宫颈上皮内瘤变相关影响因素病例对照研究

目的 宫颈癌是全球范围内高发于女性的恶性肿瘤,宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)是其癌前病变.本研究旨在探讨CIN的相关影响因素,分析高危型人乳头瘤病毒(high-risk human papillomavirus,HR-HPV)及沙眼衣原体(chlamydia trachomatis,CT)感染与CIN的相关性.方法 选择2010-01-01-2014-04-30柳州市人民医院门诊就诊的女性患者,共纳入符合筛查条件的患者12 644例,行宫颈脱落细胞CT和HR-HPV-PCR检测,以及液基薄层细胞学检查,必要时宫颈活组织检查.记录CT及HR-HPV不同感染状态发生CIN的情况,应用SPSS17.0软件包进行非参数检验和多因素Logistic回归分析.结果 12 644例患者中,检查出CIN 260例,检出率为2.06％.HR-HPV(OR=18.516)、CT感染(OR=2.602)、妊娠次数增加(OR=1.477)和年龄(OR=1.690)与CIN发生相对危险度增加.以HR-HPV和CT不同感染状态进行分层,CIN在不同HR-HPV及CT感染状态组别中发生率不同,HR-HPV和CT均阳性组最高(18.00％),其次依次为HR-HPV阳性组(10.26％)、CT阳性组(1.97％)、HR-HPV和CT均阴性组(0.49％),差异均有统计学意义,x2 =875.927,P＜0.001.结论 年龄与孕次增加是CIN发生的相关影响因素,HR-HPV与CIN发生密切相关,宫颈CT感染亦与CIN发生相关,CT与HR-HPV协同可能增加CIN发生.     

派特灵治疗宫颈上皮内瘤变Ⅰ、Ⅱ期临床疗效

目的观察派特灵治疗宫颈上皮内瘤变(CIN)的疗效。方法将病理确诊的CINⅠ、Ⅱ期患者分为2组,观察组63例应用派特灵进行治疗;对照组60例采用外用干扰素。结果观察组CINⅠ、Ⅱ期治疗有效率为98.4%,高于对照组的60.0%,差异有统计学意义(P<0.05);观察组宫颈高危HPV感染治疗有效率为96.7%,高于对照组的67.9%,差异有统计学意义(P<0.05)。结论应用派特灵治疗CIN I、Ⅱ期合并HPV高危感染患者有效,在临床上有推广价值。     

宫颈电环切除术治疗宫颈上皮内瘤变136例

[目的]观察宫颈电环切除术（LEEP）治疗宫颈上皮内瘤变（CIN）的疗效。[方法]对136例CIN患者行LEEP治疗，对其疗效作回顾性分析。[结果]术前术后病理诊断一致占39．71％（54／136）；术后病理诊断级别下降占44．12％（60／136），其中下降一级占24.26％，下降两级占19．12％，下降三级占0．74％：术后病理诊断级别上升占16．18％（22／136），其中上升一级占13．24％，上升两级占2．94％。手术切缘阳性5例。术后半年无CIN占132例，治愈率为97．06％。[结论]LEEP治疗CIN安全有效、简单易行、并发症少，能保留患者的生育功能，在治疗的同时能进行诊断．但术后需定期和规范的随访。     

宫颈电圈切除术对重度宫颈上皮内瘤变的诊疗价值及高危型HPV检测的临床意义

目的探讨宫颈电圈切除术(LEEP)对重度宫颈上皮内瘤变(CINⅡ～Ⅲ)的诊疗价值,研究高危型人乳头瘤病毒(HPV)在重度CIN中的感染情况及对LEEP术预后的影响.方法对112例重度CIN患者行阴道镜活检及LEEP术治疗,并同时行高危型HPV的PCR检测,对其疗效及预后进行分析.结果在112例重度CIN患者中,CIN Ⅱ级67例,CIN Ⅲ级(包括原位癌)45例.LEEP术后随访,治愈98例,治愈率达87.5%;发现病变残留者14例(12.5%),复发者4例(3.6%).在所有患者中,92例高危型HPV检测阳性,总感染率为82.1%.CIN Ⅲ级患者HPV阳性率(93.3%)较CIN Ⅱ级患者(74.6%)显著升高(P<0.05).高危型HPV阳性组LEEP术后病变残留率或复发率与HPV阴性组比较,差异无显著性(10.9%比20.0%,或4.3%比0;P>0.05).因CIN残留或复发而再次行LEEP术的13例患者中,检测到12例(92.3%)仍有高危型HPV感染.结论 LEEP术是诊断和治疗重度CIN的有效且理想的方法.高危型HPV与重度CIN的发生有关.术前高危型HPV阳性与否似乎与LEEP术预后无关.     

