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.

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.

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.

The Relationship between p53 Expression and Human Papillomavirus in Premalignant and Malignant Uterine Cervical Lesions

Objective: We aimed to retrospectively examine a series of premalignant and malignant cervical tissues to study a high-risk HPV 16 infection that, among cervical tissue lesions, carries the greatest risk of conversion to cancer, and the presence of p53 protein immunoreactivity, a tumor suppressor gene product. Methods: Paraffin blocks were studied via immunohistochemical (IHC) method to explore the presence of HPV 16 in 59 premalignant and malignant cervical lesions as well as immunoreactivity of the p53 oncoprotein, the most common cellular tumor suppressor gene product in human cancers. Results: In our series, mutant p53 positivity rate was 35.3% for low-grade CIL, 40% for high-grade CIL, and 46.8% for invasive carcinoma cases. Immune staining for high-risk HPV 16 type yielded a positive staining rate of 47% in low-grade CIL, 80% in high-grade CIL, and 50% in invasive carcinoma. Conclusion: The results of our study indicate a progressive increase in p53 oncoprotein reactivity from cervical intraepithelial neoplasia to invasive carcinoma. This suggests the clinical importance of p53 immunoreactivity in dysplastic progression and neoplastic transformation. HPV is the most commonly encountered oncogenic type in cervical lesions, especially in high-grade CIL and invasive carcinomas. Results of the previous reports suggest that HPV-positive carcinomas release wild type p53 and HPV-negative ones release mutant type p53 were not confirmed by our results, which indicated a mutant type p53 reactivity in HPV- 16 positive carcinoma cases.

Large pelvic mass arising from the cervical stump: A case report

BACKGROUND A large cervical cyst with a cervical high-grade squamous intraepithelial lesion arising from the cervical stump is rare.After supracervical hysterectomy,there is a risk of various lesions occurring in the cervical stump.We review the types and characteristics of cervical stump lesions and compare total hysterectomy with subtotal hysterectomy.Gynecologists should choose the most suitable surgical method based on both the patient’s condition and wishes.If the cervix is retained,patients require a close follow-up.CASE SUMMARY A 57-year-old woman was admitted to the Gynecology Department for a large pelvic mass.Her chief complaint was abdominal distention for two months.She had undergone subtotal supracervical hysterectomy for leiomyoma 14 years prior.Abdominal ultrasonography detected a 9.1 cm×8.5 cm×8.4 cm anechoic mass with silvery fluid in the pelvic cavity and high-risk human papilloma virus 53(HPV53)was positive.The admission diagnosis we first considered was a pelvic mass mimicking carcinoma of the cervical stump.We performed a laparotomy and a rapid frozen biopsy was suggestive of a fibrous cyst wall coated with a high squamous intraepithelial lesion.The pelvic mass was removed,and a bilateral adnexectomy was implemented.Final pathology confirmed that the pelvic mass was a large inflammatory cyst with a cervical high-grade squamous intraepithelial lesion.After successful intervention,the patient was discharged one week after surgery and there was no recurrence of the vaginal stump at 43 mo.CONCLUSION When addressing benign uterine diseases,gynecologists should pay adequate attention to retaining the cervix.If the cervix is retained,patients require a close follow-up.

Prevalence of Cervical Human Pappillomavirus Infection in Awka, Nigeria

Prevalence of cervical Human Papillomavirus infection and type distribution vary with different environments. Knowledge of this will help in some cervical cancer interventions such as vaccine administration. This study aimed at determining the prevalence of cervical HPV infection among women attending a tertiary hospital in Awka, Nigeria. To evaluate cervical HPV Infections, cervical samples were collected over a period of 1 year from 405 consenting women. Multiplex PCR and cytology were used in the study. Semi-structured questionnaire was used to obtain the demographic characteristics of the participants. Statistical analysis was done using IBM SPSS statistics version 21. The findings showed that of the 405 women, 387 (94.4%) had normal cytology, and 18 (4.4%) had Low-grade Squamous Intraepithelial Lesion (LSIL). There was no High-grade Squamous Intraepithelial Lesion (HSIL). HPV prevalence of (79) 19.5% was obtained overall in the 405 women, (75 of 387) 19.4% with normal cytology, (4 of 18) 22.2% with LSIL. Age specific prevalence peaked at age group 30 - 39 and a second peak at 60 - 69. HPV types obtained were HPV 16 31 (7.7%), HPV 18 24 (5.9%), HPV 35 3 (0.7%), HPV 33 9 (2.2%), HPV 68 3 (0.7%) and multiple infections (9) 2.2%. HPV 16 was the only type found in LSIL. Regular HPV typing and screening of our women for HPV infection and Pap’s smear can go a long way in the reduction of cervical cancer.

