Cervical Cervical Intraepithelial Neoplasia Research Articles

Enhancing long-term smoking abstinence among individuals with a history of cervical intraepithelial neoplasia or cervical cancer (Project ACCESS): protocol for a randomized clinical trial

BackgroundThe prevalence of smoking among cervical cancer survivors is high and evidence-based smoking cessation interventions are critically needed. This paper describes the study design, methods, and data analysis plans for a randomized clinical trial (RCT) designed to evaluate the efficacy of a novel, personally tailored SMS-delivered text-based digital treatment adjuvant designed to enhance the long-term efficacy of a “Motivation And Problem-Solving” (MAPS) approach for smoking cessation among individuals with a history of cervical intraepithelial neoplasia (CIN) or cervical cancer. MAPS is a phone counseling approach designed to facilitate long-term abstinence that comprises 6 counseling calls over 12 months. The current trial is evaluating the efficacy of MAPS+, which comprises all MAPS components plus a 24-month digital treatment adjuvant. This trial represents a logical extension of our previous RCT, which compared the efficacy of MAPS to a quitline control condition and found that MAPS resulted in greater than a 2-fold increase in smoking abstinence at 12 months (i.e., 26.4% vs. 11.9%). This treatment effect was no longer significant at 18 months, suggesting that efficacy dissipated as time from the end of treatment increased. The primary aim of the current trial is to compare the efficacy of MAPS + and ST in facilitating long-term abstinence.MethodsIndividuals who smoke and have a history of cervical cancer or CIN (N = 340) are recruited throughout Florida and randomly assigned to Standard Treatment [ST] or MAPS+. ST participants are electronically connected with the Florida Quitline. MAPS + consists of 6 proactive MAPS-based counseling calls over 12 months plus the novel, personally tailored, text message-based treatment adjuvant delivered over 24 months. All participants receive 12 weeks of combination nicotine replacement therapy (patch and lozenge) and are followed for 24 months. Participant recruitment commenced in December 2022 and is ongoing.DiscussionThis study builds on promising results from our recent trial which found that MAPS was associated with substantially higher abstinence from smoking at the end of the 12-month treatment period. Finding that this low-burden, personally tailored digital treatment adjuvant improves the long-term efficacy of MAPS would have important clinical and public health implications.Trial registrationClinical Trials Registry NCT05645146; https://clinicaltrials.gov/ct2/show/NCT05645146; Registered on December 9, 2022.

Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis

BackgroundA higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF). MethodsWe conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology. ResultsWe included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients. ConclusionTransplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF.

FT-IR combined with PSO-CNN algorithm for rapid screening of cervical tumors

Cervical cancer is the most common gynecological malignancy.. Early and accurate identification of the stage of cervical cancer patients can greatly improve the cure rate. In this study, serum sample data were collected from patients with cervical cancer, CIN (cervical intraepithelial neoplasia) I, CIN II, CIN III and hysteromyoma using FT-IR (Fourier-transform infrared spectroscopy) technology. PSO-CNN model for early screening of cervical cancer was designed using a particle swarm algorithm to automatically build a CNN structure with variable number of layers and variable layer class parameters. The experimental results showed that PSO-CNN was the best compared with the classical Lenet, AlexNet, VGG16 and GoogLeNet deep learning models, and the accuracy of PSO-CNN in discriminating five types of samples can reach 87.2%. This study showed that FT-IR technology combined with PSO-CNN model had great potential for non-invasive, rapid and accurate identification of patients with cervical cancer, and can provide a reference for intelligent diagnosis of other diseases.