珠海地区妇女宫颈上皮内瘤变与高危型人乳头瘤病毒亚型关系的初步研究

目的探讨珠海地区妇女宫颈上皮内瘤变与高危型人乳头瘤病毒亚型的关系。方法采用杂交捕获二代（HC-Ⅱ）方法定量检测珠海地区宫颈疾病患者HPV-DNA的含量,全部269例患者阴道镜下多点取活组织病理检查,根据病理学诊断结果分组。结果珠海地区高危型HPV在慢性宫颈炎、C INⅠ、C INⅡ及C INⅢ的感染率分别为13.5%、48.2%、73.8%及93.7%,HPV16在四组中感染率依次为3.6%、13.4%、47.6%及65.6%,宫颈病变存在多重HPV感染。结论珠海地区宫颈上皮内瘤变患者感染HPV16、18、31、58及35型较多见,多重HPV感染可能促进宫颈上皮内瘤变的发生。     

宫颈电环切除术治疗宫颈上皮内瘤变136例

[目的]观察宫颈电环切除术（LEEP）治疗宫颈上皮内瘤变（CIN）的疗效。[方法]对136例CIN患者行LEEP治疗，对其疗效作回顾性分析。[结果]术前术后病理诊断一致占39．71％（54／136）；术后病理诊断级别下降占44．12％（60／136），其中下降一级占24.26％，下降两级占19．12％，下降三级占0．74％：术后病理诊断级别上升占16．18％（22／136），其中上升一级占13．24％，上升两级占2．94％。手术切缘阳性5例。术后半年无CIN占132例，治愈率为97．06％。[结论]LEEP治疗CIN安全有效、简单易行、并发症少，能保留患者的生育功能，在治疗的同时能进行诊断．但术后需定期和规范的随访。     

宫颈上皮内瘤变患者高危型HPV基因分型的研究

[目的]研究青岛地区宫颈上皮内瘤变患者的高危型人乳头瘤病毒感染的基因分型情况。[方法]应用型特异聚合酶链反应检测宫颈上皮内瘤变患者高危型HPV的分型情况。[结果]各型HPV的感染率之间差异具有非常显著性（χ^2=42.632,P〈0.001）。四种高危型HPV感染率从高到低依次为：HPV16,HPV58,HPV18,HPV33。[结论]青岛地区主要高危型HPV在宫颈上皮内瘤变患者中感染的主要型别依次为HPV16,HPV58,HPV18,HPV33,为宫颈疾病的筛查和治疗提供依据,同时也指导本地区HPV疫苗的研究。     

宫颈上皮内瘤变150例临床分析

目的：探讨宫颈上皮内瘤变（CIN）的诊断及治疗方法。方法：回顾分析1984年1月至1998年12月住院治疗的150例CIN的临床资料。结果宫颈细胞学检查诊断的阳性率为76．65,与宫颈管细胞学检查联合应用诊断的阳性率为78．8％,两者比较无显著性差异。细胞检查结合阴道镜下活检诊断CIN阳性率为95．3％,与单一细胞学诊断相比较,有显著性差异。阴道镜下活检与病理诊断的符合率为91．6％,镜下活检与宫颈管刮术结合诊断的阳性率明显高于单纯阴道镜下活检。141例采用手术治疗,无1例切缘阳性;9例原位癌采用腔内放疗,全组无1例复发或死亡。结论宫颈细胞学检查结合阴道镜检是诊断CIN的有效方法,对绝经后妇女应同时行宫颈管刮术,对不宜手术的原位癌患者可行单纯腔内放疗。     

