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.

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.

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.

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 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.

Clinical applicability of immunotherapy of cervical intraepithelial neoplasia

Immunotherapy for cervical intraepithelial neoplasia （CIN） has not yet reached clinical applicability, but seems sensible and shows promising preliminary results. One of the most promising forms of immunotherapy for CIN may currently be imiquimod, because of its established role in other human papillomavirus （HPV）-induced genital conditions, its promising treatment effcacy in high-grade CIN, and its off-label availability. Although imiquimod cannot yet replace the current gold standard treatment for CIN [ i.e. , large loop excision of the transformation zone （LLETZ）] in all patients, it may be considered in subgroups of patients; for example, young women who may wish to become pregnant in the future, or patients with recurrent CIN lesions in whom a second LLETZ is to be avoided. Immunotherapy of CIN could be extended to post-treatment vaccination, in order to prevent new HPV infections and disease recurrence.

Risk assessment and triage strategy of cervical cancer primary screening on HPV integration status:5-year follow-up of a prospective cohort study

Objective:We investigated the relation between man papillomavirus(HPV)integration status and the immediate risk of cervical intraepithelial neoplasia(CIN),as well as the triage strategy based on HPV integration test.Methods:4086 women aged 20 to 65 years in China were enrolled in 2015 for a prospective,population-based,clinical observational study to evaluate the triage performance of HPV integration.Cervical exfoliated cells were collected for HPV testing and cytologic test.If high-risk HPV was positive,HPV integration test was performed at baseline,2-year and 5-year follow-up.Results:At baseline,HPV integration was positively correlated with the severity of cervical pathology,ranging from 5.0%(15/301)in normal diagnosis,6.9%(4/58)in CIN1,31.0%(9/29)in CIN2,70%(14/20)in CIN3,and 100%(2/2)in cervical cancer(P<0.001).Compared with cytology,HPV integration exhibits comparable sensitivity and negative predictive value for the diagnosis of CIN3+,higher specificity(92.8%[90.2%-95.4%]vs.75.5%[71.2%-79.8%],P<0.001)and higher positive predictive value(36.4%[22.1%-50.6%]vs.15.2%[8.5%-21.8%],P<0.001).HPV integration testing strategy yielded a significantly lower colposcopy referral rate than cytology strategy(10.7%[44/410]vs.27.3%[112/410],P<0.001).The HPV integration-negative group exhibited the lowest immediate risk for CIN3+(1.6%)and accounted for the largest proportion of the total population(89.3%),when compared with the normal cytology group(risk,1.7%;proportion,72.7%).Conclusion:As a key molecular basis for the development of cervical cancer,HPV integration might be a promising triage strategy for HPV-positive patients.

Clinical evaluation of HPV DNA test combined with liquid-based cytology in the diagnosis of cervical disease