Upregulation of FOXP3+ Regulatory T Lymphocytes and CD8+ Lymphocytes in Patients with High-Grade Squamous Intraepithelial Lesions Correlated with HPV Infection

Abstract Modern therapeutic strategies for precancerous cervical intraepithelial neoplasia (CIN) focus on immune-modulatory and cancer vaccination. The local cervical immune status in cervical cancer and CIN could influence HPV infection persistence, progression and carcinogenesis. We analysed the role of FOXP3+ regulatory T lymphocytes, CD4+ and CD8+ T lymphocytes in CIN I, CIN II and CIN III patients with and without HPV infection. Sixty-two patients were enrolled in the study. Each patient underwent a colposcopy-guided cervical biopsy. FOXP3+ lymphocytes and CD4+,CD8+ lymphocytes were detected by immunostaining in tissue samples obtained from a control group (n = 10), patients with CIN I (n = 20), CIN II (n = 14) and CIN III (n = 18) lesions. HPV was assayed by Aptima. The results showed that the numbers of CD4+ T lymphocytes did not differ between patients with CIN I, CIN II, and CIN III. However, patients with CIN II and CIN III had significantly upregulated CD8+T lymphocytes compared to patients with CIN I. In addition, patients with CIN II and CIN III had increased FOXP3 + T lymphocytes compared with patients with CIN I, which was associated with HPV status. Upregulation of FOXP3+ regulatory T lymphocytes and CD8-positive lymphocytes in patients with CIN II and CIN III suggested a pivotal role of T regulatory lymphocytes and CD8+ lymphocytes for counteracting the host immune response in the progression from CIN I to CIN II and CIN III.

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

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

Costs and Resource Use Among Patients with Cervical Cancer, Cervical Intraepithelial Neoplasia, and Genital Warts in Algeria.

Background: Cervical cancer rates in North Africa have risen in the last 10 years, suggesting that this region might benefit from cervical cancer screening and HPV vaccination programs. To assess the potential benefits of cervical cancer screening and HPV vaccination in North African countries, country-specific data on the prevalence and burden of HPV-related conditions are needed.Objectives: To describe the patterns and estimate the costs of management of cervical cancer, cervical intraepithelial neoplasia (CIN), and genital warts in Algeria.Methods: This was a descriptive analysis of questionnaire data obtained from a panel of 15 oncologists, gynecologists, and dermatologists (n=5 each). Data on diagnostic and treatment patterns, recurrence, and healthcare resource use (HCRU) were obtained. The costs (in Algerian dinars) associated with diagnosis, treatment, and recurrence were estimated.Results: Diagnosis of CIN was obtained by cytology tests or lesion biopsies; for cervical cancer, lesion biopsies, MRI, and CT scans were the most common diagnostic tests. For CIN, 70% of gynecologists and/or oncologists regularly or always used conization as a treatment. Treatments used regularly or always for cervical cancer included chemotherapy (80%), hysterectomy (70%), and radiation (70%). Annual HCRU per institution included 20 outpatient visits and 15 hospitalizations for CIN, and 50 outpatient visits and 11 hospitalizations for cervical cancer. For genital warts, diagnostic tests performed regularly or always included assays for hepatitis B, hepatitis C, HIV, and syphilis; cervical cytology; and colposcopy. Cryotherapy was the universal first-line treatment. Median per-patient costs associated with diagnosis, treatment, and recurrence were 6750, 19 750, and 77 750, respectively, for CIN; 53 750, 650 000, and 431 250, respectively, for cervical cancer; and 16 075, 15 500, and 9250, respectively, for genital warts.Discussion: These results give an estimate of the HCRU and cost of cervical cancer, CIN, and genital warts and highlight the need to assess more precisely the epidemiology of these diseases in Algeria.Conclusions: This study investigated the management of patients with cervical cancer, CIN, or genital warts in Algeria and provided the first estimates of diagnosis and treatment patterns, HCRU, and costs associated with these conditions. These resource use and cost estimates highlight the need to develop prevention strategies for HPV-related pathologies.

