阴道镜联合HPV检测对宫颈癌及宫颈上皮内瘤变的诊断价值

目的探讨阴道镜联合高危型人乳头瘤病毒(HR-HPV)检测对宫颈癌及宫颈上皮内瘤变的诊断价值。方法对644例行宫颈癌筛查的妇女行阴道镜和HR-HPV检测,并应用阴道镜取宫颈多点活组织进行病理检查。结果HR-HPV诊断结果阳性率为17.70%,阴道镜诊断结果阳性率为18.01%,HR-HPV+阴道镜诊断结果阳性率为18.79%;HR-HPV+阴道镜检测灵敏度和符合率与单一使用阴道镜或HR-HPV检测比较,P<0.05,差异具有统计学意义;HRHPV检测低危病变阳性率和高危病变阳性率比较,P<0.05,差异具有统计学意义。结论阴道镜联合HR-HPV检测可提高宫颈癌及宫颈上皮内瘤变的诊断灵敏度和符合率,高危病变HR-HPV检测阳性率更高。     

液基细胞学与HPV分型联合检测对早期宫颈癌的筛查意义

目的探讨液基细胞学(TCT)联合人乳头瘤病毒(HPV)分型检测对早期宫颈癌筛查的临床意义。方法选择慢性宫颈炎患者714例。TCT采用离心甩片法,HPV-DNA检测采用PCR-反向点杂交法,对TCT和HPV-DNA任一检测阳性或二者均阳性者进行阴道镜取活检检查。结果在HPV感染的各年龄组中,20~30岁组和51~60岁组的感染率较高,分别为36.7%和39.7%,各年龄组感染率差异有统计学意义(χ~2=14.974,P=0.039)。TCT检测的阳性率为25.8%,HPV-DNA检测的阳性率为29.7%,略高于TCT检测,但差异无统计学意义(P<0.05)。HPV-DNA高危型感染者中病理诊断为宫颈癌5例,占6.5%,高于HPV-DNA低危型感染者宫颈癌的发生率(0.7%),差异有统计学意义(P<0.05)。TCT联合HPV-DNA分型检测诊断宫颈癌的敏感度高于TCT和HPV-DNA单独检测,特异度高于HPV-DNA单独检测,假阳性率低于HPV-DNA单独检测,假阴性率低于TCT和HPV-DNA单独检测,差异有统计学意义(P<0.05)。结论TCT联合HPV-DNA分型检测可以提高诊断宫颈癌的敏感性和特异性,对宫颈癌的早发现、早治疗有重要临床意义。     

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.     

310例宫颈上皮内瘤变(CIN)术后随访的临床分析

目的:分析310例CIN术后随访资料。方法:比较手术前后3月、6月、12月液基细胞术(TCT)阳性率、HPV感染率的改变。分析其与不同年龄,不同病变程度间的关系。结果:310例标本中,术后3月TCT阳性率由术前89.68%降至30.00%,术后6月、12月TCT的阳性率分别为6.77%、1.61%;术后3月HPV的感染率由术前93.55%降至56.77%,术后6月、12月分别为14.19%、5.48%。随年龄增加,术后3月、6月,不同年龄组TCT阳性率及HPV感染率分别逐渐增加,且各组间的差异分别具有显著性(P<0.05)。术后12月,51-60岁年龄组TCT阳性率及HPV感染率均显著高于其余各组,差异具有显著性(P<0.05),而其它各组间差异无显著性(P>0.05);随CIN级别增加,术后3月、6月、12月TCT的阳性率及HPV的感染率分别增加,在同一随访时限内不同级别间TCT阳性率及HPV感染率差异分别具有显著性(P<0.05)。结论:宫颈环形电切术(LEEP)能显著减低TCT、HPV的阳性率。术后3月复查HPV阳性率下降不明显,术后6月HPV阳性率明显降低。对于年龄较大、病变程度高的CIN术后患者,应加强随访。     

液基细胞学筛查宫颈癌的研究

目的 评价ThinPrep液基细胞学在宫颈癌高发区筛查的准确性。方法 1997年例受检者同时做宫颈脱落细胞液基标本采集和阴道镜活检,用液基标本做薄片细胞学诊断和肿瘤相关人乳头瘤病毒（human papilloma virus,HPV)检测。细胞学诊断采用TBS分级系统,阳性诊断包括意义不明的不典型鳞状细胞（ASCUS）以上病变,诊断结果与阴道活检诊断和肿瘤相关HPV DNA阳性检出率对照。所有检查均双盲进行。结果 ThinPrep液基细胞学检出100％（12／12）的鳞状细胞癌（SCC）;93．2％（69／74）的鳞状上皮内高度病变（HSIL）,其中CIN396．8％（30／31）,CIN90．7％（39／43）;72．4％（92／127）的鳞状上皮内低度病变（LSIL）。SCC和CIN3的分级准确率分别达100％和87．1％。HPVDNA阳性检出率与细胞学分级密切相关,且在细胞学与组织学相同级别基本一致。结论 宫颈液基标本收集方法有利于细胞学和肿瘤相关HPV DNA双重检查。ThinPrep液基细胞学检查敏感性高,尤其是对鳞状上皮内高度病变。     

