Adverse Pregnancy Outcomes Following Cryotherapy, Thermal Ablation and Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia Treatment: A Pilot Study among Zambian Women

Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who according to literature may be at risk of adverse pregnancy outcomes. This pilot study is part of a study investigating adverse pregnancy outcomes among women who received Cryotherapy, Thermal ablation and Loop Electrosurgical Excision Procedure compared to the untreated women in Zambia. Materials and Methods: This descriptive study analyzed records of 886 (n = 443 treated and n = 443 untreated) women aged 15 - 49 years. The women were either screened with Visual Inspection with Acetic Acid or treated for Cervical Intraepithelial neoplasia at the Adult Infectious Disease Centre between January 2010 and December 2020. Women meeting the criteria were identified using the Visual Inspection with Acetic Acid screening records and telephone interviews to obtain the adverse pregnancy outcome experienced. Data were analysed using STATA version 16 to determine the prevalence and obtain frequency distribution of outcomes of interest. Univariate and multivariable binary logistic regression estimated odds of adverse pregnancy outcomes across the three treatments. Results: The respondents were aged 15 to 49 years. Adverse pregnancy outcomes were observed to be more prevalent in the treatment group (18.5%) compared to the untreated group (5.4%). Normal pregnancy outcomes were lower in the treated (46.3%;n = 443) than the untreated (53.7%;n = 443). The treated group accounted for the majority of abortions (85.2%), prolonged labour (85.7%) and low birth weight (80%), whereas, the untreated accounted for the majority of still births (72.7%). Women treated with cryotherapy (aOR = 2.43, 95% CI = 1.32 - 4.49, p = 0.004), thermal ablation (aOR = 6.37, 95% CI = 0.99 - 41.2, p = 0.052) and Loop Electrosurgical Excision Procedure (aOR = 9.67, 95% CI = 2.17 - 43.1, p = 0.003) had two-, six- and ten-times higher odds of adverse pregnancy outcomes respectively, relative to women who required no treatment. Conclusion: Adverse pregnancy outcomes are prevalent among women who have received treatment in Zambia. The findings indicate that treating Cervical Intraepithelial Neoplasia has been linked to higher chances of experiencing abortion, delivering low birth weight babies and enduring prolonged labor that may result in a caesarean section delivery. Cervical neoplasia treatments, particularly Loop Electrosurgical Excision Procedure, are associated with significantly increased odds of adverse pregnancy outcomes. It is essential to include information about prior Cervical Intraepithelial neoplasia treatment outcomes in obstetric care.

Pregnancy and Obstetrical Outcomes Following Treatment for Cervical Intra-Epithelial Neoplasia (CIN) in Two Hospitals of a Low-Resource Country

Objective: In Cameroon, more than 80% of women suffering from cervical intraepithelial neoplasia (CIN) are within the reproductive age. This study intended to analyze the pregnancy outcomes following cervical treatment in Cameroon. Methods: This was a cohort study with two years retrospective data collection involving 82 women who underwent cervical treatment for CIN in two Cameroonian hospitals from January 2015 to December 2017. Data were collected from CIN treatment to end of pregnancy where applicable. Data analysis was done using Epi Info software version 3.5.4. Results: We collected data from 82 patients aged 27 to 48 years, with a mean age of 36.5 (SD: 5.3) years. During the study period, 33 out of 82 participants became pregnant 40.2 [29.56 - 51.66]%. The factor associated with pregnancy occurrence after treatment was age less than 35 years (Odds ratio = 4.37 [1.7 - 11.2]. From the 33 pregnancies recorded, 17 (51.5%) ended in a delivery, amongst which 15 (88.2%) were vaginal. Conclusion: Pregnancy frequency over two years following cervical treatment for CIN was relatively good, and younger women (age 35 years) were significantly more like to have conceived compared to their older counterparts. Post-treatment delivery outcomes seem to be similar to those in the general population.