Prevalence and Determinants of Human Papilloma Virus Infection and Cervical Intraepithelial Neoplasia (CIN) among Women Living with HIV/AIDS in Mumbai, India

AbstractHuman immunodeficiency virus (HIV) infection among women predisposes them to human papillomavirus (HPV) infection, the causative agent for cervical cancer. The study retrospectively analyzed the data of 291 women living with HIV AIDS (Acquired immunodeficiency syndrome) to assess the prevalence and determinants of the HPV infection and cervical intraepithelial neoplasia (CIN). The study found a high prevalence of cervical HPV infection (34.4%), CIN I (6.2%), and CIN II+ (8.6%). Participants with HPV DNA positivity are significantly more likely to be aged younger than 35 years (odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.01–2.69), housewives (OR = 2.29, 95% CI = 1.31–3.99), married at <20 years of age (OR = 2.02, 95% CI = 1.13–3.58), and have been pregnant more than two times (OR = 1.76, 95% CI = 1.08–2.87). Participants with CIN II+ are significantly more likely to be not married (OR = 3.363, 95% CI = 1.302–8.686). Considering the high prevalence of HPV and CIN observed among HIV women, it is worthwhile to integrate cervical cancer awareness programs and screening with routine follow-up of HIV patients at antiretroviral therapy clinic. This susceptible population needs attention to reduce the burden of cervical cancer in the country.

Vaginal drug delivery approaches for localized management of cervical cancer.

Cervical cancer or cervical intraepithelial neoplasia (CIN) remain a major public health problem among women globally. Traditional methods such as surgery are often associated with possible complications which may impact future pregnancies and childbirth especially for young female patients. Vagina with a high contact surface is a suitable route for the local and systemic delivery of drugs but its abundant mucus in continuous exchange presents a barrier for the popularization of conventional vaginal formulations including suppositories, gel, patch, creams and so on. So the development of new pharmaceutical forms based on nanotechnology became appealing owing to its several advantages such as mucosa penetration, bioadhesion, controlled drug release, and decreased adverse effects. This review provided an overview of the development of topical treatment of cervical cancer or CIN through vaginal drug delivery ranging from conventional vaginal formulations to new nanocarriers to the newly developed phototherapy and gene therapy, analyzing the problems faced by current methods used, and advising the developing trend in future. The methods of establishing preclinical animal model are also discussed.

Overexpression of LINC00673 Promotes the Proliferation of Cervical Cancer Cells.

ObjectiveTo study the expression of LINC00673 in cervical cancer and cervical intraepithelial neoplasia (CIN) and to explore the role of LINC00673 in the development of cervical cancer.MethodsThe expression of LINC00673 in serum from cervical cancer patients, CIN patients, and healthy participants was detected by RT-qPCR. The function of LINC00673 in cervical cancer cells was analyzed using in vitro and in vivo experiments.ResultsOur results revealed that serum LINC00673 levels were highest in cervical cancer patients, followed by patients with CIN and healthy controls. In vitro experiments demonstrated that overexpression of LINC00673 enhanced the proliferation and cell cycle progression of HeLa and SiHa cells. In vivo experiments showed that the tumor weight and volume of nude mice subcutaneously injected with LINC00673-overexpressing HeLa cells were larger than those of nude mice injected with control cells (P < 0.05). Western blotting showed that cell cycle-related proteins cyclin A2 and cyclin E and interstitial-associated proteins Snail and N-cadherin were upregulated and p53 signaling pathway-related proteins were downregulated in LINC00673-overexpressing HeLa and SiHa cells.ConclusionLINC00673 plays an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

Clinical presentation, treatment, and outcomes associated with vaginal intraepithelial neoplasia: A retrospective study of 118 patients.