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。     

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。     

HPV E6/E7 mRNA和HPV DNA检测技术在宫颈上皮内瘤变中的诊断价值分析

目的比较人乳头瘤病毒(HPV)E6/E7 mRNA和HPV DNA检测技术对宫颈上皮内瘤变(CIN)2级及以上(CIN2+)患者的诊断价值,并评价HPV E6/E7 mRNA检测结果在不同实验室间的一致性。方法采用HPV E6/E7 mRNA和HPV DNA检测技术对212例门诊体检的健康者和住院的宫颈病变患者的宫颈脱落细胞学标本进行检测。以病理诊断结果为金标准,评价两种检测技术诊断CIN2+的灵敏度和特异度。北京市迪安中心实验室和北京市怀柔妇幼保健院实验室均采用HPV E6/E7 m RNA检测技术检测同一批标本,评价实验室间检测的一致性。结果HPV E6/E7 m RNA检测的阳性率为38.7%,与HPV DNA的阳性率43.9%比较,差异无统计学意义(P﹥0.05)。HPV E6/E7 mRNA和HPV DNA的检测阳性率均随着病理分级的升高而增加(P<0.01)。HPV E6/E7mRNA检测CIN2+的灵敏度为92.96%,与HPV DNA的90.14%相比,差异无统计学意义(P﹥0.05),而HPV E6/E7mRNA检测CIN2+的特异度为88.65%,高于HPV DNA的79.43%,差异有统计学意义(P<0.05)。两个实验室采用HPV E6/E7 m RNA检测阳性一致的标本例数为78,阴性一致的标本例数为121,总一致率为93.87%,Kappa=0.872,一致性较好。结论与HPV DNA检测技术相比,HPV E6/E7 mRNA检测宫颈病变的特异度更具优势,实验室间重复性检测的一致率较高,有望成为中国宫颈癌HPV筛查的首选方法。     

液基薄层细胞学检测联合高危型人乳头瘤病毒检测对宫颈癌前病变的诊断价值探讨

目的 本研究旨在探讨液基薄层细胞学(LCT)检测联合高危型人乳头瘤病毒(HR-HPV)检测对宫颈癌前病变的诊断价值.方法 对门诊进行宫颈癌筛查的4009例患者的宫颈脱落细胞采用LCT联合HR-HPV基因分型,然后与宫颈组织病理学诊断结果进行比较分析,探讨这两种宫颈癌筛查方法的灵敏度和特异度.结果低于21岁的女性受试者的HPV、LCT以及两者联合检测的阳性率明显高于21~29岁、30~65岁、﹥65岁的女性受试者.本研究2716例30~65岁女性人群中,宫颈组织病理学异常者158例,其中HR-HPV阳性者占81.6%(129/158);宫颈细胞学异常者占55.7%(88/158);LCT联合HR-HPV阳性者占88.0%(139/158).LCT联合HR-HPV检测的灵敏度和特异度高于单独的LCT检测或者HR-HPV检测.结论 在宫颈癌筛查中,LCT联合HR-HPV检测的灵敏度和特异度高于单独的LCT检测或者HR-HPV检测,可发现LCT或者HR-HPV漏诊的宫颈组织病变,从而降低癌前病变及宫颈癌的发生率和死亡率,值得在临床大力推广应用.     

Nitrative and oxidative DNA damage in cervical intraepithelial neoplasia associated with human papilloma virus infection

Recently, it was proposed that inflammation plays an integral role in the development of human papilloma virus (HPV)-induced cervical cancer. The present study sought to examine if 8-nitroguanine, a mutagenic nitrative DNA lesion formed during inflammation, contributes to cervical carcinogenesis. We obtained biopsy specimens from 30 patients with cervical intraepithelial neoplasia (CIN)1 (n = 9), CIN2 (n = 10), CIN3 (n = 6) and condyloma acuminatum (n = 5). We used immunohistochemistry to detect the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, and compared it with the expression of the cyclin-dependent kinase inhibitor p16, which is considered to be a biomarker for cervical neoplasia. Double immunofluorescence labeling revealed that 8-nitroguanine and 8-oxodG were colocalized in cervical epithelial cells. Samples from CIN2-3 patients, most of whom were infected with high-risk HPV subtypes, exhibited significantly more intense staining for 8-nitroguanine than those with condyloma acuminatum. 8-Nitroguanine and 8-oxodG immunoreactivities correlated significantly with the CIN grade. We observed the expression of inducible nitric oxide synthase in epithelial and inflammatory cells from CIN lesions. Proliferating cell nuclear antigen was expressed specifically in dysplastic epithelial cells, but not in those of condyloma acuminatum. There were no statistically significant differences in p16 expression between CIN and condyloma acuminatum samples. These results suggest that high-risk HPV types promote inducible nitric oxide synthase-dependent DNA damage, which leads to dysplastic changes and carcinogenesis; in contrast, p16 appears to be merely a marker of HPV infection. Thus, 8-nitroguanine is a more suitable and promising biomarker for evaluating the risk of inflammation-mediated cervical carcinogenesis than p16.     

