Cervical Inflammation Research Articles

Methylation sites of human papillomavirus 16 as potential biomarkers for cervical cancer progression

ObjectiveTo investigate the methylation levels at 13 specific sites of the human papillomavirus 16 (HPV16) L1 gene as potential biomarkers for the diagnosis of cervical cancer.MethodsSamples were collected from the gynecological outpatient and inpatient departments of the Xinjiang Uygur Autonomous Region People’s Hospital. A total of 107 women participated in this study, including 54 with cervical cancer (32 Uygur, 22 Han) and 53 with cervical inflammation (32 Uygur, 21 Han). Methylation analysis was performed using pyrosequencing to quantitatively assess methylation levels at specified CpG sites within the HPV16 L1 gene.ResultsHigh methylation levels were predominantly observed at sites 5927, 5963 and 6367 in cervical cancer cells compared with inflammatory cells. Methylation patterns exhibited no significant differences between the Han and Uygur ethnic groups but correlated with viral load and age within each group. Receiver operating characteristic curve analyses of these methylation sites indicated high diagnostic accuracy in distinguishing between high-grade lesions and less severe conditions.ConclusionsMethylation of specific CpG sites in the HPV16 L1 gene holds promise as a biomarker for cervical cancer progression. The gene locus at position 6367 has important features in the methylation pattern of cervical cancer, and high accuracy shown in diagnosis make it a potential biomarker for early diagnosis of cervical cancer.

Causal Relationship Between Antibody-Mediated Immune Responses of Chlamydia trachomatis Infection and Reproductive Tract Complications: A Bidirectional Mendelian Randomization Study.

Characterized as a prevalent sexually transmitted infection, Chlamydia trachomatis is intimately associated with reproductive tract complications, including pelvic inflammatory disease (PID) and infertility. However, the causal relationships between C. trachomatis infection and reproductive tract complications remain elusive. To investigate the causal relationships between C. trachomatis antibodies and seven reproductive tract complications, we conducted a bidirectional Mendelian randomization (MR) analysis. The fundamental data were originated from the genome-wide association studies (GWAS) database. While the influences of C. trachomatis antibodies on reproductive tract complications such as tubal factor infertility (TFI) and PID have been assessed, the reverse MR analysis examined how these complications impacted C. trachomatis antibodies. The forward MR analysis revealed that the upregulation of MOMP A antibodies was significantly associated with a reduced risk of TFI (OR = 0.932, p = 0.007), while MOMP D antibodies were associated with a reduced risk of ectopic pregnancy (EP) (OR = 0.923, p = 0.005). However, no significant causal interactions were identified for other reproductive complications. Moreover, the reverse MR analysis indicated that cervicitis was significantly correlated with lower MOMP A antibody levels (OR = 0.900, p = 0.016). This study demonstrates the protective effects of C. trachomatis antibodies, particularly MOMP A and MOMP D, against TFI and EP, respectively. It also emphasizes the potential role of cervical inflammation in shaping immune responses to C. trachomatis. These insights provide a foundation for future research to develop immune-targeted therapies and integrated approaches for preventing and managing C. trachomatis-related reproductive tract complications.

Do Human Papilloma Virus and Cytological Testing Results Before Colposcopy Alter the Pathological Grading of Colposcopy Acetic Acid Visual Examination?: A Retrospective Study.