Correlative analysis between abnormal cervical cytology and pathology of vaginoscopic biopsy or conization

Objectives: To evaluate the predictive value of cervical intraepithelial neoplasia (CIN)III/ carcinoma in situ (CIS) by correlating analysis between abnormal cervical cytologic findings and pathological diagnosis of vaginoscopic biopsies or conization.Methods: Routine cervical cytology screening was performed in 31,634 cases by fluid-based thin-layer method (ThinPrep cytology test, TCT), 948 patients had both abnormal squamous cell appearance by TCT and pathological diagnosis of vaginoscopic biopsies and /or cervical conization. The predictive value of CINIII/CIS were studied retrospectively by correlating analysis of different cytology abnormalities and pathology diagnosis.Results: Cytologically, 1,260 out of 31,634 TCT tests showed abnormal squamous cells appearance, including atypical squamous cell of undetermined significance (ASCUS) 675 cases(2.13%), low squamous intraepithelial lesion (L-SIL) 379 cases(1.20%), high squamous intraepithelial lesion (H-SIL)176 cases(0.56%),cancer 30 cases (0.09%). Among 948 patients with pathological diagnosis, there were CINII-III in 70 cases(7.38%) and CINIII/CIS in 56 cases.(5.91%). The relative risks (RR) of different precancerous TCT results in predicting CIN III/CIS validated by pathology are as follow: AUSCUS 14.7% (95% confidence interval (CI) 8.0-27.0), Lsil 13.9% (95% CI 6.3-30.9), Hsil 126.1 (95% CI 60.6-218.6). The RR of AUSCUS group is not significantly different from that of L-SIL group(P =0.951). However, the RR of CINⅢ/CIS morbidity between the H-SIL or cancer group and the ASCUS or L-SIL group are significantly different (all P value <0.01).Conclusion: Vaginoscopic biopsy could verify pathological CINⅡ-Ⅲ and CINⅢ/CIS from cases with abnormal TCT results. There is significantly greater risk of being CINⅢ/CIS validated by vaginoscopic biopsy in the H-SILpatients,while ASCUS and L-SIL group have the coequal risk.

Expression and clinical significance of Klotho and Beclin1 in cervical squamous carcinoma

Objective:To detect the expression of klotho and beclin1 protein in chronic cervicitis, low grade squamous intraepithelial lesion (LSIL) group, high grade squamous intraepithelial lesion (HSIL) group and cervical squamous cell carcinoma (SCC) group.Methods:Immunohistochemical technique (Envision) was used to detect the expression of Klotho and Beclin1 proteins in each study group. The correlation between the expression of the above two proteins and the pathological features of SCC and the expression of the two proteins in SCC were analyzed.Results: The positive expression rates of Klotho protein in chronic cervicitis group, LSIL group, HSIL group and SCC group were 95%, 92.86%, 65.38%, 27.90%, respectively. The positive rates of Beclin1 protein in chronic cervicitis group, LSIL group, HSIL group were 25.0%, 28.57%, 38.46% and 74.42%, respectively. The differences were statistically significant. The expression of Klotho and Beclin1 in SCC was correlated with the degree of tumor differentiation, but not with the age, figo stage, lymph node metastasis, tumor size, depth of invasion and vessel invasion, but not with the age of the patient, tumor figo stage, lymph node metastasis, tumor size, depth of invasion and vessel invasion. There was no correlation between the expression of klotho and beclin1 in SCC tissues.Conclusion: The abnormal expression of klotho and beclin1 may be related to the development, invasion and metastasis of cervical squamous cell carcinoma.