Predictors of Absent High-grade Cervical Intraepithelial Neoplasia (CIN) in Loop Electrosurgical Excision Procedure Specimens of Patients with Colposcopic Directed Biopsy-Confirmed High-Grade CIN

Objective: To determine predictors of having cervical intraepithelial neoplasia (CIN) 1 or less in loopelectrosurgical excision procedure (LEEP) specimens of patients with colposcopic directed biopsy-confirmed CIN 2-3.Methods: Two hundred and eighty patients with colposcopic directed biopsy-confirmed CIN 2-3 who subsequentlyunderwent LEEP were enrolled in the retrospective study. Related clinical data were collected to determine the predictors ofCIN 1 or less in LEEP specimens. Results: CIN 1 or less in LEEP specimens was found in 71 (25.4%) of 280 patients.Multivariate logistic regression analyses demonstrated that nulliparity [OR (95% CI) = 3.375 (1.245-9.150)], lowgrade Papanicolaou (Pap) results [OR (95% CI) = 6.410 (2.877-14.280)] and low grade colposcopic impression[OR (95% CI) = 16.506 (5.844-46.632)] were significant risk factors of having CIN 1 or less in LEEP specimens. Neitherpersistent nor recurrent CIN 2-3 was detected in 71 patients who had CIN 1 or less in LEEP specimens. However,persistent or recurrent CIN 2-3 developed in 3 out of 209 (1.4%) patients with CIN 2-3 found in LEEP specimens.Conclusion: Approximately 25% of patients with CIN 2-3 in colposcopic directed biopsy specimens had CIN 1 or lessfound in LEEP specimens. Predicting factors of having CIN 1 or less in LEEP specimens were nulliparity, low gradePap results and low grade colposcopic impression.     

Long-term Outcomes of a Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia in a High Incidence Country

Aim: To evaluate the operative, oncologic and obstetric outcomes of the loop electrosurgical excision procedure(LEEP) in cases with cervical neoplasia. Materials and Methods: A retrospective cohort study was conducted onpatients who were suspected of cervical neoplasia and therefore undergoing LEEP at Siriraj Hospital, MahidolUniversity, Thailand, during 1995-2000. Outcome measures included operative complications in 407 LEEPpatients and long-term outcomes in the 248 patients with cervical intraepithelial neoplasia (CIN) who weretreated with only LEEP. Results: There were 407 patients undergoing LEEP; their mean age was 39.7±10.5years. The histopathology of LEEP specimens revealed that 89 patients (21.9%) had lesions ≤CIN I, 295 patients(72.5%) had CIN II or III, and 23 patients (5.6%) had invasive lesions. Operative complications were found in15 patients and included bleeding (n=9), and infection (n=7). After diagnostic LEEP, 133 patients underwenthysterectomy as the definite treatment for cervical neoplasia. Of 248 CIN patients who had LEEP only, seven(2.8%) had suffered recurrence after a median of 16 (range 6-93) months; one had CIN I, one had CIN II, andfive had CIN III. All of these recurrent patients achieved remission on surgical treatment with re-LEEP (n=6) orsimple hysterectomy (n=1). A significant factor affecting recurrent disease was the LEEP margin involved withthe lesion (p=0.05). Kaplan-Meier analysis showed 5-year and 10-year disease-free survival (DFS) estimates of99.9%. Twelve patients became pregnant a total of 14 times, resulting in 12 term deliveries and two miscarriages- one of which was due to an incompetent cervix. Conclusions: LEEP for patients with cervical neoplasia deliversfavorable surgical, oncologic and obstetric outcomes.     

