高危型人乳头瘤病毒DNA检测在宫颈高度鳞状上皮内病变治疗后随访中的价值

目的探讨高危型人乳头瘤病毒(HPV)DNA检测在宫颈高度鳞状上皮内病变治疗后随访中的作用。方法对2003年1月至2007年12月在广东省人民医院因宫颈癌前病变行宫颈电环切除术的502例妇女的随访资料进行回顾性分析。结果组织病理学证实28例存在病变残留或复发,高危型HPV-DNA检测诊断病变残留或复发的敏感性、特异性、阳性预测值、阴性预测值分别为92.86%,84.18%,25.74%,99.50%。术前HPV负荷量与病变复发或残留之间不存在相关性(P=0.7163)。术后HPV负荷量与病变残留或复发之间存在等级相关(P=0.010)。结论高危型HPV-DNA检测诊断宫颈癌前病变治疗后残留或复发的敏感性及阴性预测值高。术前HPV负荷量与术后病变残留或复发无相关性。术后HPV负荷量越高,术后病变残留或复发率越高。     

子宫颈环形电切术后子宫颈上皮内病变复发的相关影响因素及对策研究

目的探讨宫颈环形电切术(LEEP)术后宫颈上皮内病变复发、残留及其相关危险因素。方法回顾性分析2018年5月至2019年5月在首都医科大学附属北京妇产院妇科微创门诊因CIN行LEEP手术的409例患者的临床及资料,采集患者术前术后TCT、HPV、阴道镜病理及12个月随访结果,分析复发及残留的发生情况及影响因素。结果 409例LEEP术后一年的随访中,复发37例,残留5例,复发率为9.05%,残留率为1.22%。年龄≥35岁、绝经、吸烟、产次≥2、术前高危型HPV阳性、病变级别越高、术后病理切缘阳性、术后高危型HPV持续感染是疾病复发的高危因素(P 0.05)。logistic回归分析显示,术后复发的独立危险因素有:绝经、吸烟史、病变级别、术后病理切缘阳性及术后高危型HPV持续感染(P 0.05)。结论 LEEP术后病变复发的危险因素为绝经、吸烟史、高病变级别、术后病理切缘阳性及术后高危型HPV持续感染。应对不同的危险因素采取个性化的预防措施。     

宫颈上皮内瘤变LEEP术后人乳头瘤病毒感染的临床分析

目的：探讨影响宫颈环形电切术（LEEP）治疗宫颈上皮内瘤变（CIN）术后人乳头瘤病毒（HPV）感染和预后的相关因素。方法：回顾分析2013年1月-2015年12月在中国医科大学附属盛京医院妇科门诊行LEEP术并参与术后随访至少一次的CIN患者临床资料,共297例,分析其临床病理指标、术后HPV分型检测及病变残留或复发等情况。结果：LEEP术后HPV阳性率为14.5%（43/297）。LEEP术后HPV感染与切缘情况、病变累及外阴和/或阴道壁具有相关性（P＜0.05）。术后HPV阳性69.8%（30/43）在首次复查时发现,30.2%（13/43）为HPV首次复查转阴后再次感染。LEEP术后高危型HPV阳性与病变残留或复发具有相关性（r=0.401,P＝0.000）。手术前后HPV同一型别持续感染发生病变残留或复发的风险明显高于HPV不同型别感染（χ2=5.619,P＝0.046）,常见型别是HPV16、HPV58。结论：术前CIN合并阴道上皮内瘤变（VAIN）和/或外阴上皮内瘤变（VIN）及切缘阳性是术后HPV感染的高危因素,LEEP术后HPV分型检测对预测病变残留或复发具有重要作用。     

宫颈上皮内瘤变LEEP术后人乳头瘤病毒感染的临床分析

目的:探讨影响宫颈环形电切术(LEEP)治疗宫颈上皮内瘤变(CIN)术后人乳头瘤病毒(HPV)感染和预后的相关因素。方法:回顾分析2013年1月—2015年12月在中国医科大学附属盛京医院妇科门诊行LEEP术并参与术后随访至少一次的CIN患者临床资料,共297例,分析其临床病理指标、术后HPV分型检测及病变残留或复发等情况。结果:LEEP术后HPV阳性率为14.5%(43/297)。LEEP术后HPV感染与切缘情况、病变累及外阴和/或阴道壁具有相关性(P0.05)。术后HPV阳性69.8%(30/43)在首次复查时发现,30.2%(13/43)为HPV首次复查转阴后再次感染。LEEP术后高危型HPV阳性与病变残留或复发具有相关性(r=0.401,P=0.000)。手术前后HPV同一型别持续感染发生病变残留或复发的风险明显高于HPV不同型别感染(χ2=5.619,P=0.046),常见型别是HPV16、HPV58。结论:术前CIN合并阴道上皮内瘤变(VAIN)和/或外阴上皮内瘤变(VIN)及切缘阳性是术后HPV感染的高危因素,LEEP术后HPV分型检测对预测病变残留或复发具有重要作用。     