Cervical intraepithelial neoplasia and human papilloma virus infection.

Evidence of human papilloma virus (HPV) infection was sought in 50 patients with cervical intraepithelial neoplasia (CIN) and 50 controls. Cytologic, colposcopic and histopathological examinations were carried out in each one of them. Cytological evidence of HPV infection was found in 13 cases and two controls. Colposcopic evidence was found in 33 (66%) cases and 17 (34%) controls and histopathological evidence in 35 (70%) patients and 14 (28%) controls. These differences were statistically significant. Colposcopy proved to be a good method of diagnosing HPV infection with a sensitivity of 86% and specificity of 80% compared to histopathologic diagnosis.     

Cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant recipients

An association between human papilloma virus (HPV) infection and cervical intraepithelial neoplasia has been well established Renal transplant recipients on long term immunosuppression are prone to viral infection. It is possible that there may be an increased prevalence of papilloma virus infection and associated cervical intraepithelial neoplasia in these women. Prospective study of 42 renal transplant recipients and 41 age and parity matched controls was undertaken to determine whether HPV infection and cervical intraepithelial neoplasia (CIN) occurred more often in renal allograft recipients and to assess the relative risk. All women underwent Pap smear, colposcopy, histological examination of biopsy specimen and polymerase chain reaction for HPV 16. Cytology did not pick up HPV infection in any of the women. Colposcopy revealed HPV infection in 15 and CIN in 14 women in the immunosuppressed group and HPV in 7 and CIN in 5 women in control group. Histological evidence of HPV was found in 24 and CIN in 10 women in immunosuppressed group and HPV infection in 13 and CIN in 3 women in control group, giving an odds ratio of 6.1. More women in the immunosuppressed group had CIN of higher degree as well. PCR revealed infection by HPV 16 in 17 cases and 14 controls giving an odds ratio of 1.3. Therefore renal allograft recipients on immunosuppression should be screened by colposcopy and directed biopsy at regular intervals.     

High-risk human papilloma virus and cervical abnormalities in HIV-infected women with normal cervical cytology

Background

The prevalence of High-Risk Human papilloma virus (HR-HPV), a necessary cause of invasive cervical cancer (ICC) is relatively high in HIV infected women. Gaps exist in our knowledge of the optimal approaches for managing women who have HR-HPV with normal cervical cytology (NCC) particularly in settings of HIV infection.

Methods

Between May 2012 and June 2013 we conducted a colposcopic assessment of HIV-infected women with prior (NCC) and known HR-HPV status to compare cervical abnormalities in women with and without HR-HPV. Colposcopic examinations were done at the Operation Stop Cervical Cancer (OSCC) unit of the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Abnormal colposcopic finding (ACF) was defined as areas of aceto-white epithelium involving the squamo-coulumnar junction, areas of punctation, mosaic pattern or atypical vessels. We compared proportions of ACF as well as histologic grades of cervical intra-epithelial neoplasia (CIN) in women with or without HR-HPV. Statistical analysis was done on STATA.

Results

We conducted colposcopic examinations in 78 out of 89 (86.5%) eligible women. The mean age of the cohort was 32.4 years (SD ±4.6) with a median 32 years (IQR 29–36). After a mean follow up time of 20.1 months from the initial cervical pap cytology and HR-HPV testing, we found 12 of 78 (15.4%) women with ACF. The odds for an ACF was statistically higher [OR = 4.0 (95% CI: 1.1-14.7)] in women with HR-HPV compared to those without. Of the twelve women with ACF, subsequent histologic examination of colposcopically directed cervical biopsies confirmed CIN 1 in 4 cases (33.3%), CIN 2 in 1 case (8.3%), CIN 3 in 2 cases (16.7%), carcinoma-in-situ (CIS) in 2 cases (16.7%), and normal cervix in 3 (25.0%). Overall, the proportion of women detected with any grade of CIN was 11.5% (9/78) and 6.4% (5/78) were CIN 2 or greater lesion (CIN2+).

Conclusion

HIV-infected women with NCC and HR-HPV had a four-fold higher likelihood for an ACF. The practice of early colposcopic examination of HIV-infected women with prior NCC and HR-HPV may increase early detection of higher grade CIN and CIS cancer stages in our setting.