To understand whether human papillomavirus (HPV) and cytological testing (TCT [ie, "thinprep" cytological testing]) results can provide more information beyond visual information for vaginal colposcopy examinations to upgrade or downgrade the visual diagnosis of vaginal colposcopy. Data from 519 patients, who underwent vaginal colposcopy at the Beijing Obstetrics and Gynecology Hospital (Beijing, China) between January and June 2020, were included. Preoperative HPV and TCT results were statistically analyzed, and were divided into 3 groups according to postoperative cervical tissue pathological diagnosis: negative; low-grade squamous intraepithelial (LSIL); and high-grade squamous intraepithelial lesion (HSIL). Positive and negative predictive values for cervical inflammation, LSIL, and HSIL in patients diagnosed using vaginal colposcopy, based on cervical pathological grouping, and differences in HPV and TCT results among patients who underwent vaginal colposcopy, were analyzed. The age of patients diagnosed with cervicitis, LSIL, and HSIL using colposcopy gradually decreased, and the proportion of HPV16/18 infection in the HSIL group was significantly higher than the other 2 groups. There were significant differences in TCT results among the groups. According to pathological results from cervical tissue specimens, among all groups diagnosed using colposcopy, the age of the HSIL group was significantly younger than that of the other groups, and the proportion of patients with a TCT greater than LSIL was significantly higher than that of the other groups. HPV did not provide additional information for vaginal colposcopy. Young(er) patients and those with a TCT greater than LSIL may consider upgrading the vaginal colposcopy diagnosis based on imaging information.

8314 Masculinizing Hormone Therapy and Gynecological Neoplasm: a Single Institution Cohort

Abstract Disclosure: S. Korpaisarn: None. T. Ngaothepphurktharam: None. Y. Tingthanatikul: None. Background: Gynecological neoplasm/malignancy is one of the concerned areas among transgender men on masculinizing hormone therapy (MHT). Long-term MHT and gynecological neoplasm/malignancy remain unclear. Methods: A retrospective cohort chart review was done on all transgender men (TM) who underwent hysterectomy with or without oophorectomy between January 2014 and October 2022. Intraoperative findings and pathological results of genital organs, including the cervix, endometrium, myometrium, and fallopian tubes, were extracted. The pathological results were classified as benign, precancerous, and malignant. Descriptive statistical analysis was used to demonstrate the prevalence of gynecological neoplasm and malignancy. Results: A total of 30 TM underwent hysterectomy with oophorectomy. Twenty-eight (93%) had bilateral oophorectomy, and 7% had unilateral oophorectomy due to gynecological conditions. The mean age when TM underwent surgery was 32.1 ± 5.1 years, and the mean age of gender-affirming hormone initiation was 28.7± 5.1 years. The median duration of MHT before gynecological surgery was 32 months (IQR 22-59). Most TM (73%) used testosterone enanthate, 17% testosterone undecanoate, and 2 transgender men did not start MHT before genital surgery. All TM who used GHT became amenorrheic before surgery. The median preoperative testosterone level was 561.5 ng/dL (IQR 776-1189). Intraoperative findings revealed that most TM (86.7%) had unremarkable uterus size, and 13% showed enlarged uterus size. In the latter, all were from myoma uteri. Most intraoperative findings of ovaries showed 93% unremarkable. One TM had intraoperative polycystic ovarian morphology, and one showed a unilateral ovarian cyst. Cervical pathological reports showed unremarkable results in 67%. Five TM (17%) had chronic cervical inflammation. There was 1 TM (3%) who showed low-grade squamous intraepithelial lesion (LSIL) with squamous metaplasia. Regarding endometrial pathology, the mean endometrial thickness was 0.13 ± 0.08 cm. Most endometrial reports (66%) were in a proliferative phase, 27% were in an atrophic or inactive endometrium, and 7% were in the secretory phase. Regarding pathological reports of ovaries, 80% had cystic ovaries. None of the TM showed precancerous or malignant conditions of endometrium, ovaries, and fallopian tubes. PAP smear was available in 27 TM; all were negative for intraepithelial lesions or malignancy. Conclusion: Among a cohort of TM who received MHT for 32 months, there is no evidence of precancerous or malignant pathology of the endometrium, ovaries, and fallopian tubes. Most of them had thin endometrium with cystic ovaries. One TM showed LSIL with squamous metaplasia of the cervix. Healthcare providers should follow local gynecological cancer screening guidelines developed for cisgender women in their clinical practice. Presentation: 6/2/2024