Distribution of HPV-16 Intratypic Variants among Women with Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer in Mongolia

Objectives. Infection with high-risk human papillomavirus (HPV) is a critical factor associated withcarcinogenesis of the uterine cervix. HPV-16 is most frequently found, and is further subclassified into intratypicvariants based on the nucleotide sequences of the viral genes. Although certain HPV-16 variants are reported tobe associated with the progression of cervical lesions, these relationships remain controversial with differentresults for different populations. To provide data for another population, we investigated the prevalence ofHPV-16 and distributions of its intratypic variants among Mongolian women with cervical intraepithelialneoplasia (CIN) and invasive cervical cancer. Materials and Methods. We analyzed samples from 374 randomlyselected women who attended the National Cancer Center of Mongolia between January 2002 and July 2007,including 147 invasive cervical cancer patients, 127 CIN patients and 100 age-matched controls who werecytologically normal. HPV genotyping was initially conducted, followed by variant analysis for HPV-16-positivesamples by nucleotide sequencing of the E6 gene. The HPV data were evaluated statistically for correlationswith the patients’ clinical data. Results. HPV genotyping detected 101 HPV-16-positive samples. Among thesesamples, 92 were available for subsequent variant analysis, including 66 invasive cervical cancer samples, 25CIN samples and 1 cytologically normal sample. A total of 14 different variants were identified. All 14 variantsbelonged to the European lineage, and the European prototype was detected in 66% (61/92) of the samples.Among the remaining 31 variants, variants with the T350G nucleotide change were predominant (13/31, 42%),followed by variants containing G94A (11/31, 35%), G176A (4/31, 13%) and G274T (2/31, 7%) . There were nosignificant differences among all the variants regarding their distributions in CIN and invasive cervical cancers.Conclusions. HPV-16 variants of the European lineage were exclusively distributed among the Mongolian womenexamined, and the European prototype was overwhelmingly predominant. Since no significant differences werefound between the types of variants and severities of the cervical lesions, it is possible that racial or geographicfactors may have some influences on these relationships.     

宫颈上皮内瘤变管理的进展

宫颈上皮内瘤变（CIN）是一组宫颈癌的癌前病变,它能反应宫颈癌发生发展的连续过程。宫颈癌早诊早治工作的广泛开展,使其预防和治疗关口明显前移。因此,如何规范CIN的管理已成为宫颈癌防治工作的关键。该文针对CIN各级的特性及其管理的新进展进行综述。     

Human Papillomavirus Genotype Distribution among Thai Women with High-Grade Cervical Intraepithelial Lesions and Invasive Cervical Cancer: a Literature Review

Infection with high-risk human papillomavirus (HR-HPV) is an essential cause of cervical cancer. Becauseof substantial geographical variation in the HPV genotype distribution, data regarding HPV type-specificprevalence for a particular country are mandatory for providing baseline information to estimate effectivenessof currently implemented HPV-based cervical cancer prevention. Accordingly, this review was conducted toevaluate the HR-HPV genotype distribution among Thai women with precancerous cervical lesions i.e. cervicalintraepithelial neoplasia grade 2-3 (CIN 2-3), adenocarcinoma in situ (AIS), and invasive cervical cancer byreviewing the available literature. The prevalence of HR-HPV infection among Thai women with CIN 2-3 rangedfrom 64.8% to 90.1% and the three most common genotypes were HPV 16 (38.5%), HPV 58 (20.0%), and HPV18 (5.5%). There were high squamous cell carcinoma/CIN 2-3 prevalence ratios in women with CIN 2-3 infectedwith HPV 33 and HPV 58 (1.40 and 1.38, respectively), emphasizing the importance of these subtypes in the riskof progression to invasive cancer among Thai women. Data regarding the prevalence and genotype distributionof HR-HPV in Thai women with AIS remain unavailable. Interesting findings about the distribution of HPVgenotype in cervical cancer among Thai women include: (1) a relatively high prevalence of HPV 52 and HPV58 in invasive squamous cell carcinoma; (2) the prevalence of HPV 18-related adenocarcinoma is almost doublethepreviously reported prevalence, and (3) 75% of neuroendocrine carcinomas are HPV18-positive when takinginto account both single and multiple infections.     