     

Role of high risk-human papilloma virus test in the follow-up of patients who underwent conization of the cervix for cervical intraepithelial neoplasia

Objective

To examine whether the presence of high risk-human papilloma virus (HR-HPV) after conization of the cervix was a risk factor for persistence or recurrence of cervical intraepithelial neoplasia (CIN) and whether HR-HPV test could be a guideline for post-therapy surveillance.

Methods

The study retrospectively analyzed data from 243 patients who underwent LLETZ or CKC of the cervix due to CIN.

Results

A positive HR-HPV test result which was performed between 3 and 6 months after procedure was a risk factor for persistent or recurrent cytological (p<0.001, odds ratio [OR]=22.51, 95% confidence interval [CI]=9.74-52.02) and pathological (p<0.001, OR=18.28, 95% CI=5.55-60.20) abnormalities.

Conclusion

HR-HPV positive patients between 3 and 6 months after procedure should undergo frequent and meticulous post-therapy surveillance, while HR-HPV negative patients do not require such high-level surveillance and could undergo routine surveillance.     

宫颈癌放疗后液基薄层细胞学检测分析

目的分析宫颈癌放疗后宫颈细胞学改变特点及该项检测的临床意义。方法196例宫颈癌放疗后患者放疗结束1个月后行489次宫颈液基薄层细胞学检查(LCT)。采用2001年版TBS诊断系统,对细胞改变作描述性诊断。结果在放疗结束1年内,鳞状上皮表层细胞体积增大不明显、核可增大,但较疏松、胞浆丰富,可出现空泡。部分涂片上可见退变的癌细胞,部分病例见修复细胞和化生细胞。异常鳞状上皮细胞检出率为40.3%,其中不典型鳞状细胞(ASCUS)、低度鳞状上皮内病变(LSIL)、高度鳞状上皮内病变(HSIL)分别为20.1%,5.3%、10.8%。鳞癌(SCC)检出率为3.1%。炎症反应性细胞检出率为42.5%,其中轻、中、重度分别为6.3%,19.4%,16.8%。35例放疗后因细胞学检查异常进行了局部病理组织学检查,病理与LCT两者符合率为91%。结论宫颈液基薄层细胞学可作为宫颈癌放疗后局部有无复发及放射反应的监测指标。     

宫颈脱落细胞检查联合人乳头瘤病毒检测对诊断宫颈癌的临床意义

目的探讨宫颈脱落液基细胞学检查(TCT)联合人乳头瘤病毒检测(HPV-DNA)诊断宫颈癌的临床意义。方法选取2012年5月至2015年5月间海南省文昌市人民医院收治的100例宫颈癌患者,分别单独行TCT检测、单独HPV-DNA检测、HPV-DNA+TCT检测,比较3种检测方法的诊断结果。结果 HPV-DNA+TCT检测宫颈癌的阳性率为81.0%,显著高于单独TCT检测的51.0%和单独HPV-DNA检测的55.0%,差异有统计学意义(P<0.05);单独TCT与单独HPV-DNA检测的阳性率间差异无统计学意义(P>0.05)。结论 TCT和HPV-DNA联合诊断宫颈癌阳性符合率较高,具有显著的临床应用价值。     

Photodynamic therapy for cervical intraepithelial neoplasia

OBJECTIVES: Photodynamic therapy (PDT) is a minimally invasive treatment for cervical intraepithelial neoplasia (CIN). We report the effectiveness of PDT in 105 cases of CIN. METHODS: All patients received photofrin (PHE) 2 mg/kg intravenously and, 48-60 h later, phototherapy was performed using the Excimer dye laser or a YAG-OPO laser with an irradiation dose of 100 J/cm(2) using 630 nm wavelength. RESULTS: Mild photosensitivity occurred in 48% (50/105) of patients. The complete response (CR) rate was 90% (94/105) at 3 months following treatment. In the remaining 11 patients, 5 patients had CIN1, 2 patients had CIN2, and 4 patients had mild cytologic findings. However, in 9 of these 11 patients, CR was achieved 6 months after PDT. In 69 patients, human papilloma virus (HPV) typing was performed before and after PDT therapy. Pre-treatment, 64 of 69 patients (93%), were HPV-positive including 30 cases of high-risk HPV (43%). Testing performed 3, 6 and 12 months following PDT revealed no HPV-DNA in 75% (52/69), 74% (48/65) and 72% (41/57) of patients. At present, the median follow-up period is 636 days (90-2,232 days). In 3 patients, recurrence requiring surgical treatment was identified at 646, 717 and 895 days after PDT. CONCLUSIONS: PDT is an effective and minimally invasive treatment for CIN, which also appears to eradicate HPV infection.