Estimation of economic burden throughout course of cervical squamous intraepithelial lesion and cervical cancer in China:A nationwide multicenter cross-sectional study

Objective: Cervical squamous intraepithelial lesion(SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment.Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses(“diagnosis”, “initial treatment”,“chemoradiotherapy”, “follow-up” and “recurrence/progression/metastasis”) to estimate the total costs. The median and interquartile range(IQR) of total costs(including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated.Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL(LSIL)(n=549), high-grade SIL(HSIL)(n=803), cervical cancer stage ⅠA(n=226), ⅠB(n=610), ⅡA(n=487), ⅡB(n=282), Ⅲ(n=452) and Ⅳ(n=62). In urban areas, the estimated total costs of LSIL and HSIL were $1,637.7(IQR:$956.4-$2,669.2) and $2,467.1(IQR:$1,579.1-$3,762.3), while in rural areas the costs were $459.0(IQR:$167.7-$1,330.3) and $1,230.5(IQR:$560.6-$2,104.5), respectively. For patients with cervical cancer stage ⅠA,ⅠB, ⅡA, ⅡB, and Ⅲ-Ⅳ, the total costs were $15,034.9(IQR:$11,083.4-$21,632.4), $19,438.6(IQR:$14,060.0-$26,505.9), $22,968.8(IQR:$16,068.8-$34,615.9), $26,936.0(IQR:$18,176.6-$41,386.0) and $27,332.6(IQR:$17,538.7-$44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage.Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

Distribution of High-Risk Human Papillomavirus Genotypes among Women with Colposcopic Diagnosis of Cervical Intraepithelial Neoplasia in Bangladesh

Background: The incidence of cervical cancer is high in Bangladesh and there is a high prevalence of preinvasive lower genital tract disease among women of reproductive age. Persistent high-risk Human Papilloma Virus (HPV) infection is the main underlying cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). Objective: The aim of the study was to identify the subtypes of high-risk HPV infection among women with the colposcopic diagnosis of cervical intraepithelial neoplasia in Bangladesh. Methods: This cross-sectional observational study was conducted in the colposcopy clinic of Dhaka Medical College Hospital over a six-month period. A total of 100 participants were enrolled. Married women, between 30 - 60 years of age with colposcopically diagnosed cervical intra epithelial neoplasia were enrolled. Women with chronic illness, pregnancy, and women unable to consent were excluded from this study. After counselling, colposcopically directed punch biopsies were taken from each CIN case concurrently with high-risk HPV testing by polymerase chain reaction (PCR). Results: The mean age of the patients was 38.69 (SD ±7.76) years. CIN 1 was diagnosed in 57% of participants, while 24% had CIN II and 19% had CIN III lesions. High-risk HPV was present in 52 patients. HPV 16 was the most common identified in 28 (53.84%) and HPV 18 was the second most common with 20 (38.46%) either singly or in combination with other high-risk subtypes. The other HPV strains, HPV 31, 33, 35, 52, 56 and 58, were also detected either as mono or co-infections. Out of the 52 HPV positive cases, 29 (55.8%) had mono infection and 23 (44.2%) had co-infection with several subtypes. The highest incidence (50%) of oncogenic HPV infections was present among women aged 35 - 45 years. Risk factors associated with HPV positive cases were high parity (P 0.05), early age at marriage (P = 0.754) and early age of first child. Conclusion: This study identified a high prevalence of HPV 16 and 18 genotypes. HPV vaccination with the current 9-valent HPV vaccine, which contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Will be an effective public health measure to eradicate cervical cancer in Bangladesh.

Prevalence of HPV Infection And Cervical Intraepithelial Neoplasia And Attitudes towards HPV Vaccination among Chinese Women Aged 18-25 in Jiangsu Province

Objective：Few data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old.This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia（CIN） in women aged 18-25,as well as their knowledge of and attitudes towards HPV vaccination.Methods：A population-based cervical cancer screening study was conducted on women aged 18-25 in Jiangsu province in 2008.Participants provided socio-demographic,reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination.Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology（LBC） as well as visual inspection with acetic acid（VIA）.Women testing positive for any test were referred to colposcopy and biopsy.The gold standard for diagnosis of cervical lesions was directed or random biopsies.Results：Within the sample of 316 women,3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA.Among these young women,extra-marital sexual behavior of them（OR=2.0,95%CI：1.1-3.8） or their husbands（OR=2.6,95%：1.4-4.7） were associated with an increased risk of HPV positivity.Although overall HPV awareness was low,after a brief educational intervention,98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated.However,most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50-100 RMB,respectively.Conclusion：Our study indicates cervical disease burden is relatively high among sampled Chinese women aged 18-25.Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.

Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes incervical in traepithelial neoplasia and cervical cancer

The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.

RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia （CIN） and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus （HPV） infection. Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18 infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ （HC-Ⅱ） in normal group （25 cases）, CIN Ⅰ （48 cases）, CIN Ⅱ （56 cases）, CIN Ⅲ（54 cases）, and invasive cervical squamous-cell carcinoma （SCC, 31 cases）. Results The positive rates of cyclin G1 expression in CIN（77.85% ）and SCC cervical tissues （87. 10% ） were significantly higher than normal （ 8.00%, P 〈 0. 01 ）, and the intensities of cyclin G1 expression in CIN（40. 60% ） and SCC cervical tissues （61.51%） were significantly higher than normal （2. 72%, P 〈0.05）. The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups （P 〈 0.05 ）. There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ （Kendall＇s tau-b =0. 316, 0. 269, 0. 352, and 0. 474 in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ, and SCC, respectively, P 〈 0. 05 ）. Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.

Diagnostic and Therapeutic Cold Knife Conization for Cervical Intraepithelial Neoplasia

OBJECTIVE of using cold （CIN）. METHODS To evaluate the diagnostic and therapeutic efficacy knife conization for cervical intraepithelial neoplasia We retrospectively analyzed 186 cases with CIN diagnosed and treated in our hospital; compared the histologic diagnoses from cervical conization and from colposcopic multiple punch biopsies, and then evaluated their postoperative histologic findings and clinical outcomes. RESULTS Of the 186 cases, there was a correlation in histologic findings between cervical conization and colposcopic multiple punch biopsies in 138 cases （74.2%）, and there was no correlation in the other 48 cases （25.8%）. Incomplete excision was performed in 8 cases （4.3%）, but the failure rate was only 1.1%; the cure rate was 98.9%. Five cases with early invasive cancer were found. Eleven patients underwent subsequent hysterectomy. The main complications associated with conization were hemorrhage and cervical stenosis. Bleeding occurred in 8 （4.3%） of the patients, and cervical stenosis occurred in 3 （1.6%）. CONCLUSION Cervical intraepithelial neoplasia was diagnosed more accurately using conization than by colposcopic multiple punch biopsies. Conization can also play an important role in the treatment for CIN. If properly performed, the procedure has a low risk of complications. It can provide an accurate histologic representation of the disease process, and be curative in most cases.

Clinical Observation of rhIL-2 Combined with Zhenqi Fuzheng and BaofuKang Suppository in the Treatment of Cervical Intraepithelial Neoplasia II with HPV Infection

Objective: To investigate the clinical effects of recombinant human interleukin-2 (rhIL-2) combined with Zhenqi Fuzheng and Baofukang on cervical intraepithelial neoplasia II (CINII) combined with human papilloma virus infection. Methods: There were 593 patients diagnosed with CINII with HPV infection, including 296 in the control group and 297 in the experimental group. The control group was given only Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine. The experimental group was treated with rhIL-2 injection in addition to Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine which is treated for 3 months. After 3 months, Thinprep cytologic test (TCT), human papilloma virus (HPV) quantitative examination and colposcopy biopsy were reviewed. Results: After 3 months of treatment, the negative conversion rate and total effective rate of HPV in the control group were 58.11% and 70.95% respectively, and the negative conversion rate and total effective rate of the experimental group were 79.46% and 90.57% respectively. There was significant difference between the two groups (p = 0.000). The curative rate of cervical lesions was significantly higher in the test group than in the control group, 89.56%, 68.91%, respectively. The statistical difference between the two groups is significant (p = 0.000). Conclusion: It has an essential clinical value that HPV infection patients and cervical intraepithelial neoplasia II associated with HPV infection patients are treated by rhIL-2 combined with Zhenqifuzheng and Baofukang, which is safe, effective, non-invasive, reusable advantages. However, the long-term efficacy and side effects need to be further studied.