人乳头瘤病毒分型检测在临床工作中的应用

持续性高危型人乳头瘤病毒(HPV)感染导致宫颈病变和宫颈癌发生学说的确立,促使高危型HPV检测广泛应用于临床工作中。该文阐述了高危型HPV分型检测在宫颈癌及癌前病变中筛查、非典型鳞状上皮不能明确意义(ASC-US)病人的分层管理、阴道镜检查的适应证、宫颈上皮内瘤变(CIN)治疗后残留或复发病变的预测及随访以及指导HPV疫苗的研究与使用。     

116例宫颈上皮内瘤变1级患者非治疗与治疗后的临床转归

目的探讨宫颈上皮内瘤变1（CIN1）患者的非治疗与治疗后的转归。方法收集在天津市大港医院宫颈癌筛查,并经病理证实为CIN1的116例患者,其中63例未治疗仅随访（非治疗组）,53例患者接受治疗（治疗组）,全部病例随访2年。结果第24个月非治疗组与治疗组CIN1自然消退率61.82%,持续存在率34.55%,进展率为5.45%（均为CIN2,未发现宫颈浸润癌）。非治疗组HPV第24个月高危型HPV阳性率14.55%（8/55）,HR-HPV持续阳性6例,3例进展病例均为HR-HPV阳性。治疗组中物理治疗组1年以后复发率4.88%,采用宫颈锥切或宫颈环形电切（LEEP）者均未发现复发,目前所有患者仍在继续随访。结论多数CIN1病变会自然消退,HPV也自然清除,但对于高危型HPV持续阳性的患者应警惕其进展为高度CIN。对怀疑高度病变的患者宜采用宫颈锥切或环切治疗,以免漏诊;物理治疗复发率高,不宜采用。     

宫颈上皮内瘤变治疗后人乳头瘤病毒的清除及随访

人乳头瘤病毒(HPV)是宫颈癌前病变与宫颈癌的主要致病因素,持续高危型HPV感染是宫颈癌前病变的危险信号。该文介绍了HPV在宫颈病变治疗后的清除及其影响因素,在宫颈病变治疗后的随访中高危型HPV检测对预测宫颈病变的疗效及预后有意义。持续高危型HPV阳性是宫颈上皮内瘤变持续和复发的高危因素。     

宫颈细胞学正常的高危HPV感染妇女病理结局分析

目的:探讨宫颈细胞学正常但高危型HPV感染妇女的宫颈病理结局。方法:回顾分析2014年1月~12月就诊于湖北省妇幼保健院妇科门诊的30岁以上行宫颈细胞学+Cervista高危型HPV联合筛查妇女的临床资料,对细胞学正常但高危型HPV感染且行阴道镜检查的218例妇女取活组织检查,分析其病理结局。结果:218例患者中,宫颈病变占27.5%(60/218),其中宫颈低级别鳞状上皮内病变占11.0%(24/218),宫颈高级别鳞状上皮内病变占13.8%(30/218),宫颈浸润癌占2.8%(6/218)。HPV A9组感染共141例,其中CINⅡ/Ⅲ及以上病变21.3%(30/141),HPV A9组阳性与A9组阴性者比较,CINⅡ/Ⅲ及以上病变检出率比较,差异有统计学意义(P0.05)。结论:即使细胞学检查阴性,对宫颈高危型HPV检测及阳性结果尤其是A9组阳性,应高度重视,立即行阴道镜检查以早期发现宫颈高级别鳞状上皮内病变及宫颈浸润癌。     