Objectives: To evaluate the sensitivity and accuracy of the HPV DNA test in conjunction with thin prep cytology test as a screening method of human papillomavirus (HPV) infection. To study either the cervical erosion is related to high risk HPV infection or to determine the mean age distribution that is more prone to HPV infection. Material and Methods: The study is a retrospective cohort implemented to determine the real performance of liquid based medium and HPV DNA testing combined in second clinical hospital of Jilin University Changchun, China. The study group included total 150 patients from January 1, 2011 to December 30, 2012. A computerized search identified patients with thin prep test results and high risk HPV DNA testing during a 2-year period was recruited. The patients were chosen after proper speculum examination followed by thin prep cytology (TCT) and HPV DNA test. Cytologic specimens were obtained with endocervical brush, which was rinsed into the vial of Cytyc. The residual samples after the cytology report were taken for reflex HPV DNA test. The manufacture protocol was followed for HPV DNA testing using Hybrid Capture II. Colposcopic biopsy was performed for the diagnosis purpose, in patients who had atypical squamous cells of undeter-mined significance (AUS-US), low grade intraepithelial lesion (LSIL) or high-grade intraepithelial lesion (HSIL) in cytology and with positive results of highrisk HPV DNA. The diagnostic criteria were based on the Bethesda System (TBS). Findings: The high risk HPV positive women with abnormal cytology had a CIN I risk of 73 (86%), whereas 35 (23.3%) high-risk HPV positive women out of 109 (72.7%) normal cytology who underwent histological biopsy had CIN I 16 (10.7%). The risk for cervical intraepithelial neoplasia (CIN) in women with high-risk HPV positive with normal cytology was higher among women invited for the first time 31 - 40 years of age 12 (8%) than among older women 1 (0.7%). Out of 44 (29.3%) women who had I degree erosion with 6 (14%) positive HPV DNA test 38 (86%) had a normal histology biopsy showing no statically significant between them. Conclusion: The data confirm that HR-HPV DNA testing is much more sensitive than cytology alone and that HPV DNA testing helps in identifying women with high risk of serious cervical disease in an efficient and medically acceptable manner. The other most significant advantage of this cervical cancer screening method is that women who are HPV DNA positive can easily and quickly referred for colposcopic examination (within one year), which could identify the precancerous and cancer stage. And those who are HPV DNA negative can safely have much longer screening intervals saving considerable costs. With mean age being 38 ± 10 years, age older than 30 years should undergo HPV DNA testing with cytology triage in primary screening. But in woman younger than 30 years using HPV DNA assay, as an initial screening step can increase the prevalence of abnormal smears and the positive predictive value of HPV followed by TCT. However, close follow-up is essential if the initial biopsy is negative because a considerable number of women may have HPV infection positive in subsequent studies.

乌鲁木齐市11654例女性HPV分型及定量检测结果分析

目的分析新疆乌鲁木齐市女性人乳头瘤病毒(HPV)感染特点及HPV分型定量检测对宫颈病变的预测性能。方法收集2022年1-12月于新疆医科大学第一附属医院妇科就诊并进行HPV检测的11654例女性的HPV检测结果。根据年龄将所有就诊者分为低龄组(≤29岁)、青龄组(>29~39岁)、中龄组(>39~49岁)、中老龄组(>49~59岁)和老龄组(>59岁)。其中1483例患者同时进行阴道镜活检和宫颈组织病理学检测,根据组织病理学诊断结果,将1483例患者分为宫颈炎、宫颈上皮内瘤变(CIN)Ⅰ、CINⅡ、CINⅢ和宫颈癌,将CINⅠ及以上命名为CIN阳性,CINⅡ及以上命名为CINⅡ+,CINⅢ及以上命名为CINⅢ+。采用实时荧光定量PCR检测HPV亚型及病毒载量,比较不同民族、年龄、宫颈疾病女性HPV的检测结果,比较不同宫颈病变患者主要的HPV亚型病毒载量水平,采用受试者工作特征(ROC)曲线确定主要的HPV亚型预测CINⅡ+的病毒载量阈值。结果在11654例就诊者中,HPV感染率为30.60%,单一亚型感染占77.73%。HPV16、52、58是CIN阳性患者感染的主要型别,分别占38.89%、14.90%、11.11%。汉族、维吾尔族、回族和哈萨克族女性HPV感染率分别为31.89%、24.39%、31.76%和27.88%,4个民族HPV感染率比较,差异有统计学意义(χ^(2)=40.929,P<0.001)。在11654例就诊者中,老龄组HPV感染率最高(34.04%),中龄组HPV感染率最低(26.41%),不同年龄组间HPV感染率比较,差异有统计学意义(χ^(2)=37.754,P<0.001)。在396例CIN阳性患者中,高危型HPV和单一亚型感染率随CIN级别升高而升高(χ^(2)趋势=9.994、7.233,P<0.01)。CINⅡ+患者HPV16、52、58病毒载量与宫颈炎患者相比,差异均有统计学意义(P<0.05);且HPV16、52、58病毒载量预测CINⅡ+的最佳截断值分别为4.382、3.694、4.114 copy/104个细胞(经lg转化)。结论新疆乌鲁木齐市女性HPV感染以单一亚型感染为主,HPV16、52、58是主要的感染型别,并且HPV标准化定量具有作为宫颈高级病变预测标志物的潜力。