海岛妇女LEEP治疗高级别宫颈上皮内瘤变168例临床分析

目的：探讨宫颈上皮内瘤样病变（CIN）Ⅱ～Ⅲ宫颈环形电刀切除术（LEEP）治疗的有效性。方法：回顾分析浙江省舟山市妇幼保健院2002年6月至2007年9月因CINⅡ～Ⅲ行LEEP手术的168例患者临床资料，对手术前后病理、术后患者的治愈率、病变持续存在及复发等情况进行分析总结。结果：手术前后病理诊断符合率64.3%（108/168），升级占12.5%（21/168），降级占23.2%（39/168）。剔除LEEP术后切缘阳性或宫颈癌再次手术者19例，接受6～69个月随访者149例，总治愈率96.0%（143/149），病变持续存在率4.0%（6/149），复发率12.1%（18/149）。LEEP术后CINⅡ41例，6个月治愈率95.1%（39/41），病变持续存在率4.9%（2/41），1年复发率为7.3%（3/41），2年复发率为7.3%（3/41）；CINⅢ81例，6个月治愈率95.1%（77/81），病变持续存在率4.9%（4/81），1年复发率为6.2%（5/81），2年复发率为7.4%（6/81），3、4、5年均无复发。CINⅡ、CINⅢ在治愈率、病变持续存在率、复发率方面比较差异无显著性（P=0.963）。LEEP术后病理切缘阳性者、阴性者复发率分别为33.3%（3/9）、10.7%（15/140），两者比较差异无显著意义（P=0.065）；病变持续存在率分别为22.2%（2/9）、2.9%（4/140），两者比较差异有显著意义（P=0.040）。病变持续存在与术后病理切缘是否受累有关，与病变级别无关。结论：对于阴道镜下点状活检诊断为CINⅡ～Ⅲ适宜行LEEP，不仅达到治疗目的，而且能进一步明确宫颈病变程度，但术后应密切随访，尤其术后前2年。     

Comparison of Cervical Levels of Interleukins-6 and -8 in Patients with and without Cervical Intraepithelial Neoplasia

Introduction: Interleukins-6 and -8 are two pro-inflammatory cytokines increasing in serum and local levels under malignant conditions. There are limited evidences on the association between cervical level of these two factors and cervical intraepithelial neoplasia (CIN). So, this study aimed to explore the association between cervical levels of IL-6 and IL-8 with cervical premalignant lesions. Methods: The present case-control study was conducted on married women undergone Pap smear for routine screening in two groups as the group with CIN (n=100) and the healthy control group (n=100). Cervical secretions were collected using sterile swab and the levels of IL-8 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The obtained data were analyzed by SPSS software. Results: The mean cervical IL-6 level was 568.66±594.62 pg/ml in the patients with CIN and 212.7±213.9 pg/ml in the controls (P <0.001). The cervical IL-8 levels in the case and control groups were measured to be 1320.43±876.5 pg/ml and 1053.59±747.64 pg/ml, respectively (p=0.02). By modifying the confounding size effect of the age and marital duration, it was determined that cervical levels of IL-6 and IL-8 were both associated with CIN. Conclusion: Our results showed that the cervical levels of IL-6 and IL-8 are associated with CIN independent of age and marital dura     

Risk Factors for High-Grade Cervical Intraepithelial Neoplasia in Patients with Atypical Squamous Cells of Undetermined Significance (ASC-US) Papanicolaou Smears

Objective: To determine risk factors of high-grade cervical intraepithelial neoplasia (CIN 2-3) among womenwith atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. Methods: Twohundredand sixty-six women with ASC-US Pap tests who underwent a colposcopy with histologic study wereenrolled between August 2008 and June 2010. Patient data including age, education, income, parity, currentpills used, number of vaginal deliveries, number of sexual partners, age at first sexual intercourse, history ofsexually transmitted diseases, history of pelvic inflammatory disease and smoking habits were obtained. Logisticregression analysis was used to evaluate factors associated with CIN 2-3. Results: CIN was diagnosed in 134 of266 women (50.4%). Ninty-seven of these (72.4%) had CIN 1 and 37 (27.6%) had CIN 2-3. Frequency of thelatter was lower in women who had at least bachelor’s degree graduation as compared to those having less thanprimary school graduation (odds ratio (OR) 0.085, 95% confidence interval (CI) 0.013-0.557). In addition, thosewith a higher income (5,000-20,000 baht per month) had less frequent CIN 2-3 (OR 0.378, 95% CI 0.147-0.970),whereas women who had 3 or more sexual partners were more likely to develop CIN 2-3 (OR 3.181, 95% CI1.316-7.687). Conclusions: Women with ASC-US Pap smears who had 3 or more sexual partners, low educationand low income were at an increased risk of CIN 2-3. Therefore, this group of patients deserve a high priorityfor immediate colposcopy in order for early detection of high-grade CIN.     

