安康地区人乳头瘤病毒感染特征及其与宫颈癌的关系研究

目的:调查安康地区女性人乳头瘤病毒(HPV)感染的基因型别及年龄分布特征,分析其与宫颈癌的关系,为宫颈癌防治及HPV疫苗研发提供可靠的依据。方法:收集2010年6月-2012年8月间在本院及安康市部分县级医院妇产科就诊的2736名女性的液基细胞学和组织学标本,分为8个年龄组:16-24岁119例、25-29岁230例、30-34岁343例、35-39岁472例、40-44岁574例、45-49岁512例、50-54岁206例、55-86岁280例,进行病理学分类及HPV分型检测,分析不同年龄组及不同类型宫颈组织中的HPV感染率。结果:2736例女性中发生HPV感染720例(26.32%),共检出21种型别,感染率最高的基因型别是HPV16(25.05%),其他常见型别依次为HPV58、HPV52、HPV6、HPV11。单一感染占76.25%,多重感染占23.75%。HPV感染率在16-24岁、35-39岁和55-86岁三个年龄段出现高峰;而高危型HPV的感染率在35-39岁和55-86岁两个年龄段分别出现高峰。HPV的检出率随着宫颈病变的严重程度而增加,其中正常或炎症人群的HPV感染率显著低于宫颈病变及宫颈鳞状细胞癌患者(均P0.05),且意义未明的不典型鳞状细胞(ASCUS)、CIN1-3及宫颈鳞状细胞癌患者的HPV感染率对比结果存在显著差异(P0.05)。CIN1组、CIN2-CIN3组及宫颈鳞状细胞癌组单一感染率逐渐增加(P0.05),且其二重、三重感染率比较差异均有统计学意义(P0.05)。结论:安康地区HPV16型别感染较广,临床需加强对HPV16型单一感染宫颈病变患者的癌症预防工作。     

Outcomes of women with atypical squamous cells of undetermined significance and high-risk human papillomavirus DNA

OBJECTIVE: To study the risk of high-grade squamous intraepithelial lesion (HSIL) and cervical intraepithelial neoplasia (CIN) 2 or 3 in women with human papillomavirus (HPV)-positive atypical squamous cells of undetermined significance (ASCUS) cytology over a 2-year period using the 2001 Bethesda System and ThinPrep Paps. STUDY DESIGN: In 2002, 846 patients with ThinPrep cervical cytology having an ASCUS interpretation and positive for high-risk HPV DNA were identified. A cohort of 514 (60.8%) patients with follow-up by repeat cytology, cervical biopsy or both was included in the study. Patient age was 12-81 years, with a median of 25 years. RESULTS: There were 291 women (56.6%) with negative status by cytology, HPV testing or biopsy with a median interval of 8.5 months, and an additional 174 patients (33.9%) had persistent ASCUS, positive HPV DNA or low-grade SIL/CIN 1. Finally, 49 patients (9.5%) had CIN 2 or 3, with a median interval of 8.5 months. CONCLUSION: Our study suggests that HSIL or CIN 2 or 3 will be detected in 1 in 10 women with HPV-positive index ASCUS cervical cytology at initial colposcopy or within a 2-year follow-up period.     