高危型HPV DNA检测在宫颈上皮内瘤变及宫颈早期鳞癌锥切术后随访中的应用及意义

目的:探讨高危型HPV(HR-HPV)DNA检测在宫颈上皮内瘤变(CIN)及宫颈鳞癌(ⅠA1期)患者经宫颈冷刀锥切术治疗后随访中的应用及意义。方法:2008年1月至2010年10月我院收治的308例CINⅡ～Ⅲ及宫颈鳞癌(ⅠA1期)患者经宫颈冷刀锥切术治疗后,采用第二代杂交捕获试验(HC2)检测HR-HPV DNA联合液基细胞学随访,观察术后HR-HPV清除及宫颈病变复发情况,并分析术后HR-HPV持续感染及病变持续或复发的相关因素。结果:至随访结束,宫颈锥切术后病变持续或复发者共10例。术后病变持续或复发在HR-HPV持续感染组中明显多于HR-HPV转阴组(P<0.001);术前HR-HPV DNA高负荷、病变累及3～4个象限为术后HR-HPV持续感染的高危因素;术前HR-HPV DNA≥500RIUs/CO是术后病变持续或复发的独立危险因素。结论:HR-HPV持续感染是宫颈锥切术后病变持续或复发的重要因素,术前HR-HPV DNA高负荷是术后HR-HPV持续感染及病变持续或复发的独立危险因素,术后应重点随访。     

HPV基因分型检测在宫颈高级别病变治疗后的应用进展

高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)持续性感染是宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和宫颈癌发生的主要原因。宫颈高级别病变患者在标准治疗后疾病进展风险仍高于正常人群。治疗后HR-HPV阳性、细胞学异常、切缘阳性等是宫颈高级别病变残留/复发的预测因子。HPV基因分型检测能明确治疗后HR-HPV的不同感染状态,有助于检出高风险人群。相较治疗后HR-HPV新发感染和再发感染,同一亚型HR-HPV持续感染与宫颈高级别病变治疗后的疾病残留/复发密切相关。HPV16/18型是宫颈高级别病变患者治疗后最常见的持续感染型别,有更高的疾病残留/复发风险,临床上应加强随访力度。与单纯细胞学、HR-HPV检测相比,随访HR-HPV基因分型能提高预测宫颈高级别病变治疗后疾病残留/复发的敏感度,同时保持相似甚至更高的特异度。     

The Bethesda classification for squamous intraepithelial lesions: histologic, cytologic, and viral correlates.

In applying the Bethesda System of classification to cervical squamous lesions, we evaluated the Papanicolaou smears, cervical biopsies, and human papillomavirus (HPV) DNA status of 76 clinic patients. The biopsy specimens and concurrent Papanicolaou smears were analyzed using criteria for low-grade and high-grade squamous intraepithelial lesions, and the biopsies were analyzed for HPV DNA by in situ hybridization. Two independent observers produced good agreement in both cytologic (kappa = 0.62) and histologic (kappa = 0.71) diagnoses. Predictive values of high-grade cytology (for high-grade histology) were high (0.95 for reviewer 1; 0.97 for reviewer 2), and both high-grade cytology and histology correlated strongly with certain "high-risk" HPV types. In contrast, the predictive value of low-grade cytology for either low-grade histology or HPV types other than "high risk" was poor. This study supports the use of certain histologic criteria for distinguishing squamous intraepithelial lesions into two grades. Limitations in cytologic-histologic correlation appear to reflect the absence of cytologic criteria for distinguishing well-differentiated precursor lesions associated with high-risk HPV types.     

Prognostic markers of high-grade squamous intraepithelial lesions: the role of p16INK4a and high-risk human papillomavirus

BACKGROUND: p16INK4a seems to be an indicator of the grade of Human Papillomavirus-induced lesions and a possible predictor of the lesion evolution. There are few studies about the role of HPV test and p16INK4a in diagnosis of high-grade cervical lesions in South-American women. The aim of the present study was to evaluate the presence of p16INK4a and high-risk HPV-DNA expression in cases diagnosed as squamous intra-epithelial lesion and evaluate their role in the approach of high-grade squamous intra-epithelial lesion. METHODS: p16INK4a and high-risk Human papillomavirus were investigated in 96 samples of the cervix (13 cases of high grade squamous intraepithelial lesions, 26 cases of low grade intraepithelial lesions and 57 normal tissues). The p16INK4a was identified by immunohistochemistry using the p16INK4a kit (E6H4 clone, DakoCytomation, Carpinteria, CA) and Human papillomavirus DNA was classified by hybrid capture (Digene). Associations were evaluated by the KAPPA index. RESULTS: The p16INK4a was detected in 92.3% of the high-grade squamous intraepithelial lesions, in 15.4% of the low-grade and in none of the normal tissues. The sensitivity, specificity, positive predictive value and negative predictive value for high-grade lesion were 92.3%, 100%, 100%, and 98.3%, respectively when considering p16INK4a expression, and 100%, 70.2%, 43.3% and 100%, respectively when considering high-risk HPV. CONCLUSIONS: p16INK4a test was better associated with high-grade intraepithelial lesion (kappa = 0.95) than was the presence of high-risk HPV (kappa = 0.47). Both tests could be complementary to high-grade squamous intra-epithelial lesion screening and help to define the diagnosis of the inconclusive low-grade/high-grade squamous intraepithelial lesion cases.     