Local inflammatory factors in pregnant women with various methods of cervical insufficiency treatment

the reasons for the formation of cervical insufficiency are considred to be different from violation of the ratio of connective tissue elements due to its genetic characteristics to hormonal imbalance, and the predominance of pro-inflammatory factors of the immune system. A special attention is devoted to clinical situations, when cervical insufficiency was diagnosed in terms 22-24 weeks, the treatment means an alternative between emergency cerclage and obstetric pessary. The gaol of study – to compare dynamic of vaginal microbiota and local cervical immune factors by use of different cervical insufficiency treatment methods. Materials and methods. 81 pregnant with cervical insufficiency, diagnosed in term 22-24 weeks were observed, 47 pregnant treated by cerclage procedure (group A), and 34 were fitted with an obstetric pessary (group B). 30 healthy pregnant women in the period of 22 weeks formed group C. In all patients before treatment and every two weeks after it microscopy of vaginal discharges according to Hay/Ison criteria and evaluation of cervical cytokines were performed. Results. The balance by obstetric pessary use of type I and type III by Hay-Ison criteria being similar before treatment with pregnancy prolongation is changing dramatically to the prevalence of bacterial vaginosis be use of obstetric pessary – from 30,3% and 21,2% in 2 weeks to 25,0% and 41,7% in 6 weeks, by cerclage – from 43,5% and 14,9% in 2 weeks to 30,3% and 17,5% in 6 weeks. Patients with cervical insufficiency have increased concentration of IL-6 and IL-10, but by use of obstetrical pessary additionally growth of IL-8 from 42,3 pg/ml in 2 weeks to 187,6 pg/ml in 6 weeks is registered as well as decreasing of SLPI from 1,5 μg/ml to 0,6 μg/ml. Both changes show progression of inflammation and are associated with worth pregnancy outcomes. In the same time, cerclage is assocated with growth of SLPI from 1,9 μg/ml to 4,3 μμg/ml, what is a marker of adequate immune reaction by pregnancy. There is a difference between the groups of cerclage and obstetric pessary in dynamic of microbiota changes - a tendency to increasing of laboratory criteria of bacterial vaginosis frequency in group of obstetric pessary in 2 weeks becomes significant in 4 and more in 6 weeks comparing with group of cerclage. Proper to cervical insufficiency high concentration of proinflammatory IL-6 and IL-10 by use of obstetrical pessary is complicated by increasing of IL-8 and decreasing of SLPI, what means an activation of cervical inflammation, by cerclage – a increasing of SLPI is observed, what is favourable for pregnancy.

Activation of the G Protein-Coupled Bile Acid Receptor TGR5 Modulates the HCP5/miR-139-5p/DDIT4 Axis to Antagonize Cervical Cancer Progression.

A growing body of evidence indicates that the G protein-coupled bile acid receptor, TGR5, plays a critical role in multiple physiological processes ranging from metabolic disorders to cancers. However, the biological functions of TGR5 in cervical cancer (CC) have not been elucidated. Here, using TGR5 knockout mice, we found that a deficiency of TGR5 leads to greater sensitivity to the progression of cervical inflammation. Activation of TGR5 by its specific ligands significantly attenuated the malignant behavior of CC cells. In addition, we found that TGR5 can negatively modulate the expression of lncRNA HCP5 by blocking its transcription activation when mediated by p65. HCP5 was highly expressed in CC tissues, which was positively correlated with the poor prognosis of CC patients. HCP5 knockdown notably restrained CC cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth in vivo. Furthermore, HCP5 can function as the molecular sponge for miR-139-5p to upregulate DNA damage-induced transcript 4 (DDIT4) in CC cells. Murine xenograft studies demonstrated that TGR5 suppressed the tumor formation of CC cells and downregulated HCP5 and DDIT4 while increasing miR-139-5p in the xenografts. Taken together, these findings, for the first time, indicate that TGR5 inhibits CC progression by regulating the HCP5/miR-139-5p/DDIT4 axis, suggesting that it may represent a novel and potent target for CC treatment.