常规器械免举宫经脐单孔腹腔镜全子宫切除术

目的探讨常规器械免举宫经脐单孔腹腔镜全子宫切除术治疗宫颈病变的应用价值。方法选择2021年12月~2023年6月因宫颈高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)或宫颈癌ⅠA1期行腹腔镜全子宫切除术60例,按患者意愿行经脐单孔腹腔镜手术及多孔腹腔镜手术各30例,均使用常规器械,不使用举宫器,比较2组手术指标。结果2组均未出现中转开腹及泌尿系、肠道或大血管等损伤。单孔组出血量较少[(54.6±20.5)ml vs.(67.5±27.0)ml,P=0.041],排气较早[(27.6±8.0)h vs.(32.2±9.0)h,P=0.040],总住院时间较短[(4.4±1.5)d vs.(5.1±1.2)d,P=0.044]。2组子宫重量、手术时间以及术后并发症差异无显著性(P>0.05)。2组切口愈合良好,未出现与穿刺器相关的近期并发症(如穿刺孔感染、出血)或远期并发症(如脐疝、切口疝)。结论免举宫经脐单孔腹腔镜全子宫切除术出血少,术后恢复快,瘢痕最小化,并发症与传统腹腔镜手术相似。

宫颈癌癌组织及外周血单个核细胞中MAGE-A3的表达及其临床意义

目的探究宫颈癌癌组织及外周血单个核细胞(PBMC)中黑色素瘤相关抗原-A3(MAGE-A3)表达及临床意义。方法通过方便抽样选取2020-05至2022-05保定市妇幼保健院及河北大学附属医院收治的因宫颈病变拟行宫颈锥切术或广泛性子宫切除术患者96例,根据术后病理结果分为宫颈癌组和子宫颈鳞状上皮内病变(SIL)组,采用免疫组化法检测病变组织MAGE-A3蛋白表达情况。采用实时荧光定量PCR法检测宫颈病变组织及PBMC中MAGE-A3 mRNA表达水平,分析宫颈癌患者癌组织及PBMC中MAGE-A3mRNA表达与血清肿瘤标志物相关性以及癌组织MAGE-A3蛋白表达与临床病理特征关系。结果宫颈癌癌组织MAGE-A3蛋白表达阳性率与FIGO分期、肿瘤的直径大小、分化程度、淋巴结转移、感染高危型HPV有关(P<0.05),与年龄、病理类型无关(P>0.05)。宫颈癌组癌组织和PBMC中MAGE-A3 mRNA表达水平分别为(1.33±0.46)、(1.70±0.49),均显著高于SIL组(0.59±0.20、0.92±0.33)(P<0.05),血清SCC-Ag[(3.87±1.69)ng/ml]、CA-125[(48.62±15.10)U/ml]均显著高于SIL组[(0.70±0.32)ng/ml、(25.36±8.33)U/ml](P<0.05);宫颈癌组癌组织MAGE-A3蛋白表达阳性率(66.07%)显著高于SIL组(30.00%)(P<0.05);宫颈癌患者癌组织、PBMC中MAGE-A3 mRNA表达水平与血清SCC-Ag、CA-125均呈正相关(P<0.05)。结论宫颈癌患者癌组织及PBMC中MAGE-A3表达均上调,且与患者血清肿瘤标志物水平及病情进展有关,MAGE-A3有望成为早期宫颈癌诊断的重要标志物。

Triage for management of cervical high-grade squamous intraepithelial lesion patients with positive margin by conization： a retrospective analysis

The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion （HSIL） patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 （47.06%） patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma （3 stage IA1 and 1 stage IA2 patients）. Univariate analysis showed that patient age 〉 35 years （P = 0.005）, menopausal period 〉 5 years （P = 0.0035）, and multiple- quadrant involvement （P=0.001） were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement （P=0.001; OR, 3.701; 95%CI, 1.496-9.154） was an independent risk factor for residua! disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider re- conization or re-assessment.