HPVL1蛋白、TRIM22、HER-2联合检测在HPV阳性宫颈上皮内瘤变中的早期诊断价值

目的 探讨人乳头瘤病毒LI(HPVL1)蛋白、三结构域家族蛋白22(TRIM22)、人表皮生长因子受体-2(HER-2)联合检测在人乳头瘤病毒(HPV)阳性宫颈上皮内瘤变(CIN)中的早期诊断价值。方法 回顾性选取2021年1月至2023年6月承德医学院附属医院就诊的162例薄层液基细胞学(TCT)检查异常且HPV阳性的CIN患者为研究组,另选取同期经组织病理学诊断为正常宫颈组织的138名对象为对照组。免疫组织化学法检测宫颈组织中HPVL1蛋白、TRIM22、HER-2表达。比较对照组、研究组组织中HPVL1蛋白、TRIM22、HER-2表达,并比较不同分级CIN患者HPVL1蛋白、TRIM22、HER-2表达。多因素Logistic回归模型分析CIN发生的影响因素;受试者操作特征(ROC)曲线分析HPVL1蛋白、TRIM22、HER-2表达对CIN的早期诊断价值。结果 研究组组织中HPVL1蛋白及TRIM22蛋白阳性率分别为34.57%、32.72%,均显著低于对照组(74.64%、71.01%),HER-2阳性率为60.49%,显著高于对照组(10.87%),差异均有统计学意义(P<0.05)。CINⅠ级、CINⅡ级和CINⅢ级HPVL1蛋白和TRIM22阳性率呈下降趋势,HER-2阳性率呈上升趋势(P<0.05)。多因素Logistic回归分析结果显示,宫颈组织中HPVL1蛋白、TRIM22及HER-2表达均为CIN的影响因素(OR=5.110、5.231、9.652,P<0.05)。ROC曲线结果显示,HPVL1蛋白表达诊断CIN的曲线下面积(AUC)为0.700,敏感度为65.43%;TRIM22表达诊断CIN的AUC为0.691,敏感度为67.28%;HER-2表达诊断CIN的AUC为0.748,敏感度为60.49%。三者联合诊断CIN的AUC为0.814,显著高于单独诊断的AUC(P<0.05)。结论 宫颈组织中HPVL1蛋白、TRIM22及HER-2表达影响CIN的发生、发展,三者联合对CIN具有较高的诊断价值。

联合p16、Ki-67免疫组织化学染色在宫颈上皮内瘤变分级诊断中的应用效果观察

[目的]探究与分析联合应用p16、Ki-67免疫组织化学染色对宫颈上皮内瘤变(CIN)分级诊断的影响.[方法]回顾性分析自2019年3月至2021年11月间收治的接受宫颈液基薄层细胞学检查(TCT)且检查结果异常的60例患者的临床资料.全部患者按照苏木精-伊红染色法(HE)结果分为慢性宫颈炎组(n=19)、CINⅠ组(n=15)、CINⅡ组(n=12)、CINⅢ组(n=10)、宫颈癌组(n=4),全部患者均进行了宫颈阴道镜活检、人乳头瘤病毒(HPV)分型检测,并配合采用P16、Ki-67免疫组织化学染色的半定量评分,以判断患者宫颈病变程度.[结果]随着宫颈CIN病变程度的升高,CINⅢ组分别与CINⅠ组、CINⅡ组相比,CINⅡ组与CINⅠ组相比,P16表达阳性程度及Ki-67表达阳性程度升高,差异有统计学意义(P<0.05).慢性宫颈炎组P16、Ki-67免疫组织化学结合半定量评分与HE染色CIN分级诊断结果相符,CINⅠ组、CINⅡ组、CINⅢ组诊断结果相符率为94.59%,差异具有统计学意义(P<0.05).P16呈阳性表达时与HPV感染呈正相关(P<0.05).HPV-16、HPV-18、HPV-35、HPV-39、HPV-51在P16表达阳性与阴性方面差异具有统计学意义(P<0.05).[结论]CIN分级与P16、Ki-67的表达呈正相关,且P16与患者HPV感染有密切的关系.