The Prevalence of High Grade Cervical Intraepithelial Neoplasia (CIN) in a Primary Human Papillomavirus (HPV) Cervical Screening Programme Population with HPV Positive and Cytology Negative Smear Results

High-risk HPV is found in 99.7% of cervical cancers. The causative role of HPV in cervical cancer has led to the inclusion of HPV testing as part of cervical screening. A pilot of HPV testing as primary screening was commenced in 2013 at six pilot sites in England. North Cumbria Integrated Care (NCIC) NHS Foundation Trust took part in the pilot, in which women with an HPV-positive/cytology-negative result were recalled at 12 months. Women with HPV type 16/18 found at initial screening and persisting at 12 months in spite of negative cytology were referred to Colposcopy services at 12 months. Women with smear positive for hrHPV other than 16/18 types were recalled twice at 12 and 24 months before referral to colposcopy. Persistent hrHPV positive/cytology negative smear at 12 and 24 months initiated a colposcopy referral. Objective: To assess the prevalence of high grade CIN and invasive cancer in patients referred to colposcopy services at NCIC NHS Foundation Trust with hrHPV positive/cytology negative smears. Method: The study was conducted at NCIC NHS Foundation Trust between January 2015 and December 2017. Data was collected retrospectively from the colposcopy data base (INFOFLEX). All patients with HPV positive/cytology negative smears seen in colposcopy clinic during the study period were included. Patients with high grade CIN, cervical glandular intraepithelial neoplasia (CGIN) or invasive cancer were recorded. Results: 763 women were included in the study. A total of 50 (6.6%) women had high grade CIN, CGIN or invasive cancer. 40 of these 50 women (80%) were treated by large loop excision of the transformation zone (LLETZ). Conclusion: HPV primary screening is more effective than cytology-based screening. A high grade HPV positive result with negative cytology, persisting for one year in type 16/18 and for two years in other high-risk HPV types, warrants referral for colposcopy, as 6.6% of women in this study had high grade or invasive pathology.

Clinical significance of colposcopy on screening cervical intraepithelial neoplasia in cytological negative and smooth cervices

Objective： The aim of the study was to evaluate the clinical value of the video colposcopy in screening cervical intraepithelial neoplasia （CIN） in cytological negative and smooth cervices by optically gynecological examination. Methods： The 1050 women, whose cervices had been shown smooth and cytological negative by optical examine, were examined with electronic colposcopy in gynecological clinic, and biopsy was taken when the double abnormality of aceto-white epithelium and iodine negative, and other abnormal images were shown. A retrospective analysis of these cases was performed. Re. suits： （1） The 514 samples from 458 cases, including 458 samples of abnormal tissues under colposcopy and 56 samples of polyp or polypoid tumors by optically, were examined by biopsy. Among them, 68 samples were found to be CIN, including 11 cases of CINII/CINIII; （2） The 72 of 1050 cases showed the double-abnormality of aceto-white epithelium and iodine nega- tive. Among them, 64 cases were CIN determined by biopsy. And the positive predictive value of the double-abnormality of aceto-white epithelium and iodine negative under colposcopy was 88.9%, with a false negative rate of 3.3%; （3） Among 458 women examined by biopsy, only one of 350 samples from cervical polyp tissue was CIN （0.3%）, while 67 of 164 samples from the tissues with abnormal colposcopic images were found to be CIN （40.9%）, indicating the close relation between abnormal colposcopic findings and CIN; （4） The results of age-distribution analysis showed that, in the 164 cases with abnormal features under colposcopy, the incidence of double abnormality of aceto-white epithelium and iodine negative was higher in the age of sexual activity, just the same as the age distribution feature of CIN; while single abnormality of iodine negative appeared more in the age of over 50 years. Conclusion： Abnormal features displayed by colposcopy, especially the double abnormality of aceto-white epithelium and iodine negative, has an important significance for the screening of cervical precancerous lesions such as CIN. For this purpose, colposcopy examination is necessary even for the cases of cytological negative and smooth cervices.

Pathological characteristics and immunophenotype analysis of cervical intraepithelial neoplasia