人乳头瘤病毒感染情况、阴道微环境指标与宫颈病变的相关性分析

目的探讨人乳头瘤病毒(HPV)感染情况、阴道微环境指标与宫颈病变的相关性。方法选取2022年1月至2023年4月该院收治的307例宫颈病变患者作为研究对象,按照其液基细胞学检查(TCT)和病理检查结果分为低级别上皮内瘤变(LSIL)组(169例)、高级别上皮内瘤变(HSIL)组(97例)和宫颈癌组(SCC)(41例);另选取同期该院200例TCT结果正常无宫颈病变的健康体检者作为对照组。对所有研究对象进行HPV和阴道微环境检测。采用Spearman相关对宫颈病变严重程度与年龄的相关性进行分析。结果宫颈病变严重程度与年龄呈正相关关(r=0.306,P<0.05)。HPV感染率较高的型别依次为16、52、58、53型。LSIL组、HSIL组和SCC组HPV多重感染率均高于对照组,HSIL组和SCC组均高于LSIL组,差异均有统计学意义(P<0.05);SCC组HPV多重感染率与HSIL组比较,差异无统计学意义(P>0.05)。酸碱度(pH)、过氧化氢(H 2O 2)、白细胞酯酶(LE)异常比例均为SCC组>HSIL组>LSIL组>对照组,且SCC组、HSIL组和LSIL组与对照组比较,差异均有统计学意义(P<0.05)。阴道清洁度异常比例为SCC组>HSIL组>LSIL组>对照组,LSIL组阴道清洁度异常比例与对照组比较,差异无统计学意义(P>0.05),HSIL组和SCC组阴道清洁度异常比例与对照组比较,差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,阴道pH>4.5、LE阳性、清洁度为Ⅲ°~Ⅳ°增加了宫颈病变发生的风险,H 2O 2阳性对宫颈病变的发生有抑制作用。结论HPV感染、阴道微环境指标异常改变与宫颈病变的发生和发展存在一定的相关性,可为临床预防和治疗宫颈病变提供参考依据。

部分微小RNA在宫颈癌患者血清中的表达及早期筛查的意义研究

目的探讨微小RNA(miR)-126-3p、miR-199a-3p、miR-150-5p、miR-221-3p在宫颈癌患者血清中的表达及早期筛查的意义。方法选取2020年12月至2022年12月河北省邯郸市中心医院住院治疗患者及同期于该院行体检的、宫颈癌前筛查未见明显异常的健康女性作为研究对象。根据健康状况不同分为宫颈癌组(61例)、宫颈高级别鳞状上皮内病变(HSIL)组(40例)和对照组(健康女性,40例)。比较组间以上4种miR的相对表达情况差异,分析miR相对表达水平与宫颈癌患者临床及病理指标的相关性及对宫颈癌的预测价值。结果宫颈癌组患者血清中miR-126-3p、miR-199a-3p的相对表达水平低于对照组和HSIL组,miR-150-5p、miR-221-3p的相对表达水平高于对照组和HSIL组,差异均有统计学意义[(0.31±0.06)比(0.50±0.08)、(0.38±0.08),(2.56±0.36)比(3.38±0.51)、(3.25±0.60),(2.91±0.49)比(1.42±0.49)、(2.20±0.53),(3.24±0.96)比(1.83±0.63)、(2.02±0.62)](均P<0.05)。宫颈癌组患者国际妇产科联盟分期Ⅰ期+Ⅱ期和Ⅲ期者血清miR-126-3p、miR-221-3p相对表达水平差异有统计学意义(P<0.05)。miR-126-3p联合miR-199a-3p检测预测宫颈癌的敏感度为95.0%、特异度为76.3%,miR-150-5p联合miR-221-3p检测的敏感度为91.7%、特异度为85.0%。结论miR-126-3p、miR-199a-3p、miR-150-5p、miR-221-3p在宫颈癌和癌前病变患者血清中异常表达,与宫颈癌的发生发展密切相关,对于宫颈癌诊治可能提供新的靶点。miR-150-5p联合miR-221-3p检测预测宫颈癌的敏感度及特异度均较高,可以考虑作为宫颈癌早期筛查的标志物。

