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.

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.

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.

Clinical Value of Human Papillomavirus E6/E7 mRNA Testing in Patients with Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion

Objective: To explore the clinical significance of the quantitative detection of human papillomavirus(HPV) E6/E7 mRN A in triage of patients with atypical squamous cells of undetermined significance(ASC-US) and low-grade squamous intraepithelial lesion(LSIL).Methods: A cross-sectional screening study was conducted among women who underwent outpatient gynecological screening at the Obstetrics and Gynecology Hospital of Fudan University from September 2015 to July 2016. A total of 500 patients from our hospital with ASC-US or LSIL based on cytology testing were subjected to HPV DNA and HPV E6/E7 mRNA quantitative analysis.Results: The specificity of the HPV E6/E7 mRNA test for detecting ≥high-grade squamous intraepithelial lesion(HSIL+) was statistically higher than that of the HPV DNA test(61.3% vs. 40.0%, P< 0.05), whereas there was no significant difference in the sensitivity of HPV E6/E7 mRNA test and HPV DNA test(90.0% vs. 95.0%, P > 0.05). The positive rates of HPV in the participants tested by HPV E6/E7 mRNA and HPV DNA were, respectively, 42.8%(214/500) and 62.8%(314/500), with statistical significance(P < 0.05).Conclusions: The HPV E6/E7 mRNA test was slightly less sensitivity than that of the HPV DNA test for diagnosing HSIL+ in patients with ASC-US and LSIL, but the difference was not significant, although the specificity of the former was significantly higher. HPV E6/E7 mRNA detection can effectively reduce overdiagnosis and overtreatment of patients with ASC-US and LSIL and has important clinical value in triage of patients with ASC-US and LSIL.

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.

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.

Topical 5‑aminolevulinic acid‑mediated photodynamic therapy versus loop electrosurgical excision procedure in the treatment of cervical intraepithelial neoplasia

Objective To compare effectiveness of topical 5-aminolevulinic acid-mediated photodynamic therapy(5-ALA PDT)and loop electrosurgical excision procedure(LEEP)among patients with cervical intraepithelial neoplasia(CIN).Methods We retrospectively identified patients who underwent either 5-ALA PDT or LEEP from Sep.2012 to Dec.2019 in Chinese PLA general hospital.Patients’outcomes were compared according to the HPV genotyping,cytologi-cal tests within 3–6-month follow-up post-treatment,the pathological examination would be performed if the cyto-logical results indicated the risk of CIN.Propensity score matching(PSM)was adapted to pair the baseline.Complete remission(CR),partial remission(PR)and the remission rate of HPV infections were used to evaluate the efficacy of 5-ALA PDT versus LEEP.Results In total,30 pairs were matched as the matching tolerance was set as 0.03.There was no significant difference about the CR and PR between 5-ALA PDT and LEEP group(73.33%vs 84.00%,P=0.340;3.33%vs 4.00%,P=1.000).Among different CIN group,there was no statistic difference between 5-ALA PDT and LEEP.Moreover,in terms of HPV remission rate,5-ALA PDT showed the same efficacy as LEEP(59.26%vs 53.85%,P=0.691).Conclusions In essence,topical 5-ALA PDT emerges as a non-invasive,repeatable procedure with minimal side effects for cervical lesions,preserving cervical structure.Overall,the efficacy of 5-ALA PDT is comparable to LEEP in achieving successful outcomes.

子宫颈鳞状上皮内病变中PYCR2、CA125及ATG-12的表达及意义

目的探讨吡咯啉-5-羧酸还原酶2(PYCR2)、糖类抗原125(CA125)、自噬相关蛋白-12(ATG-12)在子宫颈鳞状上皮内病变(SIL)诊断中的价值。方法于2020年1月至2021年12月在南通市肿瘤医院收集子宫颈组织样本共336例,其中正常子宫颈131例,低级别鳞状上皮内病变(LSIL)91例,高级别鳞状上皮内病变(HSIL)114例。分别检测各组中PYCR2、CA125、ATG-12的表达水平,并分析PYCR2、CA125、ATG-12与SIL的相关性及三者联合检测在子宫颈SIL诊断中的价值。结果LSIL组及HSIL组中PYCR2及CA125的阳性检出率均高于正常子宫颈组(χ^(2)值分别为34.98、51.03,P<0.05);LSIL组及HSIL组中ATG-12的阳性检出率低于正常子宫组(χ^(2)值为61.83,P<0.05);相关性分析结果显示,PYCR2及CA125的阳性检出率与SIL病理分级(LSIL与HSIL)呈显著正相关关系(r=0.321,P<0.05;r=0.387,P<0.05),ATG-12阳性率与SIL病理分级呈显著负相关关系(r=-0.429,P<0.05)。PYCR2、CA125、ATG-12三者联合诊断SIL的AUC为0.996。结论SIL中PYCR2、CA125以及ATG-12的表达水平发生改变,三种指标联合预测模型效果良好,可能作为SIL诊断评估的标志物。