Objective To explore the clinical pathological features and immunophenotypes of cervical intraepithelial neoplasia(CIN).Methods The protein expression of p16, p53, Bcl-2, and c-erb B-2 in 59 cases of CIN, 20 cases of cervical squamous cell carcinoma, and 20 cases of normal cervical tissues were tested using immunohistochemistry staining.Results The expression rates of p16, p53, Bcl-2, and c-erb B-2 in CIN tissues were 76.3%(45/59), 28.85(17/59), 61.0%(36/59), and 40.0%(23/59), respectively. The expression rates of p16, p53, Bcl-2, and c-erb B-2 in cervical squamous cell carcinoma tissues were 60.0%(12/20), 60.0%(12/20), 75.0%(15/20), and 65.0%(13/20), respectively. The expression rates of p16, p53, Bcl-2, and c-erb B-2 in normal cervical tissues were 0.0%(0/20), 0.0%(0/20), 35.0%(7/20), 0.0%(0/20), respectively. In comparison to normal tissues, the differential expressions of p16, p53, and Bcl-2 in squamous cell carcinoma and CIN were statistically significant(P <0.001), whereas the difference between the squamous cell carcinoma and CIN was not significant(P >0.05). In comparison to normal tissues, the differential expressions of c-erb B-2 and p53 in squamous cell carcinoma and CIN were statistically significant(P >0.05). The differential expressions of Bcl-2, c-erb B-2, and p53 in CIN 3 were statistically significant in comparison to CIN 1 and CIN 2(P <0.05). Conclusion Overexpression of Bcl-2 occurs early in the development of cervical cancer, whereas p16 and c-erb B-2 overexpression are markers for cell malignancy. The expression of p53 is correlated with the development of cervical cancer.

Biomarkers Expression in Cervical Cancer and High Grade Squamous Intraepithelial Lesions

Objectives: The finding of new prognostic factors in human cervix cancer is necessary to improve present conventional treatments. The aim of the present study was to determine the expression and evaluate the prognostic value of hypoxia-inducible factor-1(HIF-1α), vascular endothelial growth factor (VEGF) and eritropoyetin receptor (EpoR) in cervix cancer stages IIA-IIB and in preinvasive high grade squamous intraepithelial lesions (HSIL) Methods: The study included 70 patients with cervix cancer, FIGO stages IIA-IIB, 28 patients with HSIL and normal cervix (n = 28). HIF-1α, VEGF and EpoR expression were analyzed in tissue samples by immunohistochemistry using commercial antibodies. Expression and overexpression of the tumor markers were quantified according to German Immunoreactive Score. Results: HIF-1α, EpoR and VEGF overexpression was detected in 30%, 37% and 51% of cancer patients respectively. Patients with HSIL showed enhanced expression only of EpoR and VEGF (39.2% and 71.4%) while VEGF was overexpressed in 21% of the specimen. No correlation was found between VEGF and EpoR with disease-free overall survival (OS), tumor recurrences or prognostic factors. Only overexpression of HIF-1 was associated with less median survival measured up to 24 months, unless it was not maintained a long time. Conclusion: Although any of the markers could be considered as independent prognostic factor for cervix cancer patients, our data showed a significant increase in their expression from the premalignant lesion up to the invasive stages of tumor progression.

The Role of IL-2, IL-4, IL-10 and IFN-γ Cytokines Expression in the Microenvironment of Cervical Intraepithelial Neoplasia

Objective: To investigate the role of IL-2, IL-4, IL-10 and IFN-γ cytokines in the microenvironment of cervical intraepithelial neoplasia. Methods: 180 patients participating were enrolled in this trial, where 50 cases are in control group, 50 cases are in low-grade squamous intraepithelial lesion (LSIL) group, 50 cases are in high-grade squamous intraepithelial lesion (HSIL) group, and 30 cases have cervical carcinoma. ELISA methods are used to detect the expression of IL-2, IL-4, IL-10 and IFN-γ in the lavage fluid, and all data is analyzed using one-way analysis of variance. Results: The expression of IL-2 and IFN-γ in cervical lavage fluid gradually decreases with the aggravation of the lesion. The expression of IL-4 and IL-10 increases by the aggravation of pathological changes. There were statistically significant differences in IL-2 level among the four groups. IFN-γ levels are significantly different between the cervical cancer group and the other groups, also between HSIL and LSIL group, and between HSIL and the control group, but no statistically significant difference was observed in IFN-γ e between LSIL and the control group. The expressions of IL-4 and IL-10 between the cervical cancer group and the other groups were significantly different, and also between HSIL and the control group. But there was no statistically significant difference between LSIL and the control group, HSIL and LSIL. Conclusion: The cytokines of IL-2, IL-4, IL-10 and IFN-γ in the microenvironment of the cervix play an important role in the occurrence and development of cervical intraepithelial neoplasia. This study may provide the evidence for diagnosis and treatment of cervical intraepithelial neoplasia.