宫颈锥切术对患者妊娠结局的影响及不良妊娠结局危险因素分析

背景宫颈高级别鳞状上皮内病变患者锥切术后仍有部分患者有生育需求,对于这部分患者的治疗及术后管理尚未形成临床共识。目的研究宫颈锥切术对宫颈高级别鳞状上皮内病变患者妊娠结局的影响,并分析不良妊娠结局(早产、剖宫产、低体质量出生儿)的危险因素。方法2017年9月1日—2021年12月31日在解放军总医院第一医学中心进行子宫颈锥形切除术并在术后获得活产的患者65例作为观察组,并收集同时期在解放军总医院产科住院生产的正常患者65例作为对照组,比较两组患者的一般资料(年龄、身高、体质量)和妊娠结局(是否早产、分娩方式),观察组再以锥切高度(病理结果)是否>1.5 cm进行分组,分析锥切高度与早产、剖宫产率等妊娠结局的关系,寻找锥切术后不良妊娠结局的危险因素。结果锥切术后妊娠早产率改变(P<0.05)。锥切高度>1.5 cm与≤1.5 cm的剖宫产率、早产发生率差异无统计学意义(P>0.05)。锥切高度>1.5 cm是锥切术后不良妊娠结局的独立关联因素(OR=3.868,95%CI:1.256~11.918)。结论宫颈电刀锥切术后妊娠的早产率增加,对于有生育要求的患者,在切净病灶的前提下可尽量保证锥切高度不超过1.5 cm,在手术半年后备孕,妊娠过程进行严密的监测和必要的宫颈环扎术可避免不良妊娠事件的发生。

阴道灌洗液中炎症因子与CD4^(+)和CD8^(+)T细胞在高级别宫颈鳞状上皮内病变与早期宫颈癌发病中的作用研究

目的:探讨阴道灌洗液中CD4^(+)与CD8^(+)T细胞亚群分布及局部炎症因子水平在高级别宫颈鳞状上皮内病变(high-grade cervical squamous intraepithelial lesions,HSIL)与早期宫颈鳞癌发病中的作用。方法:收集桂林市人民医院高危型人类乳头状瘤病毒(high-risk human papilloma virus,HR-HPV)感染的HSIL患者120例和早期宫颈癌(cervical cancer,CC)患者144例的临床资料。并随机选取未感染HR-HPV的健康女性60例作为对照组。比较3组患者的临床资料、血清和宫颈灌洗液炎症因子(IL-2、INF-γ、IL-10、TNF-α)、CD4^(+)与CD8^(+)T细胞分布与比值。多因素逻辑回归分析HSIL进展至早期CC的影响因素,绘制ROC及校准图对模型评估。结果:对照组、HSIL组与早期CC组患者血IL-2、INF-γ、IL-10、TNF-α水平、CD4^(+)细胞分布、CD8^(+)T细胞分布与CD4^(+)/CD8^(+)比值比较,差异均无统计学意义(均P>0.05);3组患者阴道灌洗液中IL-2、INF-γ、IL-10、TNF-α水平、CD4^(+)细胞分布、CD8^(+)T细胞分布与CD4^(+)/CD8^(+)比值比较,差异均具有统计学意义(均P<0.05),且早期CC组高于HSIL组及对照组(均P<0.05),HSIL组高于对照组(P<0.05)。逻辑回归分析显示,模型2中产次>2次(OR=3.119,95%CI:4.353~6.737)与阴道灌洗液CD4^(+)T细胞百分比(OR=0.327,95%CI:0.188~0.478)(P<0.001,AUC=0.908),模型3中CD4^(+)/CD8^(+)(OR=0.809,95%CI:0.356~1.868)(P<0.001,AUC=0.873)对HSIL发展至早期CC有独立影响;两模型ROC曲线无明显差异(Z=1.550 4,P=0.121)。模型3中仅用CD4^(+)/CD8^(+)就能良好预测,该模型为优,该模型校准曲线与标准曲线接近。结论:HR-HPV感染后,宫颈局部免疫状态参与HSIL及HSIL进展至早期CC,且CD4^(+)/CD8^(+)T细胞比值可作为其独立保护因素。