The incidence of vaginal intraepithelial neoplasia (VAIN) is increasing annually; however, the reported values are likely underestimated. Risk factors for VAIN include advanced age, human papillomavirus (HPV) infection, history of hysterectomy, and simultaneous or previous cervical intraepithelial neoplasia (CIN) or cervical cancer cervical cancer. The most common presentation is abnormal cytology without clinical symptoms. Despite various treatment modalities available, the rate of disease recurrence is high, and its malignant potential has been documented. This study aimed to examine demographic and clinical characteristics and associated treatment outcomes of patients with VAIN. We retrospectively reviewed clinicopathologic data and clinical outcomes of patients diagnosed with VAIN at a single center between January 2010 and December 2017. Overall, 118 patients were included (average age 49.81 ± 9.77 years; range, 26-70 years). The distribution of the histologic grade was as follows: VAIN1, 30.5%; VAIN2, 41.5%; and VAIN3, 28.0%. In total, 97 (82.2%) patients had either prior or simultaneous cervical lesions, CIN (35.6%), or cervical cancer (55, 46.6%). A total of 100 cases (84.7%) were diagnosed using colposcopy and 18 (15.3%) were diagnosed by pathological accident after hysterectomy. Thin-prep cytology test (TCT) results were available for 112 (94.9%) patients, and 111 (94.1%) patients had abnormal cytology findings. Most patients were confirmed as HPV positive (115, 97.5%), and 84 (71.2%) patients were confirmed as positive for high-risk HPV types. Forty-two (35.6%) patients underwent hysterectomy before VAIN diagnosis, and the median interval between hysterectomy and VAIN diagnosis was 26.5 (range: 3-68) months. Most surgical indications were HPV-related diseases (34, 80.9%), such as CIN (8, 19.0%) or cervical cancer (26, 61.9%). Eight patients had no history of cervical lesions. A total of 100 patients underwent initial treatment. During the median follow-up period of 29 (range: 9-96) months, 78 (78%) patients experienced disease remission after initial treatment, 7 (7%) experienced disease recurrence, 10 (10%) had persistent disease, and 5 (5%) had progressive disease. Finally, two patients developed vaginal cancer without death. Colposcopy should be performed before vaginal hysterectomy for VAIN, particularly HPV-related cases. The incidence of VAIN was 20% after hysterectomy owing to non-HPV-related lesions; thus, this part of the screening should not be discontinued. VAIN grade 2,3 and VAIN associated with CIN or cervical cancer are disease types more likely to recur and progress to invasive cancer; active medical intervention is recommended.

HPV58 E7 Protein Expression Profile in Cervical Cancer and CIN with Immunohistochemistry.

Background: The persistent infection of high-risk human papillomavirus (HR-HPV) is one of the most common causes of cervical cancer worldwide, and HPV type 58 (HPV58) is the third most common HPV type in eastern Asia. The E7 oncoprotein is constitutively expressed in HPV58-associated cervical cancer cells and plays a key role during tumorigenesis. This study aimed to assess the HPV58 E7 protein expression in the tissues of cervical cancer and cervical intraepithelial neoplasia (CIN).Methods: A total of 67 HPV58-positive cervical samples were collected, including 25 cervical cancer samples and 42 CIN samples. All the tissues were examined by HPV58 E7, p16INK4a and Ki67 immunohistochemistry (IHC). At last, we analyzed their association with clinical and pathological variables.Results: HPV58 E7 expression was detected in 96% of the HPV58 DNA-positive cervical cancer tissues and 85.7% of HPV58-positive CIN tissues. 65 samples of cervical cancer and CIN tissues had p16-positive staining, while 59 samples were Ki-67 positive.Conclusions: HPV58 E7 protein is highly expressed in both cervical cancer and CIN tissues. HPV58 E7 IHC could be sensitive and specific for evaluating HPV-driven cervical cancer and pre-cancerous lesions, in combination with p16 and Ki-67 IHC.

Expression level of miRNA-210-3p in cervical cancer and its prognostic potential.