The association between IgG1,IgG2 subclasses toward human papillomavirus 16-like particles in the serum and cervical intraepithelial neoplasia

Objective:The paper aimed to study the relationship between the expressions of immunoglobulin G(IgG) subclasses toward human papillomavirus 16-like particles(HPV16VLPs) in the serum of patients and different grades of cervical lesions.Methods:The expressions of IgG subclasses in 32 cases of human papillomavirus(HPV) infection,30 cervical intraepithelial neoplasia(CIN I),43 CIN Ⅱ-Ⅲ,and 24 hysteromyoma and chronic cervicitis were examined by ELISA.Results:The absorbance values of HPV16VLPs-IgG,IgG1 increased with the grade of CIN(P < 0.05).The IgG2 dominance(IgG2/IgG1 ratio > 1) from control group was 100%,87.50% for HPV infection group,75% for CIN I group,compared with that from CIN Ⅱ-Ⅲ patients(9.52%)(P < 0.05).The positive rates and absorbance values of HPV16VLPs-IgG,IgG1 and IgG2 from HPV16-DNA positive group were significantly higher than those from non-HPV16-DNA positive group(P < 0.05).There was a moderate correlation between the HPV16-DNA testing and detection of HPV16VLPs-IgG(r = 0.531,P < 0.05).Conclusion:An increase of the expressions of HPV16VLPs-IgG and its subclasses in the serum of the patients with cervical precancerous lesions,especially those with CIN II-III,might be associated with duration of HPV infection and severity of cervical lesions.An increase of the IgG2 dominance(IgG2/IgG1 > 1) in serum from low grade cervical lesions group and normal control group,might indicate the clearance of HPV infection and the regression of cervical lesions.

Efficacy and Tolerability of Thermocoagulation Treatment of High-Grade Cervical Intraepithelial Neoplasia

Purpose: Cervical cancer is still one of the main causes of cancer and mortality in women, especially in low- and middle-income countries, although it is a completely preventable disease through the detection and treatment of pre-cancer lesions. We evaluated the efficacy and tolerability of thermocoagulation treatment of high-grade cervical intraepithelial neoplasia (CIN 2 and 3). Methods: We evaluated 115 women with high-grade cervical intraepithelial neoplasia, 54 with CIN 2 and 61 with CIN 3, confirmed by biopsy and without previous treatment, from January 2016 to December 2018, undergoing thermocoagulation treatment at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil. Results: The mean age was 33.11 years (SD = 9.83) for CIN 2 and 35.28 years (SD = 7.97) for CIN 3 patients. Treatment efficacy was 90.8% in CIN 2 and 94.9% in CIN 3 cases. Pain was the main symptom reported at the time of treatment, occurring more frequently in the CIN 3 group (49.1% versus 27.8% in the CIN 2 group). As the more important long-term complication, there were 3 cases of pelvic inflammatory disease in CIN 2 (5.6%) and 3 in CIN 3 group (5.0%). The percentage of residual lesion was very low in both groups, 5 in CIN 2 group (9.2%) and 2 in CIN 3 group (3.4%). Conclusion: Thermocoagulation is an effective method for the treatment of cervical pre-cancer lesions (CIN 2 and CIN 3), with a low risk of adverse events and complications.

Relationship of high-risk HPV infection with MEKK3 and NF-κB expression in cervical intraepithelial neoplasia tissue

Objective:To study the relationship of high-risk human papilloma virus (HPV) infection with mitogen-activated protein kinase/extracellular signal-regulated kinase 3 (MEKK3) and nuclear factorκB (NF-κB) expression in cervical intraepithelial neoplasia tissue.Methods:125 cases of cervical biopsy specimens between May 2013 and March 2016 were collected. The cervical inflammation specimens, cervical intraepithelial neoplasia specimens and cervical cancer specimens were included in inflammation group, CIN group and malignant group respectively. HPV-DNA typing detection kits were used to determine HPV typing, immunohistochemical kits were used to determine MEKK3 and NF-κB protein expression, and fluorescent quantitative PCR kits were used to determine the mRNA expression of MEKK3, NF-κB and downstream molecules.Results: MEKK3 and NF-κB protein expression in high-risk HPV-positive cervical tissue were significantly higher than those in high-risk HPV-negative cervical tissue (P<0.05), and MEKK3, NF-κB, Bcl-2, XIAP, Bmi-1, TGF-β and Vimentin mRNA expression in high-risk type HPV-positive cervical tissue were significantly higher than those in high-risk HPV-negative cervical tissue (P<0.05);Bcl-2, XIAP, Bmi-1, TGF-β and Vimentin mRNA expression in tissue with positive MEKK3 and NF-κB expression were significantly higher than those in tissue with negative MEKK3 and NF-κB expression (P<0.05).Conclusions:High-risk HPV infection will increase the expression of proliferation genes Bcl-2, XIAP and Bmi-1 as well as invasion genes TGF-β and Vimentin in cervical intraepithelial neoplasia tissue through MEKK3/NF-κB pathway.