Expression patterns and distribution of aquaporin water channels in cervix as a possible mechanism for cervical patency in bitches affected by pyometra

Pyometra is a life-threatening disease, the severity of which depends on cervical patency status. This study investigated cervical inflammation status as well as the expression patterns and localization of aquaporin (AQP1, AQP2, AQP3, AQP5, and AQP9), and hormone receptors in cervical tissue that influences canine pyometra. Of the 36 animals enrolled in the study, 24 were diagnosed with pyometra and separated into two groups: open cervix pyometra and close cervix pyometra, while 12 healthy animals presented for elective ovariohysterectomies were allocated into the control group. Surgical treatment was performed for treatment of pyometra. After each operation, cervix samples were collected and analyzed for AQP and hormone receptor expression patterns determined by qPCR and protein expression by means of immunohistochemistry. Blood samples were also collected to determine serum progesterone concentrations. AQP9 expression was downregulated approximately 3-fold while and PGR expression was downregulated more than 2 fold in both pyometra groups compared to the control group. AQP3 and AQP5 gene expression levels were upregulated more than 3 fold in the open-cervix pyometra group than the closed-cervix pyometra group (P < 0.05). This is the first study to describe the expression patterns and immunolocalization of AQPs in canine cervical tissue based on pyometra patency status and to report AQP3 and AQP5 expression in cervical tissue linked to cervical patency.

Prevalence and location of inflammatory and structural lesions in patients with rheumatoid arthritis and radiographic axial spondyloarthritis with chronic neck pain evaluated by magnetic resonance imaging

ObjectiveDefine the prevalence and location of inflammatory and structural lesions on magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA) and radiographic axial spondyloarthritis (r-axSpA) with neck pain as leading clinical symptom.MethodsPatients with diagnosis of RA and r-axSpA were consecutively included if they had chronic (> 3 months) neck pain. Clinical assessment, neck pain questionnaires and MRIs of the cervical spine (CS) were performed.Results107 patients (59 RA and 48 r-axSpA) were included. While there was no difference in the Northwick-Park-Neck-Pain-questionnaire, patients with RA reported higher neck pain compared to r-axSpA on a numeric rating scale (5.0 ± 3.6 vs. 3.0 ± 3.1; p = 0.003). Inflammatory lesions occurred predominantly in the craniocervical area in RA and in the lower CS segments in r-axSpA. Bone marrow edema (BME) was more frequent in axSpA (BME-score axSpA/RA: 0.35vs0.17; p < 0.001) while synovitis was visible in both but was more prevalent in RA (synovitis-score axSpA/RA: 0.02vs0.1; p < 0.001). BME was found in 8 (13.6%) vertebral corner vs. 9 (18.8%), in 2 (3.4%) facet joints vs. 7 (14.6%) and in 1 (1.7%) spinous processes vs. 9 (18.8%) in patients with RA/r-axSpA. In contrast, more patients with RA (30.5% vs6.3%) showed erosive osteochondrosis with endplate BME (p = 0.002).ConclusionWhile involvement of upper cervical inflammation was typically present in RA, r-axSpA patients showed more BME in lower CS segments, vertebral corners, facet joints and spinous processes. Neck pain is linked to upper and lower inflammatory and structural lesions of the CS in both diseases.

CO2 Cryotherapy Combined with Kushen Gel for the Treatment of Chronic Cervicitis: A Real-World Study

Background: This real-world study aims to investigate clinical efficacy and safety of CO2 cryotherapy combined with Kushen gel for chronic cervicitis. Methods: From June 2021 to December 2021, a total of 363 patients with chronic cervicitis treated in the Center for Diagnosis and Treatment of Cervical Diseases were selected. A total of 208 patients were treated with CO2 cryotherapy combined with Kushen gel, while 155 cases only received cervical CO2 cryotherapy. Results: The total effective rate of combined therapy for chronic cervicitis was 100%, with a higher cure rate than CO2 cryotherapy alone (p = 0.004), and it was significantly correlated with the degree of cervical inflammation (p &lt;0.050). Cure rate increased with decreasing severity of inflammatory response. Conclusions: CO2 cryotherapy combined with Kushen gel for chronic cervicitis has definite clinical efficacy with few adverse reactions and the combined treatment of CO2 cryotherapy with Kushen gel could enhance the therapeutic effect.