子宫颈高危型人乳头瘤病毒感染的中西医治疗研究进展

宫颈癌是我国女性第6位高发恶性肿瘤,严重危害女性生命健康,而子宫颈高危型人乳头瘤病毒(HPV)的持续感染是诱发宫颈癌及宫颈上皮内瘤样病变(CIN)的主要因素。由于从病毒感染进展为宫颈癌需要较长时间,针对病因,及时阻断子宫颈高危型HPV感染,有效阻止病情进展,防止宫颈癌的发生尤为重要。西医外用药物、消融及手术治疗存在易复发、出血、感染及术后影响生育功能等并发症,中医辨证论治,在病情不同阶段均可提供有效干预,且中药多靶点,与多个信号通路发生作用,与西医协同治疗可优势互补,提高疗效。通过综述中西医治疗子宫颈高危型HPV的主要方法,为该病临床诊治提供思路,同时综述子宫颈高危型HPV感染实验模型及中医药抗高危型HPV感染作用机制,为进一步实验研究提供参考。

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。

HPV感染相关CIN患者血清HLA-E和HLA-G表达与疾病进展及治疗后复发的相关性

目的探讨人乳头瘤病毒(HPV)感染相关宫颈上皮内瘤变(CIN)患者血清人类白细胞抗原E(HLA-E)、人类白细胞抗原G(HLA-G)表达及临床意义。方法选取2021年6~12月在河北中石油中心医院治疗的HPV感染相关CIN患者120例作为观察组,选取同期无HPV感染的CIN患者60例作为对照组,检测两组血清HLA-E和HLA-G表达水平,分析血清HLA-E和HLA-G表达与患者临床资料、治疗后复发的关系。结果观察组血清HLA-E和HLA-G水平分别为(75.59±18.28)pg/mL和(30.20±9.92)ng/mL,高于对照组,差异有统计学意义(P<0.05)。观察组CIN分级Ⅱ/Ⅲ级患者血清HLA-E和HLA-G分别为(83.33±13.90)pg/mL和(34.54±7.18)ng/mL,高于CIN分级Ⅰ级(P<0.05);观察组高危型HPV感染者血清HLA-E和HLA-G分别为(78.82±17.70)pg/mL和(32.23±9.43)ng/mL,高于低危型HPV感染者(P<0.05)。观察组血清HLA-E和HLA-G表达与CIN分级呈正相关(P<0.05)。复发患者治疗后1周血清HLA-E和HLA-G分别为(68.32±8.73)pg/mL和(24.43±5.58)ng/mL,高于未复发患者(P<0.05)。结论HPV感染相关CIN患者血清HLA-E和HLA-G表达与CIN分级呈正相关,同时与患者治疗后复发有一定关系。

经阴道分离膀胱直肠间隙的宫颈LEEP术后HPV转阴情况及生育能力分析

目的探讨子宫颈高级别鳞状上皮内病变(high-grade cervical intraepithelial neoplasia,HSIL)患者行经阴道分离膀胱直肠间隙的宫颈环形电切术(loop electrosurgical excision procedure,LEEP)后人乳头状瘤病毒(human papillomavirus,HPV)转阴情况及生育力。方法收集2019年1—12月在复旦大学附属妇产科医院行经阴道分离膀胱直肠间隙的宫颈LEEP术患者53例,术后行子宫颈脱落细胞学检查、HPV检测和阴道镜下子宫颈活检,随访时间分别为6、12和24个月。分析患者术前HPV感染分布及保育成功率,经阴道分离膀胱直肠间隙的宫颈LEEP术后HPV转阴情况,术后切缘阳性和病理类型分布,HPV感染类型对术后切缘阳性的影响及患者术后生育情况。结果53例患者中,94.3%(50/53)存在HPV感染,其中75.5%(40/53)为HPV16/18型感染者,69.8%(37/53)为HPV单一亚型感染,高于混合感染22.7%(12/53);71.7%(38/53)前次LEEP术后切缘阳性,28.3%(15/53)HSIL复发;56.6%(30/53)术后病理HSIL,28.3%(15/53)未发现病理性改变;75.5%(40/53)术后切缘阴性(即保育成功),其中95%(38/40)HPV转阴。比较HPV16/18感染(P=0.196)和HPV感染类型(P=1.000)对术后切缘阳性的影响,差异无统计学意义。5例保育成功的患者在术后完成生育(12.5%,5/40),其中顺产1例,剖宫产4例。5例均为足月分娩,3例行宫颈环扎术,2例患者未行宫颈环扎。结论子宫颈HSIL患者行经阴道分离膀胱直肠间隙的宫颈LEEP术后保育成功率高,术后HPV转阴率高。