The purpose of this study was to detect the expression level of microRNA-210-3p (miRNA-210-3p) in cervical cancer (CC) tissues and its clinical significance. Expression levels of miRNA-210-3p in collected CC tissues, normal cervical tissues and cervical intraepithelial neoplasia (CIN) tissues (CIN I, CIN II, and CIN III) were tested by reverse transcriptase-polymerase chain reaction (RT-PCR). The relationship between miRNA-210-3p level and clinical data of CC patients was analyzed. Moreover, the receiver operating characteristic (ROC) was introduced for assessing the diagnostic potential of miRNA-210-3p in CC. Results revealed that miRNA-210-3p level was higher in CC tissues relative to normal cervical tissues and CIN tissues. Its expression was not correlated with age, pathological subtype, and tumor size of CC patients. However, miRNA-210-3p level was closely linked to FIGO stage, tumor differentiation, and lymphatic metastasis in CC. Based on depicted ROC, miRNA-210-3p was able to distinguish CC from normal cervical tissues and CIN tissues. MiRNA-210-3p is upregulated in CC, and its level is closely correlated with FIGO stage, tumor differentiation, and lymphatic metastasis in CC patients. Besides, miRNA-210-3p produces a pronounced diagnostic efficacy, so it can be utilized as a novel hallmark for diagnosing CC and predicting the disease progression.

Use and Utility of Endocervical Curettage at Colposcopy [21F

INTRODUCTION: Few studies have investigated the diagnostic utility of endocervical curettage (ECC) since the 2013 ASCCP Updated Consensus Guidelines. We evaluate the use of ECC at colposcopy for detection of ≥ cervical intraepithelial neoplasia (CIN) two. METHODS: IRB approved retrospective chart review included patients attending colposcopy clinic at a large urban hospital from January 2017 to January 2019 (N=402). From electronic medical records we extracted demographic characteristics, medical comorbidities, insurance status, pap smear cytology, HPV results, and colposcopy results including biopsy or ECC pathology. We used Chi-square to evaluate the use and diagnostic utility of ECC at time of colposcopy for detection of ≥ CIN two. RESULTS: An ECC was performed in 66.9% of colposcopies and 7.8% of those returned with pathology of ≥ CIN two. Transplant recipients were significantly more likely to have an ECC performed during colposcopy (X2(1, N=402)=7.23, P&lt;.05) while ECC was less frequent for those with unsatisfactory pap cytology (70% did not receive ECC, P&lt;.001). Inadequate colposcopy was associated with a higher likelihood of receiving ECC (P&lt;.0001). ECCs were significantly more likely to be performed when cervical biopsy was also performed (74% vs 58% with no biopsy; X2(2, N=402, P&lt;.05). Cervical biopsy CIN results agreed with ECC CIN results (X2(1, N=151)=20.62, P&lt;.0001). In 4.2% of colposcopies, when cervical biopsy revealed no dysplasia or CIN 1, ECC revealed ≥ CIN 2. CONCLUSION: ECCs were performed more frequently in transplant patients, inadequate colposcopy, and when cervical biopsy was also obtained. In most cases ECC did not change management.

MICA and KLRK1 genes and their impact in cervical intraepithelial neoplasia development in the southern Brazilian population

Cervical carcinoma and cervical intraepithelial neoplasia (CIN) are associated with persistent infection by oncogenic subtypes of HPV (Human Papillomavirus). Factors linked to immunity, genetics and others like oral contraceptive use, sexual behavior, coinfections with other microorganisms and smoking seem to influence the mechanisms that determine regression or progression to CIN and cervical cancer. We investigated the effect of the MHC class I chain-related gene A (MICA) and Killer Cell Lectin Like receptor K1 (KLRK1) genes on cervical cancer and CIN lesions susceptibility in a group of 195 patients from southern Brazil. There were found a significantly higher number of ex-smokers in the control group (p = 0.005). There were more oral contraceptives (OC) users in the patient group. MICA*008:01/04 allele showed a significant difference between patient and control groups (p = 0.03; OR = 0.63, 95% CI 0.41–0.96), as well as MICA*018:01(p = 0.004, OR = 0.15, 95% CI 0.03–0.64) and MICA*002:01/020 (p = 0.01; OR = 0.60, 95% CI 0.40–0.88). We also analyzed cases and controls according to the MICA-129 genotypes (Met/Val). There was found a difference (p = 0.02) with the Met/Val genotype in a higher frequency in controls and Val/Val and Val/MICA del at a higher frequency in the patient group. For the KLRK1 gene there was no significant difference between groups.