Distribution of high-risk human papillomavirus genotype prevalence and attribution to cervical precancerous lesions in rural North China

Objective: Precise prevention is more desired for cervical cancer due to the huge population, high prevalence of human papillomavirus(HPV) infection in China and the vision of screen-and-treat strategies in low-and middleincome countries(LMICs). Considerations of combining type-specific prevalence and attribution proportion to high-grade cervical intraepithelial neoplasia are informative to more precise and effective region-specific cervical cancer prevention and control programs. The aim of the current study was to determine the genotype distribution of HPV and attribution to cervical precancerous lesions among women from rural areas in North China.Methods: A total of 9,526 women participated in the cervical cancer screening project in rural China. The samples of women who tested positive for HPV were retested with a polymerase chain reaction(PCR)-based HPV genotyping test. The attribution proportion of specific high-risk human papillomavirus(HR-HPV) types for different grades of cervical lesions was calculated by using the type contribution weighting method.Results: A total of 22.2%(2,112/9,526) of women were HR-HPV positive and HPV52(21.7%) was the most common HR-HPV genotype, followed by HPV58(18.2%), HPV53(18.2%) and HPV16(16.2%). The top three genotypes detected in HR-HPV-positive cervical intraepithelial neoplasia(CIN)1 were HPV16(36.7%), HPV58(20.4%), HPV56(15.3%). Among CIN2+, the most frequent genotypes were HPV16(75.6%), HPV52(17.8%),HPV58(16.7%). HPV16, 56, 58, 53, 52, 59, 68, and 18 combined were attributed to 84.17% of all CIN1 lesions,and HPV16, 58, and 52 combined were attributed to 86.98% of all CIN2+ lesions.Conclusions: The prevalence of HR-HPV infection among women from rural areas in North China was high and HPV16, HPV58, HPV52 had paramount attributable fraction in CIN2+. Type-specific HPV prevalence and attribution proportion to cervical precancerous lesions should be taken into consideration in the development of vaccines and strategy for screening in this population.

Expression and Significance of SHP-2 in Human Papillomavirus Infected Cervical Cancer

This study investigated the expression and prognostic value of SHP-2 in cervical cancer caused by human papillomavirus (HPV) infection. Forty-five specimens from patients with cervical cancer (stageⅠ-Ⅲ), 32 specimens from patients with cervical intraepithelial neoplasia (CIN) (Ⅰ, Ⅱ) and 20 normal cervical samples from patients with hysteromyoma were collected in Department of Pathology for comparison. The expression levels of SHP-2 and IFN-β proteins were detected by using immunohistochemistry. The mRNA expression level of SHP-2 was detected by using quantitative real-time polymerase chain reaction (PCR). HPVs were detected by HPV GenoArray Test. The Spearman correlation was used to compare the expression level of SHP-2 in HPV infected cervical cancer vs non-HPV infected normal cervix. The level of SHP-2 protein expression in the cancer tissues (88.8%) was significantly higher than in CIN tissues (62.5%) and normal cervixes (45%) (P<0.05 and P<0.05, respectively). The SHP-2 mRNA levels in the cancer tissues were upregulated as compared with those in the normal cervixes (P<0.05). Twenty-one (46.7%) cervical cancers, 25 (78.1%) CINs and 17 (85%) normal cervixes showed IFN-β positive staining in cytoplasm. There was statistically significant difference in the expression rate of IFN-β between cervical cancer and normal cervix (χ2=8.378, P<0.05) as well as between cervical cancer and CIN (χ2=7.695, P<0.05). HPV16/18 infections could be found in normal cervixs (15%), CINs (68.7%) and cervical cancers (84.4%). There was a correlation between HPV infection and SHP-2 expression in cervical cancer (rs=0.653, P<0.05). SHP-2 may be a useful prognostic and diagnostic indicator for HPV infected cervical cancer. In cervical cancers, SHP-2 mRNA and protein overexpression was associated with IFN-β lower-expression.