宫颈病变筛查中p16/mcm2、HPV检测的临床价值

目的:检测宫颈病变中宫颈脱落细胞p16/微小染色体维持蛋白(mcm2)的表达,探讨p16/mcm2与人乳头瘤病毒(HPV)检测在宫颈病变筛查的临床价值。方法:选取2023年5-10月在徐州市肿瘤医院妇科门诊或病房行宫颈癌筛查并符合入组标准的1045例女性,均行p16/mcm2免疫细胞化学双染检测及HPV检测,对p16/mcm2双染确诊为不明意义的非典型鳞状上皮细胞(ASC-US)及以上病变或HPV16/18阳性者行阴道镜检查、活检宫颈组织送病理检查。结果:p16/mcm2阳性率在HPV阴性组、低危HPV组、其他12种HPV阳性组和HPV16/18阳性组依次递增(P=0.000);p16/mcm2阳性表达在其他12种HPV阳性组和HPV16/18阳性组均高于HPV阴性组[OR=4.28(95%CI 2.02~9.04)、OR=76.64(95%CI 36.05~162.93)],在HPV16/18阳性组均高于其他12种HPV阳性组,且随宫颈病变程度加重p16/mcm2阳性表达增高(均P<0.05)。p16/mcm2检测筛查子宫颈上皮内瘤病变CIN1级、CIN2级和CIN3级的灵敏度和阳性预测值(85.0%、89.1%、94.3%,94.1%、97.0%、97.0%)均高于HPV。结论:p16/mcm2双染和HPV存在相关性,两者均可用于宫颈病变筛查;与HPV检测相比,p16/mcm2双染有较高灵敏度和阳性预测,p16/mcm2双染联合HPV检测有望成为有较好应用前景的宫颈癌筛查方案。

阴道微环境失衡对HPV感染及宫颈病变的影响

目的评估阴道微生态环境失衡对高危型人乳头瘤病毒(HR-HPV)感染、宫颈上皮内瘤变(CIN)及子宫颈癌的影响。方法对接受检查的2469名女性的宫颈脱落细胞进行HPV基因分型检测、阴道微环境常见菌群革兰染色镜检、液基薄层细胞学检测(TCT)和病理活检观察病变组织及细胞形态,根据是否感染HPV、发生CIN或癌变分组,采用χ^(2)或Fisher精确检验及多因素logistics回归分析探讨阴道微环境与HR-HPV感染、CIN的发展以及子宫颈癌之间的关系。结果单一HR-HPV型的阳性率为12.31%,两种及以上的混合感染率为3.85%,以HPV16、HPV52和HPV58亚型多见,38~47岁人群阳性率最高(P<0.05);乳酸杆菌的减少、细菌性阴道病(BV)和杂菌感染在HPV阳性组中的检出率显著高于HPV阴性组(P<0.01),乳酸杆菌的减少和BV是HPV感染的独立危险因素(P<0.05);乳酸杆菌减少、清洁度异常、BV、滴虫和pH异常检出率,CIN或癌变组高于宫颈正常组(P<0.05),乳酸杆菌的减少和清洁度异常是宫颈发生CIN或癌变的独立危险因素(P<0.05)。结论阴道微生物种群的异常,特别是乳酸杆菌数量的减少,可能会增加HR-HPV感染的风险,并促进CIN或癌变的发展。