High-risk human papillomavirus DNA testing and high-grade cervical intraepithelial lesions

OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in the improvement of the recognition of cervical cancer and precancerous lesions in women with abnormal cervical cytology. METHODS: A total of 2152 women with abnormal cervical cytology were submitted to both HPV DNA testing and biopsy guided by colposcopy and the results were correlated. RESULTS: Positive rate of high-risk HPV DNA in groups of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot exclude high-grade (ASC-H), low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions was 53.7, 53.2, 84.6 and 93.0%, respectively. In each group, the detection rate of grade 2,3 cervical intraepithelial neoplasia (CIN 2,3) or cervical cancer in patients with positive HPV DNA was significantly higher than that with negative HPV DNA (P<0.05). In ASC-US group, the negative predictive value of high-risk HPV DNA testing for detection of CIN 2,3 and cervical cancer was 99.8% and the sensitivity 98%. CONCLUSION: HPV DNA testing is a useful indicator in the management of patients with ASC-US and plays an important role in the evaluation of risk for CIN 2,3 and cervical cancer.     

Immunohistochemical and molecular study of severe cervical dysplasia associated with HPV-83

BACKGROUND: Based on epidemiological data, infections with specific types of HPV can be classified as high-risk (HR), low-risk (LR) or intermediate-risk (IR) HPV depending on the risk of progression to cervical cancer. CASE: A 70-year-old woman consulted for relapse of abnormal cytology with high-grade squamous intraepithelial lesions (HSIL) associated with HPV-83 infection. Histological examination demonstrated high-grade cervical intraepithelial neoplasia (CIN III) with strong and diffuse staining by the P16(INK4a)-specific antibody. CONCLUSION: This patient's intermediate-risk HPV infection (HPV-83) rapidly progressed to severe cervical intraepithelial neoplasia (CIN III) with strong anti-P16(INK4a) immunolabelling. Analysis of the E6 peptide sequence revealed several mutations in one of the two putative zinc finger regions (AA residues 107-135) associated with p53 binding.     

冷刀锥切术切缘阴性的重度宫颈鳞状上皮内瘤变患者的预后影响因素分析

目的探讨冷刀锥切术切缘阴性的重度宫颈鳞状上皮内瘤变（HSIL）患者的预后影响因素。方法回顾分析1999年1月至2004年1月间,卫生部北京医院妇产科266例冷刀锥切手术切缘阴性的HSIL患者的临床资料,分析影响预后的因素,并随访治疗结局。其中宫颈上皮内瘤变（CIN）II20例,CIN11246例（包括原位癌82例）;腺体累及者40例,无腺体累及者226例;257例检测高危型人乳头状瘤病毒（HPV）患者中,高危型HPV阳性244例,阴性13例。结果中位数随访时间46个月,总复发率为8．6％（23／266）,无浸润癌发生。CINⅡ患者中1例（5．0％,1／20）复发,CINⅢ患者（不包括原位癌）中9例（5．5％,9／164）复发,而82例原位癌中13例（15．8％,13／82）复发,原位癌与CINⅡ及CINⅢ（不包括原位癌）患者复发率比较,差异均有统计学意义（P〈0．05）。腺体累及者中7例（17．5％,7／40）复发,无腺体累及者中16例（6．0％,16／226）复发,两者比较,差异有统计学意义（P〈0．05）。高危型HPV阳性者中21例（8．6％,21／244）复发,而13例高危型HPV阴性者中无一例复发,两者比较,差异有统计学意义（P〈0．05）。结论冷刀锥切术切缘阴性的HSIL复发率低;病理分级高和腺体受累是影响疗效及预后的因素。     

高级别宫颈上皮内瘤变治疗及转归预测因素的研究进展

研究已证实宫颈上皮内瘤变是宫颈癌的癌前病变,2014年世界卫生组织（WHO）改变了既往宫颈上皮内瘤变的3级分类法,将其分为低级别鳞状上皮内病变和高级别鳞状上皮内病变两类,其中宫颈高级别鳞状上皮内病变具有癌变潜能,极易进展,使我国女性的生理及心理健康受到严重威胁。目前,高级别鳞状上皮内病变的常用治疗方式为宫颈冷刀锥切术和环形电切术,一般疗效较好,但仍可能发生术中及术后出血、切口感染、宫颈狭窄、子宫内膜异位症和肠道损伤等并发症。相关研究显示,人乳头瘤病毒（HPV）分型、切缘阳性以及绝经状态与术后病变残留、复发、进展等风险密切相关,对宫颈锥切术后不良结局的预测有助于加强对此类患者的集中管理,提前预防并及时阻断病变进展途径,降低宫颈癌的患病率和死亡率。目前,预防性HPV疫苗的安全性和有效性已得到充分肯定,对减少HPV感染、预防术后疾病复发疗效显著,但宫颈已有病变者术后接种疫苗的作用效果尚待进一步探究。     