Prognostic and clinicopathological value of ZIC1 in patients with cervical squamous cell carcinoma.

The aim of the present study was to analyze the differences in zinc finger of the cerebellum 1 (ZIC1) expression between cervical cancer tissue, precancer tissue and normal cervical tissue to determine its clinicopathological and prognostic value in cervical squamous cell carcinoma (CSCC). Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of ZIC1 in 569 fresh-frozen biopsy tissues, and immunohistochemistry was performed to detect ZIC1 protein expression in 80 CSCC tissues and 320 cervical intraepithelial neoplasia (CIN) grade III samples. The association of ZIC1 expression with the clinicopathological characteristics of CSCC was then analyzed using Cox regression analysis, and Kaplan-Meier curves were used to analyze the prognostic value. The level of ZIC1 mRNA expression in CSCC was significantly lower compared with normal cervical tissues and CIN I–III tissues (P<0.001). There was a negative correlation between ZIC1 immunoreactivity score (IRS) in CSCC tissue and adjacent noncancerous tissue (R=−0.279; P=0.012); the mean IRS of ZIC1 in CSCC tissue was 5.36±3.48, which was significantly lower compared with the corresponding adjacent noncancerous tissues (11.31±5.68; P<0.001) and CIN III samples (10.42±1.54; P<0.001). In addition, expression of ZIC1 was negatively associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.027) and lymph node metastasis (P<0.001). In Cox regression analysis, ZIC1 expression [hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.40–0.92; P=0.018), FIGO staging (HR, 3.55; 95% CI, 2.35–5.37; P<0.001) and lymph node metastasis (HR, 2.50; 95% CI, 1.62–3.86; P<0.001) were three independent prognostic factors of overall survival. Furthermore, ZIC1 expression was also associated with disease-free survival (P=0.003). These results suggest that ZIC1 expression in CSCC may be lower than in normal cervical tissues or CIN tissues, and high expression of ZIC1 may be negatively associated with FIGO stage and lymph node metastasis. Therefore, ZIC1 may be a promising biomarker for the prognosis of CSCC.

Tissue-based metabolomics reveals potential biomarkers for cervical carcinoma and HPV infection.

Aberrant metabolic regulation has been observed in human cancers, but the corresponding regulation in human papillomavirus (HPV) infection-associated cervical cancer is not well understood. Here, we explored potential biomarkers for the early prediction of cervical carcinoma based on the metabolic profile of uterine cervical tissue specimens that were positive for HPV16 infection. Fifty-two fresh cervical tissues were collected from women confirmed to have cervical squamous cell carcinoma (SCC; n = 21) or cervical intraepithelial neoplasia (CIN) stages II-III (n = 20). Eleven healthy women constituted the controls (negative controls [NCs]). Real-time polymerase chain reaction (PCR) was performed to detect HPV infection in the tissues. High-resolution magic angle spinning nuclear magnetic resonance was utilized for the analysis of the metabolic profile in the tissues. The expression of rate-limiting enzymes involved in key metabolic pathways was detected by reverse-transcription quantitative PCR. An independent immunohistochemical analysis was performed using 123 cases of paraffin-embedded cervical specimens. A profile of 17 small molecular metabolites that showed differential expression in HPV16-positive cervical SCC or CIN II-III compared with HPV-negative NC group was identified. According to the profile, the levels of α- and β-glucose decreased, those of lactate and low-density lipoproteins increased, and the expression of multiple amino acids was altered. Significantly increased transcript and protein levels of glycogen synthase kinase 3 beta (GSK3β) and glutamate decarboxylase 1 (GAD1) and decreased transcript and protein levels of pyruvate kinase muscle isozyme 2 (PKM2) and carnitine palmitoyltransferase 1A (CPT1A) were observed in the patient group (p < 0.05). HPV infection and cervical carcinogenesis drive metabolic modifications that might be associated with the aberrant regulation of enzymes related to metabolic pathways.