重组人干扰素α2b凝胶联合LEEP刀宫颈锥切术对宫颈上皮内瘤样病变合并HPV感染患者免疫功能及炎症指标的影响

目的探讨重组人干扰素α2b凝胶联合子宫颈电热圈环切术(LEEP)刀(超高频电波刀)宫颈锥切术对宫颈上皮内瘤样病变(CIN)合并人乳头瘤病毒(HPV)感染患者免疫功能及炎症指标的影响。方法以随机数字表法将2020年1月至2022年1月收治的86例CIN合并HPV感染患者分为对照组和观察组,各43例。对照组采用LEEP刀宫颈锥切术治疗,观察组在对照组基础上联合重组人干扰素α2b凝胶治疗。比较两组的治疗效果。结果观察组的治疗总有效率为97.67%,高于对照组的83.72%(P<0.05)。观察组的阴道微生物恢复率、HPV转阴率均高于对照组,CIN复发率低于对照组(P<0.05)。治疗后,观察组的免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、白细胞介素-12(IL-12)及干扰素-γ(IFN-γ)水平高于对照组,白细胞介素-10(IL-10)水平低于对照组(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论重组人干扰素α2b凝胶联合LEEP刀宫颈锥切术治疗CIN合并HPV感染患者的疗效显著。

宫颈LEEP术后接种HPV疫苗对宫颈上皮内瘤变患者预后的影响研究

目的:探讨宫颈环形电切除术(LEEP)术后接种人乳头瘤病毒(HPV)疫苗对宫颈上皮内瘤变(CIN)患者预后的影响。方法:在江西省信丰县人民医院选取2019年6月—2021年6月收治CIN患者76例,采用Excel表格建立随机数字表法分组,38例观察组与38例对照组,两组均接受LEEP术治疗,观察组术后按0/2/6程序接种二价HPV疫苗,对照组术后不接种HPV疫苗。对比两组患者HPV阳性率变化、术后CIN复发情况及生活质量。结果:两组术后6个月及接种完成后3个月、6个月、12个月HPV阳性率对比,观察组均比对照组低(P<0.05)。两组术后12个月、15个月及18个月CIN复发率对比,观察组均比对照组低(P<0.05)。术后两组生活质量量表(SF-36)得分与术前对比均有所升高,且观察组术后得分升高幅度更显著(P<0.05)。结论:CIN患者LEEP术后接种二价HPV疫苗,能够降低术后HPV阳性率及CIN复发率,提升生活质量,为患者带来福音,值得推广。

Prevalence of high-risk human papillomavirus infection in different cervical lesion among organized health-examination women in Shanghai, China

Background Cervical cancer is the second most common cause of death from cancer among women worldwide. Human papillomavirus （HPV） plays a central role in the etiology of cervical cancer. It is important to describe the prevalence of HPV infection in different types of cervical lesions and to explore the relation between HPV viral load and the severity of cervical lesions. Methods To describe the HPV infection prevalence and viral load in different age groups, we retrospectively investigated 6405 cases of women who were organized by their units to take health-examination. They were given Hybrid Capture II tests between January 2005 and December 2006. The correlation between HPV viral load and pathology was assessed. Results Overall HPV infection prevalence was 29.1% （1864/6405）, while in women 18-20 years old it was 54.4% （31/57）, the highest among all age groups. After declining rapidly, HPV prevalence stabilized at about 30.0% in women aged 30 and older. Of the 6405 women, 1483 women had a colposcopic biopsy and 33.2% （492/1483） were positive for HPV DNA. Twenty-one percent of women with a normal diagnosis （238/1095） had HPV infection, a statistically significantly lower prevalence than in women with cervical lesions, including those with cervical intraepithelial neoplasia （68.8% in CIN1,66.7% in CIN2, and 76.5% in CIN3） or with cervical cancer （94.1%）. The correlation coefficient between viral load and cervical lesion severity was 0.134, which was not statistically significant （P=0.075）. Viral load values in women with CINs and cervical cancer were calculated, and no significant differences were identified. Conclusions The prevalence of high-risk HPV infection among women attending hospitals for health-examination in Shanghai is similar to the worldwide rate. HPV viral load can distinguish cervical lesions from normal individuals but cannot adequately predict the severity of cervical lesions.