Urogenital cultures and preterm birth in women with cervical cerclage: a single center retrospective cohort study

BackgroundThe leading hypothesis of the pathogenesis of cervical insufficiency suggests a role of cervical inflammation. Urogenital tract infections could play a causative role in this process. To test this hypothesis in women with a cervical cerclage, we aimed to retrospectively examine the relationship between gestational age (GA) at delivery and positive urogenital cultures.MethodsThis single center retrospective study reviewed the records of all women with a singleton pregnancy that underwent cervical cerclage (n = 203) between 2010 and 2020 at the University Hospital of Leuven, Belgium. Transvaginal cerclages were categorized as history indicated (TVC I, n = 94), ultrasound indicated (TVC II, n = 79) and clinically indicated (TVC III, n = 20). Additionally, ten women received transabdominal cerclage (TAC). Urogenital cultures (vaginal and urine) were taken before and after cerclage with 4-week intervals. Urogenital cultures were reported ‘positive’ if urine and/or vaginal cultures showed significant growth of a microorganism. Treatment decision depended on culture growth and clinical presentation. The primary aim was to evaluate the association between the urogenital culture results and the GA at delivery, for each of the cerclage groups. Secondarily, to investigate the effect of antibiotic treatment of positive cultures on GA at delivery.ResultsPositive pre-cerclage urogenital cultures were associated with lower GA at delivery in TVC III (positive culture 26w4d ± 40d vs. negative 29w6d ± 54d, p = 0.036). For TVC I, GA at delivery was longer when pre-cerclage urogenital cultures were positive (positive culture 38w0d ± 26d vs. negative 35w4d ± 42d, p = 0.035). Overall post-cerclage urogenital cultures status was not associated with a different GA at delivery. Treating patients with pre- or post-cerclage positive urogenital cultures did also not change GA at delivery.ConclusionPositive urogenital cultures taken before clinically indicated cerclage intervention may be associated with lower GA at delivery. However, there seems to be no benefit of antibiotic treatment or routine urogenital cultures during follow-up of asymptomatic women after cerclage placement.

Human umbilical cord mesenchymal stem cells derived-exosomes alleviate LPS-induced cervical inflammation and epithelial-mesenchymal transition.

Patients with chronic cervicitis are known to have an increased risk of infection with human papillomavirus (HPV), which is the primary cause of cervical cancer. Inhibition of cervical inflammation may reduce the risk of cervical cancer. This study investigated how human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) attenuated the lipopolysaccharide (LPS)-induced cervical inflammation. Human uterine squamous carcinoma (SiHa) cells were induced with LPS to construct an inflammatory model and treated with hucMSC-Ex. The expression levels of tumor necrosis factor α (TNF-α), and interleukins (IL)-1β, IL-6, IL-10 were analyzed by qRT-PCR. Western blot was used to detect the protein expression levels of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) in cells, and CCK8 was used to examine cell proliferation, so as to explore the relieving effect of hucMSC-Ex on cell inflammation. The expression of epithelial-mesenchymal transition (EMT) markers in SiHa cells was also assessed by qRT-PCR and western blot to determine the effect of hucMSC-Ex on inflammation. Moreover, clinical cervical smears were collected to detect the expression of EMT markers in clinical exfoliated cell samples by immunofluorescence. HucMSC-Ex treatment significantly reduced the expression of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6 in the LPS-induced inflammation model, while increasing the level of anti-inflammatory cytokines, including IL-10, to reduce inflammation. HucMSC-Ex increased the expression level of epithelial markers (such as E-cadherin) while it decreased the expression of interstitial markers (such as N-cadherin), suggesting it inhibits EMT. Our results support that hucMSC-Ex alleviates LPS-induced cervical inflammation, possibly by inhibition of EMT.

Analysis of HPV prevalence among individuals with reproductive tract infections in a Chinese population.