Role of Regulatory B Cells in the Progression of Cervical Cancer

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P < 0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P < 0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r = 0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P < 0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r = ‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P < 0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

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.

PIH11 EXAMINING CERVICAL CANCER SCREENING INTERVALS AMONG WOMEN WITH NEWLY DIAGNOSED CERVICAL CANCER

To describe cervical cancer screening rates among women with newly diagnosed cervical cancer and evaluate the screening patterns against established guidelines. Women aged 21-64 years with incident cervical cancer diagnosed between 2010 and 2017 were identified in the IBM® MarketScan® Explorys® Claims-EMR Data Set, which includes detailed administrative medical and pharmacy claims data and clinical and laboratory information. The interval between cervical screening tests (cytology or cytology and HPV), rates of colposcopy and cervical intraepithelial neoplasia (CIN) were described. Women with a prior diagnosis of cervical cancer or CIN were excluded. There were 3,291 newly diagnosed cervical cancer cases. The look-back period ranged from 1 to 15 years, during which 75% of women had evidence of cervical cancer screening while 25% did not have evidence of a cervical cancer screening exam in the linked claims-EMR database. Among women with no record of a screening exam, many demonstrated a history of other medical encounters; 82% had at least one physician visit in the year prior to their cervical cancer diagnosis. Of the 3,921 women with cancer, 1,279 had at least 3 years of continuous data during the 10 years prior to the diagnosis of cervical cancer. Of these, a subgroup of 811 (84%) did not have documentation of prior CIN. Among this subgroup of women, 3.4 unique screening exams were observed with an average interval of 3.8 years. The occurrence of cervical cancer among screened women adds information regarding how to optimize a screening program to prevent the occurrence of advanced disease. The observation that most unscreened women had concurrent medical encounters underscores the opportunity for health care providers to discuss a patient’s risk, confirm the date of her last cervical screening exam and reinforce the importance of routine cervical cancer screening.

High-risk human papilloma virus infection and cervical neoplasm in female inflammatory bowel disease patients: a cross-sectional study

Background and aimThis cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus (HPV) infection, especially types 16 and 18, and cervical neoplasia in female Inflammatory bowel disease (IBD) patients.MethodsFrom July 2014 to January 2017, sexually active, female, Chinese IBD patients (21–60 years) and age-matched controls underwent cervical ThinPrep cytology testing (TCT) and high-risk HPV-DNA detection, and completed questionnaires about awareness of cervical cancer and HPV. Cervical dysplasia was categorized as cervical intraepithelial neoplasia (CIN) 1, 2 and 3.ResultsOf 124 IBD patients (30 ulcerative colitis and 94 Crohn’s disease), 17 (13.7%) had high-risk HPV among whom 9 (7.3%) had HPV 16/18 infection and 4 (3.2%) had cervical CIN (3 CIN 3, 1 CIN 1) by pathology. Among 372 controls, 33 (8.9%) had high-risk HPV and only 1 (0.3%) had HPV 16 infection. Cervical TCT detected atypical squamous cells of unknown significance in one control; no control had CIN. The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls (both P < 0.001). The HPV-infection rate was higher in patients administered methotrexate [P = 0.005, odds ratio (95% confidence interval) 4.76 (1.471–15.402)] or more than two immunosuppressants [P = 0.013, odds ratio (95% confidence interval) 3.64 (1.255–10.562)]. Thiopurine, steroid, infliximab and disease behavior/location were not associated with HPV infection. Only 29.3% of patients had undergone cervical-cancer screening. Awareness of HPV infection and HPV-related cervical cancer was poor (28.2%).ConclusionsFemale IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia, which may be associated with immunosuppressants. Education and routine follow-up with HPV-DNA testing and TCT are recommended, especially in female Chinese IBD patients.