外用红色诺卡氏菌细胞壁骨架治疗子宫颈锥切术后高危型HPV持续感染的临床疗效分析

目的:探讨外用红色诺卡氏菌细胞壁骨架(Nr-CWS)治疗子宫颈锥切术后高危型人乳头瘤病毒(HR-HPV)持续感染的临床疗效。方法:选择2019年1月至2021年1月因HR-HPV感染引起子宫颈高级别上皮内病变(HSIL),于青岛大学附属青岛妇女儿童医院行子宫颈冷刀锥切术,术后6个月复查HR-HPV持续感染的69例患者为研究对象,并随机分为治疗组(Nr-CWS治疗1个疗程,36例)和对照组(仅观察,33例)。统计患者治疗有效率、阴道微生态变化及副反应发生的情况。结果:①69例患者中,治疗组治疗有效率(80.56%)明显高于对照组(39.39%),差异有统计学意义(P<0.05)。②治疗组乳杆菌患者的比率较对照组增加明显(77.78%vs.45.45%,P<0.05);治疗组pH值≥4.6、白细胞酯酶(LE)阳性患者的比率较对照组及治疗前均有明显降低,差异有统计学意义(P<0.05)。③治疗组36例患者中发热5例,下腹坠胀感5例,腹泻1例,皮疹1例。结论:Nr-CWS治疗子宫颈锥切术后持续HR-HPV感染疗效较好,阴道微生态环境指标(乳杆菌、LE、pH值≥4.6)改善明显,且无严重副反应发生,但仍需从卫生经济学角度出发,根据患者情况综合考虑。

高级别宫颈鳞状上皮内病变的相关治疗进展

宫颈鳞状上皮内病变是宫颈癌的前期病变,其诊断和治疗一直是医学研究的重要课题。目前针对高级别宫颈鳞状上皮内病变的治疗策略主要包括保守治疗和手术治疗,其中手术治疗在临床被广泛应用,但因育龄期女性担忧有创手术治疗的并发症,对保守治疗的研究仍在继续。本文综述近年来高级别宫颈鳞状上皮内病变的主要治疗方法(如药物治疗、消融治疗和手术治疗)、术后随访策略及预防性疫苗的接种。

个体化量化宫颈锥切术治疗阴道镜检查不充分的子宫颈鳞状上皮内病变的疗效分析

目的 分析对阴道镜检查不充分的子宫颈鳞状上皮内病变(SIL)行个体化量化宫颈锥切术的疗效。方法 192例围绝经期及绝经后阴道镜检查不充分的SIL患者作为研究对象,术前均经B超测量宫颈管长度,然后行个体化量化宫颈锥切术,其中108例行子宫颈冷刀锥切术(CKC)作为CKC组,84例行子宫颈环形电切术(LEEP)作为LEEP组。对宫颈锥切术后病理为高级别鳞状上皮内病变(HSIL)的52例患者追加筋膜外全子宫切除术或宫颈补切术。分析宫颈锥切术后切缘阳性的单因素及HSIL追加筋膜外全子宫切除术或宫颈补切术后残留宫颈病理情况。结果 192例SIL患者行宫颈锥切术后切缘阳性35例,其中CKC组术后切缘阳性率为18.52%(20/108), LEEP组术后切缘阳性率为17.86%(15/84),两组术后切缘阳性率比较,差异无统计学意义(P>0.05)。单因素分析显示,切缘阳性患者病变累及腺体占比65.71%(23/35)高于切缘阴性患者的43.95%(69/157)(P<0.05);而切缘阳性患者与切缘阴性患者的手术方式、高危人类乳头瘤病毒(HPV)感染情况、细胞学、阴道镜病理级别比较差异无统计学意义(P>0.05)。对宫颈锥切术后病理为HSIL的52例患者追加手术, 42例有子宫切除的要求或指征,追加了筋膜外全子宫切除术,其中CKC组18例, LEEP组24例。其余10例据术后病理提示阳性部位追加宫颈补切术,其中CKC组7例, LEEP组3例。追加手术后CKC组及LEEP组残留宫颈阳性率比较差异无统计学意义(P>0.05)。结论 个体化量化的两种宫颈锥切手术治疗围绝经期及绝经后阴道镜检查不充分的SIL疗效无显著性差异,对有保留子宫要求的患者, LEEP也是切实可行的治疗方法。