Prognostic value of human papillomavirus 16/18 genotyping in low-grade cervical lesions preceded by mildly abnormal cytology

Histological low-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grade 1 （LSIL/CIN1） preceded by normal or mildly abnormal cytology is recommended for conservative follow-up, with no separated management. In this study, we assessed the triage value of human papillomavirus （HPV） 16/18 genotyping in 273 patients with LSIL/CINI. HPV16/18 genotyping was performed at baseline and follow-up was at 6-monthly intervals for up to 2 years. At each follow-up, women positive for cytology or high-risk HPV （hrHPV） were referred for colposcopy. Enrollment cytology, HPV16/18 genotyping, and questionnaire-obtained factors were linked to the 2-year cumulative progression rate. Univariate and multivariate analyses were performed taking into account time-to-event with Cox proportional hazard regression. The results showed that 190 cases （69.6%） regressed, 37 （13.6%） persisted, and 46 （16.8%） progressed. HPV16/18 positivity （hazard ratio （HR）, 2.708; 95% confidence interval （CI）, 1.432-5.121; P=-0.002） is significantly associated with higher 2-year cumulative progression rate. Sub-analysis by enrollment cytology and age restricted the positive association among patients preceded by mildly abnormal cytology and aged 30 years or older. Immediate treatment is a rational recommendation for the high-risk subgroup, when good compliance is not assured.

透明质酸合成酶1和ATP酶磷脂转运10a基因甲基化定量检测在宫颈癌早期诊断中的应用价值

目的探讨透明质酸合成酶1(HAS1)、ATP酶磷脂转运10a(ATP10a)基因甲基化定量检测在宫颈癌早期诊断中的应用价值。方法选取2022年2—9月于秦皇岛市第一医院就诊,存在细胞学异常和/或高危型人乳头瘤病毒(HR-HPV)感染,且具有明确组织学病理结果的145例患者,采用实时荧光定量甲基化特异性PCR(QMSP)检测HAS1、ATP10a基因在不同程度宫颈病变患者宫颈脱落细胞中的甲基化水平。以活检病理检查结果为金标准,确定HAS1、ATP10a基因甲基化诊断宫颈高级别鳞状上皮内病变(HSIL)+宫颈鳞癌(SCC)的临界值,并依据临界值将定量资料转换为定性资料,采用灵敏度、特异度、阳性预测值、阴性预测值及受试者工作特征(ROC)曲线下面积(AUC)等指标评估各种筛查方法诊断HSIL+(包括HSIL+SCC)的效能。结果纳入了77例宫颈低级别鳞状上皮内病变(LSIL)-患者(病理检查结果为正常/宫颈炎,LSIL),68例HSIL+患者(病理检查结果为HSIL,SCC)。在LSIL-组,HAS1、ATP10a基因甲基化水平分别为0.067(0.015,1.920),0.024(0.008,0.129),均低于HSIL+组的1.509(0.062,1080.749),1.042(0.011,526.086),组间比较差异均有统计学意义(均P<0.05)。选取0.185、0.197分别作为HAS1、ATP10a基因甲基化阳性的临界值,在LSIL-组中,液基薄层细胞学检查(TCT)结果异常率,HR-HPV检测阳性率,HAS1+ATP10a基因甲基化阳性率,HR-HPV检测联合HAS1+ATP10a基因甲基化阳性率分别为50.65%、85.71%、38.96%、36.36%,均显著低于HSIL+组(69.12%、95.59%、79.41%、75.00%)。HR-HPV检测、TCT、HAS1+ATP10a基因甲基化、HR-HPV检测联合HAS1+ATP10a基因甲基化诊断HSIL+的灵敏度分别为95.59%、69.12%、79.41%、75.00%,特异度分别为14.29%、49.35%、61.04%、63.64%,阳性预测值分别为49.62%、54.65%、69.05%、64.56%,阴性预测值分别为78.57%、64.41%、77.05%、74.24%,AUC分别为0.549、0.592、0.702、0.693。结论宫颈脱落细胞中HAS1、ATP10a基因甲基化水平随宫颈病变严重程度加重而升高,HAS1、ATP10a基因甲基化检测HSIL+病变具有较高的临床价值,有望成为早期诊断宫颈癌的方法。