The previous research has found that human papillomavirus (HPV) infection is the main cause of cervical cancer, but it is still unclear whether HPV infection, as well as the HPV genotypes, are related to reproductive tract infections in the Chinese population. Patients who underwent HPV screening at Shandong Maternal and Child Health Hospital were selected, and the HPV infection status was analyzed among patients with cervical lesions, bacterial vaginosis, cervical inflammation, fungal vaginitis, and pelvic infections. SPSS 22 statistical analysis was used to analyze the differences in HPV infection types and rates between the control group and the experimental group. The HPV infection rate of bacterial vaginosis (χ2 = 13.4; P < .001) and fungal vaginitis (χ2 = 3.3; P < .045) are both significantly different from the control group. The single HPV infections reveals significant differences from control group in bacterial vaginosis (χ2 = 7.3; P = .004), fungal vaginitis (χ2 = 4.5; P = .023), and cervical lesions (χ2 = 58.8; P < .001). In the bacterial infection group, HPV51 (1.9%; χ2 = 6.0; P = .008) and HPV58 (4.7%; χ2 = 3.3; P = .044) showed significant differences in infection compared to the control group. In the fungal infection group, HPV39 (2.7%; χ2 = 4.7; P = .032) showed a significant difference in infection compared to the control group. Cervical lesions, bacterial vaginosis, fungal vaginitis, and cervical lesions among Chinese population exhibit age-specified distribution. HPV infection rate in bacterial vaginitis, fungal vaginitis and cervical lesions was higher than that in normal group. HPV52 and HPV16 infection are different, and HPV39 is different between bacterial vaginitis and fungal vaginitis.

Cervical ulcer caused by group B streptococcus with bacterial vaginosis: a case report

The female genital ulcer is a manifestation of many diseases, which may vary depending on the etiology, disease duration, age, and host immunity. A middle-aged (40–50 years) woman had a 4-month history of vaginal bleeding. The results of syphilis, herpes, the cervical cancer, tuberculosis, and fungi or acute cervical inflammation caused by Chlamydia trachomatis and Mycoplasma hominis were negative through the blood test and the biopsy. Cervical discharge culture revealed positive for group B Streptococcus and bacterial vaginosis. The patient was treated with oral antibiotics for 7 days. One month later, repeat colposcopy revealed a smooth cervix and complete ulcer disappearance, while cervical discharge culture retested no group B Streptococcus and bacterial vaginosis. The patient was diagnosed with cervical ulcer. Complete medical history taking and bacterial culture of cervical discharge are important for identifying the etiology of the cervical ulcer and deciding the appropriate treatment for the disease.

Exploring Plasma-Level Gut Microbiota Mediators and Pro-Inflammatory Markers in Pregnant Women with Short Cervix and Gestational Diabetes Mellitus.

The composition of the gut microbiota (GM) undergoes significant changes during pregnancy, influenced by metabolic status, energy homeostasis, fat storage, and hormonal and immunological modifications. Moreover, dysbiosis during pregnancy has been associated with preterm birth, which is influenced by factors such as cervical shortening, infection, inflammation, and oxidative stress. However, dysbiosis also affects the levels of lipopolysaccharide-binding protein (LBP), short-chain fatty acids (SCFAs), and free fatty acids (FFA) in other tissues and the bloodstream. In this study, we investigated the plasmatic levels of some pro-inflammatory cytokines, such as matrix metalloproteinases-8 (MMP-8), interleukin-8 (IL-8), heat shock protein 70 (Hsp70), and microbial markers in pregnant women with a short cervix (≤25 mm) compared to those with normal cervical length (>25 mm). We examined the differences in the concentration of these markers between the two groups, also assessing the impact of gestational diabetes mellitus. Understanding the relationship between GM dysbiosis, inflammatory mediators, and cervical changes during pregnancy may contribute to the identification of potential biomarkers and therapeutic targets for the prevention and management of adverse pregnancy outcomes, including preterm birth.

Nuclear proinflammatory cytokine S100A9 enhances expression of human papillomavirus oncogenes via transcription factor TEAD1.