轻度宫颈上皮内瘤变自然转归的前瞻性研究

[目的]研究轻度宫颈上皮内瘤变（CINⅠ）的自然转归、人乳头瘤病毒（HPV）的自然清除率及两者之间的关系。[方法]对2003年5月到2006年4月期间,在北京大学深圳医院经阴道镜下活检病理诊断为CINⅠ的548名患者,定期随访4～6年。以宫颈液基细胞学检查（LCT）联合高危型HPV（HR-HPV）DNA检测（HC-Ⅱ）作为随访的监测方法,每6～12月随访一次。对于随访中细胞学为未明确诊断意义的不典型鳞状上皮细胞（ASCUS）及以上病变,及/或HR-HPV阳性者行阴道镜下多点活检,病理诊断。[结果]随访48个月时共失访27人,剔除34人,继续随访487人,累积未完全随访率为11.13%。随访6个月、12个月、24个月、36个月、48个月时进展为高度宫颈上皮内瘤变的百分率分别为0.55%、1.65%、3.10%、4.05%、4.11%;病变持续存在的百分率分别为70.25%、45.77%、23.79%、11.54%、7.19%;病变逆转为正常的百分率分别为29.20%、52.57%、73.11%、84.41%、88.71%。随访48个月时,35岁以上组和35岁以下组的病变进展率和逆转率均无显著性差异。随访开始时HR-HPV阳性的患者462例,随访6个月、12个月、24个月、36个月、48个月时病毒自然清除率分别为24.26%、48.69%、70.05%、81.54%、86.36%,HPV清除与CINⅠ病变逆转趋势一致。24个月内HPV持续阳性的患者,在48个月内进展为高度宫颈上皮内瘤变的比率为18.9%,显著高于HPV阴转组和HPV持续阴性组。[结论]2年内超过2/3的CINⅠ病变会自然逆转,HPV也会自然清除,但对于HPV持续阳性的患者应警惕其进展为高度宫颈上皮内瘤变。     

Comparison between Single Versus Twice Application of Topical 85% Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia; A Randomized Clinical Trial on Efficacy and Tolerability

Purpose: To compare the efficacy and safety of up to two-time administration of 85% TCA, as a promising alternative therapy to conservative and surgical management of grade one to three CINs. Methods: In this two-armed randomized clinical trial, a total of 53 patients with biopsy-proven CIN lesions were allocated to two groups of TCA treatment. The first group (n=26) received a single dose of local therapy with 85% TCA while the second group (n=27) was treated on two separate occasions with a two-week interval. Two participants (one in each group) were lost to follow-up. At the two-month follow-up after TCA application, a colposcopy-guided biopsy was performed for all patients and the pathological specimens were studied by a single experienced pathologist to determine the post-intervention grading of CIN. Results: Two groups were comparable in terms of age and base-line lesion grading, as CIN 1 lesions comprised the majority of cases (54%), followed by CIN 2(37%). While our sample was a poor representative of CIN3 lesions (7%), no significant difference was noticed between the single and twice TCA treated groups with a response rate of 52% and 54% respectively (either complete remission to normal histology or regression to any low-grade lesion). Either separate analysis (with respect to the base-line grading within each treatment group) or combined analysis (regardless of CIN sub-group) could not generate any statistical significance. The second dose of TCA did not increase the frequency of reported adverse events. Conclusion: The second dose of topical 85% TCA does not seem to increase the CIN response rate more so than its single dose. However, further controlled clinical trials with larger samples are warranted to verify current findings. The use of TCA was not limited by any major side effect, therefore, the potential to achieve an increased efficacy with more frequent TCA applications is appealing.