子宫颈高级别上皮内病变患者的治疗对策及转归

目的通过分析宫颈高级别上皮内病变(HSIL)患者手术前后病理和预后,探讨合适的手术方案。方法对528例阴道镜下活检诊断为宫颈HSIL的患者分别行冷刀锥切术(CKC)(n=353)和环形电切术(LEEP)(n=175),病理回报宫颈HSIL及浸润癌者给予二次手术。比较手术前后病理等级分布,分析二次手术情况、首次手术切缘阳性率、残留率、复发率及1年内HPV转阴率和持续感染率。结果在宫颈HSIL的诊断上,CKC术后病理与活检病理符合率为72.52%(256/353),具有一致性(P 0.0001);LEEP术后病理与活检病理符合率为58.86%(103/175)(P 0.0001);CKC术后切缘阳性率为7.41%(20/270),残留和复发率为5.93%(16/270),LEEP术后切缘阳性率为5.66%(6/106),残留和复发率为4.71%(5/106);CKC和LEEP术后1年内HPV转阴率分别为69.80%(104/149)和56.06%(37/66),1年随访高危HPV持续感染率均降低。结论 CKC术和LEEP术对宫颈HSIL的诊断均具有一致性,随访1年内HPV转阴率均较高,需根据多因素综合分析制定个体化手术方案。     

Colposcopy vs Hybrid Capture II assay in detection of cervical human papilloma virus infection

PURPOSE OF INVESTIGATION: Considering the relationship between high-risk human papillomavirus types and the presence or subsequent development of cervical high-grade preinvasive lesions, the aim of the study was to determine if the Hybrid Capture II test can be used to triage women with atypical colposcopic findings. METHODS: The study was carried out on 100 patients with suspicious colposcopy findings (suggestive of human papillomavirus infection) who underwent a cervical smear for human papillomavirus testing DNA Hybrid Capture II and direct biopsies for histopathological analysis. RESULTS: Sixteen patients were negative for human papillomavirus. Of the eight patients positive for high-risk HPV type, seven presented an abnormal transformation zone grade 2 (high-grade squamous intraepithelial lesion of the cervix at histopathology). There was a significant positivity of medium-high risk virus types in the cases with more abnormal colposcopy (chi2 = 7.44; p < 0.005). Histopathological findings of high-grade squamous intraepithelial lesions were registered in the patients positive for medium-high risk human papillomavirus types (chi2 = 7.66; p < 0.025). CONCLUSIONS: Based on these results it can be concluded that if a diagnosis of a high-grade squamous intraepithelial lesion has been made on the basis of colposcopic and histopathological findings, there is a high probability that the infection was due to one or more types of human papillomavirus. There are necessary further studies to interpretate both the advantages and disadvantages of intermediate triage procedures, like Hybrid Capture II testing, compared with immediate colposcopy.     

Human papillomavirus–specific viral types are common in Mexican women affected by cervical lesions

Cervical cancer (CC) is the most common in Mexican female population. The human papillomavirus (HPV) 16 and 18 frequencies in worldwide may be different due to geographical distribution. We analyzed the prevalence of HPV types and determinated their association in cervical lesion in a Mexican population. One hundred fifty-nine normal cervical smears, 95 low-grade squamous intraepithelial lesions (LGSIL), 59 high-grade squamous intraepithelial lesions (HGSIL), and 108 CC samples of the patients were collected. HPV types were determined by sequencing. We detected 11 high-risk types, four low-risk types, three not determinated, and two probably high risk. HPV were present in 12%, 57%, 88%, and 92% from normal, LGSIL, HGSIL, and CC samples, respectively. HPV 16 was the most common in all cervical lesions (71.6% in CC). HPV 58 was present in 18.6% of HGSIL, and the HPV 18 in 4.6% of CC. The 76% of all detected viruses belong to A9 species branch. Control women showed high percentage of HPV high-risk infection, suggesting that this is a high-risk group. High frequency of HPV 16 compared with a low incidence of HPV 18 was observed. HPV 58 is frequently detected in HGSIL but low frequency is found in CC. These findings might be considered for HPV screening.