Transcription of the human papillomavirus (HPV) oncogenes, E6 and E7, is regulated by the long control region (LCR) of the viral genome. Although various transcription factors have been reported to bind to the LCR, little is known about the transcriptional cofactors that modulate HPV oncogene expression in association with these transcription factors. Here, we performed in vitro DNA-pulldown purification of nuclear proteins in cervical cancer cells, followed by proteomic analyses to identify transcriptional cofactors that bind to the HPV16 LCR via the transcription factor TEAD1. We detected the proinflammatory cytokine S100A9 that localized to the nucleus of cervical cancer cells and associated with the LCR via direct interaction with TEAD1. Nuclear S100A9 levels and its association with the LCR were increased in cervical cancer cells by treatment with a proinflammatory phorbol ester. Knockdown of S100A9 decreased HPV oncogene expression and reduced the growth of cervical cancer cells and their susceptibility to cisplatin, whereas forced nuclear expression of S100A9 using nuclear localization signals exerted opposite effects. Thus, we conclude that nuclear S100A9 binds to the HPV LCR via TEAD1 and enhances viral oncogene expression by acting as a transcriptional coactivator. IMPORTANCE Human papillomavirus (HPV) infection is the primary cause of cervical cancer, and the viral oncogenes E6 and E7 play crucial roles in carcinogenesis. Although cervical inflammation contributes to the development of cervical cancer, the molecular mechanisms underlying the role of these inflammatory responses in HPV carcinogenesis are not fully understood. Our study shows that S100A9, a proinflammatory cytokine, is induced in the nucleus of cervical cancer cells by inflammatory stimuli, and it enhances HPV oncogene expression by acting as a transcriptional coactivator of TEAD1. These findings provide new molecular insights into the relationship between inflammation and viral carcinogenesis.

C1-C2 subluxation in enthesitis-related arthritis: two case reports and literature review of ten cases

BackgroundC1-C2 subluxation is a rare complication of enthesitis-related arthritis (ERA). If left untreated, it may lead to functional impairment or cervical spinal cord compression. This study aims to highlight key points regarding the management of C1-C2 subluxation in ERA.Case presentationWe present two cases of C1-C2 subluxation: an 8-year-old boy with ERA and 16-year-old boy with ERA with bilateral sacroiliitis. Ten cases of ERA in the literature were reviewed. The diagnosis of C1-C2 subluxation is mostly based on radiographs and cervical spine computed tomography. All patients were treated with non-steroidal anti-inflammatory drugs. Six ERA patients were treated surgically for cervical fusion. Most ERA patients with sacroiliitis had cervical collar protection. Neurologic abnormalities after treatment were not reported. Despite the use of cervical collar, cervical fusion and persisting ankylosis were found in two ERA patients with sacroiliitis without surgical treatment.ConclusionsCervical spine protection and ruling out spinal cord compression should be prioritized, in addition to controlling the underlying inflammation in ERA. Cervical halter traction may be applied after severe cervical inflammation is excluded. To reduce the risk of complications, early recognition and appropriate treatments of C1-C2 subluxation in ERA are essential.

Pap smear changes and cervical inflammation in women with infertility in correlation to clinical and microbiological findings

Abstract Introduction: One of the prime causes of infertility is reproductive tract infections as they can produce marked cervical inflammation. These can be seen in Pap smears at various stages as cervical health plays an imperative role in blocking ascending infections. This study assesses infections and related changes in Pap smears from women with infertility and its association with clinical and microbiological findings. Materials and Methods: A prospective observational study was done for 3.5 years. Pap smears of women with infertility were taken, and those showing significant inflammation (&gt;50%) were studied. Relevant history and “per-speculum” findings were noted. Pap smear changes, infections or intraepithelial changes, and lactobacilli were studied. High vaginal swab culture was done, and follow-up conception data were correlated. Results: Almost 50% of women with inflammatory smears showed the presence of an infection; of which the most common was candidiasis followed by bacterial vaginosis. Out of the 12 women whose culture reports were available, 11 showed growth (90%). Most women showed depleted lactobacilli. On follow-up, the conception rate despite assisted reproductive technology was significantly lower in women with Pap smear changes (P = 0.0002). Conclusion: These observations show a strong and significant association between inflammatory Pap smears, infections in the reproductive tract, depleted lactobacilli, and conception. It is advisable that a Pap smear should be done in all cases of infertility to look for infections and inflammation, and a follow-up with high vaginal swab culture should be done in cases where inflammation is detected in a Pap smear. The following core competencies are addressed in this article: Patient care and procedural skills, Medical knowledge, Practice-based learning and improvement.