FAM83A与β-catenin在宫颈病变组织中的表达差异

目的探讨83序列相似成员A(FAM83A)与β-连环蛋白(β-catenin)在宫颈病变组织中的表达差异及潜在临床意义。方法利用UALCAN和GEPIA2.0在线数据库分析FAM83A在正常宫颈和宫颈鳞癌(CSCC)中的表达差异及FAM83A表达与CSCC患者预后的关系,使用LinkedOmics数据库分析FAM83A mRNA共表达基因,利用R语言进行KEGG富集分析。免疫组化方法检测60例正常宫颈组织、80例低级别鳞状上皮内病变(LSIL)、90例高级别鳞状上皮内病变(HSIL)、70例CSCC中FAM83A与β-catenin表达情况。分析FAM83A、β-catenin表达与临床病理特征之间的关系及FAM83A与β-catenin表达的相关性。结果UALCAN数据库分析显示FAM83A在CSCC组织中高表达,GEPIA 2.0数据库分析提示FAM83A高表达者预后不良。LinkedOmics数据库进行KEGG富集分析提示FAM83A的表达与Wnt/β-catenin信号通路的异常激活呈正相关。FAM83A在CSCC中的表达率高于LSIL和正常宫颈组织(P<0.001),而与HSIL相比差异无统计学意义(P=0.401);FAM83A的表达与年龄无相关性(P=0.231),与分化程度(P=0.001)和临床分期(P=0.038)的相关性差异有统计学意义。β-catenin在CSCC中的异常表达率高于LSIL和正常宫颈组织(P<0.001),而与HSIL相比差异无统计学意义(P=0.734);β-catenin的表达与年龄无关(P=0.088),与分化程度(P=0.001)和临床分期(P<0.001)有关,FAM83A与β-catenin表达具有正相关性(P<0.05)。结论FAM83A与β-catenin在HSIL及CSCC组织中均高表达,两者之间表达存在正相关性。FAM83A的高表达与CSCC患者预后存在一定的相关性,可作为判断CSCC预后的潜在标志物。

重组人干扰素α-2b凝胶对宫颈鳞状上皮内病变人乳头瘤病毒感染患者免疫功能及阴道微生态恢复情况的影响

目的探讨宫颈鳞状上皮内病变人乳头瘤病毒(HPV)感染患者应用重组人干扰素α-2b凝胶治疗的临床效果。方法选取2020年2月至2023年2月丽水市妇幼保健院收治的116例宫颈鳞状上皮内病变HPV感染患者作为研究对象。采用随机数字表法将其分为A组和B组,每组58例。A组给予聚甲酚磺醛栓,B组在A组基础上给予重组人干扰素α-2b凝胶。比较两组治疗3个月后的临床疗效、阴道微生态恢复情况,治疗前、治疗3个月后的免疫功能、C-反应蛋白(CRP)、Toll样受体2(TLR2)、白介素-17(IL-17)、转化生长因子-β(TGF-β)、干扰素-γ(IFN-γ)水平。结果治疗3个月后,B组总有效率高于A组(P<0.05)。治疗3个月后,两组的外周血CD3^(+)、CD4^(+)水平均比治疗前高,且B组大于A组(P<0.05);两组外周血CD8^(+)、辅助性T细胞17(Th17)、调节性T细胞(Treg)、Th17/Treg水平均比治疗前低,且B组低于A组(P<0.05)。治疗3个月后,B组阴道微生态正常或恢复及乳酸杆菌中量或大量的患者占比均高于A组,B组阴道pH低于A组(P<0.05)。治疗3个月后,两组血清TLR2、CRP、TGF-β、IL-17、IFN-γ水平均低于治疗前,且B组小于A组(P<0.05)。结论宫颈鳞状上皮内病变HPV感染患者应用重组人干扰素α-2b凝胶治疗可有效促进阴道微生态恢复,调节相关因子水平,减轻炎症反应,改善免疫功能,提高治疗效果。