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。

HPVL1壳蛋白及p16蛋白在高危型HPV持续感染的宫颈低级别鳞状上皮内病变患者临床转归中的意义

目的探讨人乳头瘤病毒(human papilloma virus,HPV)L1壳蛋白及p16蛋白在高危型HPV持续感染的宫颈低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)患者临床转归中的意义。方法选取2022年1月至7月在中山市博爱医院妇科宫颈病变中心就诊的114例高危型HPV持续感染且病理确诊为LSIL患者的宫颈组织进行HPV L1、p16免疫组化分析及随访。结果114例LSIL患者累计进展率21.93%,HPV L1、p16阳性率分别为25.44%、39.47%。单独检测中,HPVL1(+)表达者的消退率最高达68.97%,与进展组、持续组间的差异有统计学意义(P<0.05);联合检测中,HPVL1(+)/p16(+)、HPVL1(+)/p16(–)、HPVL1(–)/p16(+)表达者疾病累计消退率分别为60.00%、78.57%、43.64%,与累计进展率、持续率的差异均有统计学意义(P<0.05)。分层分析发现,单独检测中,HPVL1(+)表达者在第24个月时的消退率高于p16(+)表达者,差异有统计学意义(P<0.05)。联合检测中,HPVL1(–)/p16(+)表达者在第6、12个月时的进展率高于其他患者;而HPVL1(+)/p16(–)表达者在第24个月时的消退率高于其他组,差异均有统计学意义(P<0.05)。二分类Logistic回归分析结果表明,HPV16/18、p16(+)是LSIL进展的危险因素,OR分别为3.242(95%CI:1.261~8.336)、2.714(95%CI:1.055~6.980)。结论高危型HPV持续感染型别分析、HPVL1壳蛋白及p16蛋白免疫组化检测在高危型HPV持续感染的LSIL患者临床转归中有一定临床价值,有助于指导临床医师对高危型HPV持续感染的LSIL患者进行个体化随访及分流管理。

重组人干扰素α-2b凝胶联合匹多莫德治疗宫颈低级别鳞状上皮内病变的临床研究

目的评估重组人干扰素α-2b凝胶联合匹多莫德治疗宫颈低级别鳞状上皮内病变(LSIL/CIN1)的临床疗效。方法选取2020年1月—2024年1月聊城市第二人民医院收治的88例LSIL/CIN1患者。按随机数字表法分为对照组和PID组,各44例。对照组给予重组人干扰素α-2b凝胶治疗,PID组在对照组基础上给予匹多莫德治疗。比较两组患者的临床疗效,治疗前后的阴道微生态情况、免疫功能、灌洗液炎症水平及不良反应发生率。结果PID组的治疗总有效率高于对照组(P<0.05)。PID组的阴道微生态恢复率高于对照组(P<0.05),PID组阴道分泌物pH值、Nugent评分均低于对照组(P<0.05)。PID组治疗前后CD4^(+)、CD8^(+)、Treg、Th17的差值均高于对照组(P<0.05)。PID组治疗前后IFN-γ、IL-10和TNF-α的差值均高于对照组(P<0.05)。两组患者的不良反应发生率比较,差异无统计学意义(P>0.05)。结论重组人干扰素α-2b凝胶联合匹多莫德治疗LSIL/CIN1患者,能有效改善患者免疫水平,减少炎症反应,且安全性好,适合在临床上广泛应用。

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。

P16、Ki-67诊断宫颈鳞状上皮内病变价值及与高危型HPV感染关系

目的:研究P16、Ki-67诊断宫颈鳞状上皮内病变价值及与高危型人乳头瘤病毒(HPV)感染关系。方法:选取2022年2月-2024年2月本院收治的确诊宫颈鳞状上皮内病变患者150例纳入病例组,同期体检健康女性150例纳入健康组,以阴道镜检查和组织病理学检查结果作为金标准,采用液基薄层细胞检测(TCT)、HPV DNA检测、测定P16、Ki-67阳性表达情况,绘制受试者工作特征(ROC)曲线分析P16、Ki-67对宫颈鳞状上皮内病变的诊断价值;Spearman相关系数分析病例组P16、Ki-67阳性表达与HPV感染相关性。结果:病例组P16阳性表达(94.7%)、Ki-67阳性表达(93.3%)均高于对照组(3.3%、5.3%)(P<0.05);P16、Ki-67检出宫颈鳞状上皮内病变的准确率分别为;ROC曲线分析P16、Ki-67诊断宫颈鳞状上皮内病变的曲线下面积分别为0.957、0.940,敏感度94.7%、93.3%,特异度96.7%、94.7%;宫颈鳞状上皮内病变患者P16阳性表达、Ki-67阳性表达与HPV感染均呈正相关(r=0.705、0.726,均P<0.05)。结论:宫颈鳞状上皮内病变患者P16、Ki-67阳性率均异常升高,且阳性率与HPV感染呈正相关,对宫颈鳞状上皮内病变诊断价值较高。

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。

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。

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。