Osmotic blood-brain barrier disruption with mannitol followed by methotrexate, rituximab, and carboplatin in treating patients with newly diagnosed primary central nervous system lymphoma.

2077 Background: Osmotic blood-brain barrier disruption (BBBD) uses intra-arterial (IA) mannitol to open the neuro-vascular unit to enhance delivery of therapeutic agents to the brain. We report the results of a multi-institutional, single arm, phase 2 study evaluating the efficacy and safety of BBBD-enhanced chemotherapy in combination with immunotherapy in patients with newly diagnosed primary central nervous system lymphoma (PCNSL). PCNSL is a rare non-Hodgkin’s lymphoma that is limited to the brain, cerebrospinal fluid, spinal cord and/or the vitreoretinal compartment. Methods: Non-immunocompromised subjects with newly diagnosed PCNSL received rituximab IV over 5 hours on day 1. On days 2 and 3, under general anesthesia in the angiography suite, subjects received IA mannitol immediately followed by IA methotrexate over 10 minutes, and then IA carboplatin over 10 minutes. Subjects received sodium thiosulfate IV for hearing protection at 4 and 8 hours after each carboplatin dose. Treatment was repeated every month for up to 12 courses in the absence of disease progression or unacceptable toxicity. Per institutional recommendations, further accrual was terminated during the COVID-19 pandemic. Contrast MRI was used for response assessment based on IPCG criteria. Results: Twenty subjects (10 F, 10 M, Median KPS = 80; range 40-100) received a median of 8 cycles at 3 US institutions. Sixteen radiographic complete responses (80%) and 1 partial response were documented, 3 subjects were not evaluable (2 withdrew consent and 1 unrelated death). Median PFS was 55.2 months (95% CI :10.3 – not reached) and Median Overall survival was 82.8 months (95% CI :19.8-145.8). Fourteen patients (82% of evaluable patients) had grade 3 or 4 adverse events (AE). Grade 4 AEs (n = 14 in n = 7 patients) included neurologic toxicities (ischemia, cervical cord inflammation, neuropathy) and blood/bone marrow toxicities (lymphopenia, neutropenia, granulocytopenia). There were no treatment-related deaths. Conclusions: We demonstrate the feasibility of performing BBBD in a multi-institutional setting with excellent PFS and OS in patients without whole brain radiation or autologous transplant. Our CR rates, PFS and OS are comparable to other IV high-dose MTX regimens, with acceptable toxicity profile and no documented treatment-related deaths. Clinical trial information: NCT00293475 .

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.

Piperine Reduces Neoplastic Progression in Cervical Cancer Cells by Downregulating the Cyclooxygenase 2 Pathway.

Cervical cancer is the fourth-most common type of cancer in the world that causes death in women. It is mainly caused by persistent infection by human papillomavirus (HPV) that triggers a chronic inflammatory process. Therefore, the use of anti-inflammatory drugs is a potential treatment option. The effects of piperine, an amino alkaloid derived from Piper nigrum, are poorly understood in cervical cancer inflammation, making it a target of research. This work aimed to investigate the antitumor effect of piperine on cervical cancer and to determine whether this effect is modulated by the cyclooxygenase 2 (PTGS2) pathway using in vitro model of cervical cancer (HeLa, SiHa, CaSki), and non-tumoral (HaCaT) cell lines. The results showed that piperine reduces in vitro parameters associated with neoplastic evolution such as proliferation, viability and migration by cell cycle arrest in the G1/G0 and G2/M phases, with subsequent induction of apoptosis. This action was modulated by downregulation of cyclooxygenase 2 (PTGS2) pathway, which in turn regulates the secretion of cytokines and the expression of mitogen-activated protein kinases (MAPKs), metalloproteinases (MMPs), and their antagonists (TIMPs). These findings indicate the phytotherapeutic potential of piperine as complementary treatment in cervical cancer.