota. Shannon and Simpson diversity indices were used to evaluate alpha diversity. Beta diversity was examined using principal coordinate analysis of weighted UniFrac distances. Alpha diversity was significantly higher in patients with cervical cancer than in patients with dysplasia and in healthy women (p < 0.01). Beta diversity was also significantly different in cervical cancer patients compared with the other groups (weighted UniFrac Bray-Curtis, p < 0.01). Microbiota composition differed between the dysplasia and cervical cancer groups. Lactobacillus iners was particularly enriched in patients with cancer, and a high relative abundance of Lactobacillus species was identified in the dysplasia and healthy groups, whereas Porphyromonas, Prevotella, Bacteroides, and Anaerococcus species predominated in the cervical cancer group. In summary, we identified differences in cervicovaginal microbiota diversity, composition, and relative abundance between women with cervical cancer, women with dysplasia, and healthy women. Additional studies need to be carried out in Ethiopia and other regions to control for variation in sample collection.

What is the effect of vitamin D deficiency on Pap smear test results in the postmenopausal period?

This study aimed to determine the impact of vitamin D deficiency on Pap smear test results in women in the postmenopausal period. This cross-sectional study included 394 women who applied to İstanbul Medeniyet University, Göztepe Training and Research Hospital gynecology and obstetric clinic for routine Pap smear tests. This study was conducted between May 2019 and December 2020. Cases were divided into severe deficiency (&lt;12 ng/ml), moderate deficiency (12-20 ng/ml), deficiency (21-30 ng/ml), and sufficiency (&gt;30 ng/ml) according to the vitamin D levels measured in the postmenopausal period within the scope of check-up examinations. Pap smear test results compared with vitamin D levels. The mean age of the study group was 48.70±3.46 years. There was a statistically significant association between vitamin D values and Pap smear test results (p&lt;0.05). Vitamin D greater than 20 ng/ml had a significant relationship with the normal cytology results. There was a statistically significant association between vitamin D lower than 20 ng/ml and cervicitis cytology results. The results showed that the serum vitamin D and the Pap smear test results had a significant association. It is recommended that physicians prescribe the use of vitamin D supplements in women in the high-risk group of cervical cancer.

Analysis of the Efficacy of LNSRH Surgery for Early Cervical Cancer Based on T, B, and NK Lymphocytes

Background: The analysis is based on the level of T, B, NK lymphocytes to evaluate the efficacy of laparoscopic nerve-sparing radical hysterectomy (LNSRH) for early cervical cancer. Methods: Selected 30 patients with early cervical cancer who underwent LNSRH surgery in Tianjin Fifth Central Hospital from December 2019 to January 2021 as the cervical cancer group, and 30 healthy female who underwent physical examination in our hospital during the same period were selected as the control group. The expressions of CD4+, CD8+, CD20+, and CD57+ were detected by flow cytometer, female sexual function index (FSFI) and overall assessment scale of cancer treatment function (FACT-G) score were used to evaluate female sexual function and quality of life, and the receiver operating characteristic curve (ROC) was used to analyze the expression predictive value of CD4+, CD8+, CD20+, and CD57+ in LNSRH of early cervical cancer. Results: The expression of CD4+ and CD57+ in the cervical cancer group was lower than that in the healthy group,and the expression of CD8+ and CD20+ was higher than that in the healthy group (p &lt; 0.05). The expression of preoperative CD4+ and CD57+ was higher for postoperative, and the expression of preoperative CD8+ and CD20+ was lower (p &lt; 0.05) for postoperative. The expression of postoperative 1 day CD4+ and CD57+ was higher for at 3 days postoperative, and the expression of postoperative 1 day CD8+ and CD20+ was lower at 3 days postoperative (p &lt; 0.05). CD4+, CD57+ expression was positively correlated with FSFI score, and CD8+, and CD20+ expression was negatively correlated with FSFI score, CD4+, and CD57+ expression was positively correlated with FACT-G score, and CD8+, and CD20+ expression was negatively correlated with FACT-G score (p &lt; 0.05). ROC analysis of CD4+, CD8+, CD20+, CD57+ expression sensitivity was lower than the four-item combination, the specificity was higher than the four-item combination and the results with significant statistical difference (p &lt; 0.05) and the four combined tests have good predictive value for the efficacy of LNSRH for early cervical cancer (p &lt; 0.05). Conclusions: Cervical cancer patients were mainly cellular immunity and performed low expression of CD4+, high expression of CD8+, high expression of CD20+, and low expression of CD57+. T, B, and NK lymphocytes could be used for immunological detection of cervical cancer.