E-cadherin 在宫颈上皮内瘤变及宫颈癌中的表达及其与高危型HPV感染的相关性

目的:研究各级宫颈上皮内瘤变(CIN)及宫颈癌组织中E-cadherin的表达及其与高危型人乳头瘤病毒(high risk human papillomavirus,HR-HPV)感染的相关性探讨其在宫颈疾病发生、发展中的意义。方法:选取2008年1月至2014年12月我院收治的150例患者标本并将其分为CINⅠ级组、CINⅡ-Ⅲ级组及宫颈癌组用免疫组化法对E-cadherin的表达情况进行检测并于术前采用PCR-反向点杂交法检测患者高危型HPV感染情况所得结果:进行统计学分析。结果:(1)E-cadherin在CINⅠ级、CINⅡ-Ⅲ级及宫颈癌中的阳性表达率分别为40/50(80.0%),24/50(48.0%)、17/50(34.0%),随疾病的进展E-cadherin的表达明显减少,各组间差异有统计学意义(P0.05)。(2)高危型HPV在CINI级、CINⅡ-Ⅲ级及宫颈癌中的阳性感染率分别为21/50(42.0%)、38/50(76.0%),48/50(96.0%),各组间差异有统计学意义(P0.05)。(3)在CIN和宫颈癌中,HR-HPV阳性组中E-cadherin阳性率39.3%(42/107)低于HR-HPV阴性组中E-cadherin阳性率90.7%(39/43)(P0.05)。结论:E-cadherin的表达下降或缺失可能是HR-HPV导致宫颈癌发生、发展的机制之一。     

A thin-layer,liquid-based pap test for mass screening in an area of China with a high incidence of cervical carcinoma. A cross-sectional,comparative study

OBJECTIVE: To confirm the accuracy of the ThinPrep Pap Test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) on the basis of histologic diagnosis by biopsy and the detection of human papillomavirus (HPV) DNA in mass screening. STUDY DESIGN: A total of 1,997 women residing in Xiangyuan County, Shanxi Province, P.R.C., an area with a high incidence of cervical carcinoma, were enrolled in this study. We collected exfoliative cervical samples from all subjects into a liquid buffer (Preserv-Cyt [Cytyc]) and utilized for both cytologic screening using the ThinPrep Pap Test and HPV DNA testing. Subsequent colposcopic biopsies were taken on all subjects. All the tests were performed in an independent and blinded fashion. We compared the ThinPrep Pap test with colposcopic biopsy and HPV test. RESULTS: High grade squamous intraepithelial lesions (HSIL) (CIN 2/3) were identified in 74 (3.7%) of 1,993 women adequately assessed, and there were 12 cases of squamous cell carcinoma (SCC). The false negative rate of ThinPrep cytology was 3.2% for biopsy-confirmed CIN 3 and 9.3% for CIN 2. Twenty-seven (87%) of the 31 women with biopsy-confirmed CIN 3 and 12 (100%) of 12 with biopsy-confirmed SCC had a diagnosis of either HSIL or greater abnormalities on ThinPrep cytology. In addition, the HPV DNA detection rates offered a good correlation between cytology and biopsy. CONCLUSION: The ThinPrep Pap performed extremely well in this primary screening trial. We found a good correlation between ThinPrep cytology and colposcopic biopsy on detection of HSIL and SCC; cervical specimens collected in ThinPrep liquid buffer serve as a direct test for HPV as well.     

Cervical smears in assessment of the natural history of human papillomavirus infections in prospectively followed women

The value of cervical (Papanicolaou) smears in monitoring the natural history of cervical human papillomavirus (HPV) infections was assessed in a series of 513 women prospectively followed since 1981. On each clinic visit, the patients were subjected to colposcopy accompanied by cervical smears and/or punch biopsies. The latter were analyzed by light microscopy for concomitant cervical intraepithelial neoplasia (CIN) and by transmission electron microscopy (TEM) for HPV particles as well as for HPV structural proteins. The stromal immunocompetent cell (ICC) infiltrates were phenotypically characterized using monoclonal antibodies for T-cell subsets, NK and K cells and Langerhans cells. HPV DNA typing was accomplished by Southern blot, spot and in situ hybridization using probes for HPV 6, 11, 16, 18 and 31. Lesions showing only changes consistent with HPV infection (HPV-NCIN) were associated with less severe atypia in cervical smears than were lesions with coexistent CIN (HPV-CIN). Normal smears were observed, however, in 24.7% of the cases with HPV-NCIN lesions, in 11.5% of cases with HPV-CIN I lesions but only exceptionally in cases with HPV-CIN II and III lesions (2.2% and 3.3%). The percentages of the different ICC phenotypes did not correlate with the atypia in cervical smears, but there was a shift towards the lower values of the T-helper/T-suppressor (OKT4+/OKT8+) cell ratio in parallel with increasing atypia. The possibility of latent HPV infection was suggested by the detection of viral particles, HPV antigens and HPV DNA in lesions shedding normal cells in the smears. The high-risk HPV types 16 and 18 were associated with the highest frequency of severely atypical cells; in the majority of cases, the low-risk types HPV 6 and 11 presented with less severe atypia. The first cervical smear seems to be of value as a predictor of the natural history of HPV lesions, as indicated by the fact that regression was inversely and progression directly related to initial cellular atypia. The present results confirm the intimate association between HPV infections and CIN. Although the biologic potential of the HPV infections seems to be dependent on multiple factors, routine cervical smears, because of their potential value in monitoring the natural history of this infection, should constitute an important means in the prospective follow-up of these patients.     

HLA-I表达与维吾尔族妇女宫颈癌前病变及HPV16感染的关系研究

目的：观察人白细胞相关抗原I（human leukocyte antigen class I,HLA-I）表达与维吾尔族妇女宫颈癌前病变进程及高危型HPV16的关系。方法：收集维吾尔族妇女宫颈炎、宫颈内上皮瘤样病变（cervical intraepithelial neoplasia,CIN）和宫颈鳞癌患者的石蜡包埋组织标本共148例,提取组织DNA,应用PCR的方法检测HPV阳性及HPV16型别;同时采用免疫组织化学SP法检测HLA-I蛋白表达水平。结果：（1）在维吾尔族妇女中HLA-I抗原在宫颈炎、CINI-II、CINIII、SCC组中阳性表达逐渐减少,差异有统计学意义（P〈0.001）。（2）HLA-I的阳性表达下降趋势与宫颈癌临床分期、组织分化程度和淋巴结转移密切相关。（3）HPV在宫颈炎、CINI-II、CINIII、宫颈癌中的感染率分别为13%、46%、82%、95%,差异有统计学（P〈0.001）。（4）HPV16在宫颈炎、CINI-II、CINIII、宫颈癌中的感染率分别为4%、30%、68%、85%,差异有统计学（P〈0.001）。（5）在HPV16阳性标本中,存在HLA-I表达缺失的占71%（58/82）,HPV16感染与HLA-I表达呈负相关（r=-0.625,P〈0.001）。结论：（1）HLA-I表达缺陷可能是宫颈病变进展的重要标志,对宫颈癌的预测预警提供依据。（2）HPV16感染在宫颈病变的发展过程中起到了极大的促进作用,是一个很强的致癌因素。（3）HPV16感染与HLA-I表达之间的关系对揭示宫颈癌发病机制提供了客观依据。     

Distribution of High-Risk Human Papillomavirus Genotypes among HIV-Negative Women with and without Cervical Intraepithelial Neoplasia in South Africa

Objective

Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).

Methods

We report data on 8,050 HIV-negative women, aged 17–65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status.

Results

Overall, 20.7% (95% CI, 19.9–21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17–29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40–65 years).

Conclusion

HPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.     

Cervical dyskeratotic cells as predictors of condylomatous changes on biopsy

Human papillomavirus (HPV) infections cause the koilocytotic and dyskeratotic cell changes seen in cervical smears. Although the koilocyte is pathognomonic, the role of the isolated dyskeratocyte in predicting the presence of HPV infection is not yet defined. One hundred patients, ranging in age from 7 to 71 years (mean: 26 years), with a cytologic diagnosis of dyskeratotic cells and a simultaneous, colposcopically directed cervical biopsy, were studied to determine the tissue correlates of such cells. On biopsy, 61 had condylomatous changes; 14 of the 61 had an associated cervical intraepithelial neoplasia (CIN). Of the 39% without condylomatous changes, 12 had an unremarkable biopsy, 19 had squamous metaplasia, 5 had hyperkeratosis and 3 had CIN. Condyloma plus CIN was diagnosed at least two months previously in 14 of these 39 patients; 6 had CIN alone. The results show that dyskeratocytes in cervical smears are predictive of a simultaneous HPV infection in 61% of the cases and of an infection at some time in 75% of the cases. Since only 14% of the patients had a condyloma plus CIN and 3% had CIN alone, patients with a smear diagnosis of dyskeratotic cells may need a more careful follow-up. Other histologic correlates of the dyskeratocyte included squamous metaplasia and hyperkeratosis.     

Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga,South Africa

P. J. Swanepoel, P. Michelow, R. Du Plessis, I. G. Proudfoot, G. A. Tarr, S. L. Bockel, C. J. Swanepoel
Cervical squamous intraepithelial lesions and associated cervical infections in an HIV‐positive population in Rural Mpumalanga, South Africa Background: The incidences of genital human papillomavirus (HPV) infection, associated squamous intraepithelial lesions and cervical squamous cell carcinoma are significantly increased in HIV‐positive women. The role of other cervicovaginal infections in the acquisition of the HPV infection, cervical carcinogenesis and genital HIV infection remains largely speculative. Methods: A retrospective study was conducted including 1087 HIV‐positive women in rural Mpumalanga province, South Africa, for the period 1 May 2009 to 31 August 2010. For each patient, the age at first presentation, cervical cytological diagnosis, subsequent follow‐up cytology and histology, and microscopically visible infections (including endemic Bilharzia) were tabulated and statistically analysed. Results: The prevalence of low‐grade squamous intraepithelial lesion (LSIL), high‐grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, atypical squamous cells of undetermined significance (ASC‐US) and atypical squamous cells, cannot exclude HSIL (ASC‐H) in the study population were 22.1%, 30.9%, 0.6%, 13.5% and 4.0%, respectively. LSIL, HSIL and squamous cell carcinoma were diagnosed, respectively, at the average ages of 35.7, 37.9 and 37.2 years. Four patients with cervical intraepithelial neoplasia grade 1 (CIN1), 32 with CIN2/CIN3 and two with cervical squamous cell carcinoma were also diagnosed with Bilharzia. Of the other infections only bacterial vaginosis had a positive statistical correlation with HPV‐induced cervical abnormalities (LSIL, HSIL or squamous cell carcinoma). Conclusion: This study confirms the high prevalence of progressive HPV‐associated cervical disease in a rural Southern African HIV‐positive population, which is at least equal to or worse than in other African HIV‐positive studies. The high incidence of Bilharzia infection in those cases that underwent cervical cone excision suggests a possible relationship with progressive HPV disease and cervical carcinogenesis. Bacterial vaginosis (perhaps in combination with Bilharzia) may compromise the normal barriers against HPV and HIV infection.     

Correlation of immunochemical detection of HPV L1 capsid protein in pap smears with regression of high-risk HPV positive mild/moderate dysplasia

OBJECTIVE: To immunostain Pap smears of high-risk (hr) HPV DNA-positive early squamous lesions for detecting HPV L1 protein. STUDY DESIGN: Routinely stained archival slides from 84 mild and moderate hrHPV DNA-positive dysplasias were immunostained using a panreactive HPV L1 antibody. Follow-up smears were taken from women with remission for a mean period of 22.8 months (range, 6-46). Conization was done in patients with persistence or progression (3 and 48 patients, respectively) after a mean time of 12 months (range, 9-48). RESULTS: Twenty-nine of 84 smears (34.5%) had positively stained squamous epithelial cell nuclei. In 9 of 29 (31%) women progressive disease occurred (2 cervical intraepithelial neoplasia [CIN] 2 and 7 CIN 3 lesions on conization) 20 (69%) had remission. Of the 55 L1-negative cases, 13 (23.6%) had remission, 42 (76.4%) progressed (3 CIN 2, 38 CIN 3, 1 microinvasive carcinoma). The difference in follow-up between L1 positive and negative cases was statistically significant (chi2 test, p< or =0.001). CONCLUSION: Low and moderate dysplastic squamous lesions without immunochemically detectable HPV L1 protein are significantly more likely to progress than are L1-positive cases. Immunochemical L1 capsid detection in routine Pap smears thus offers prognostic information about early dysplastic lesions.     

Prevalence of human papillomavirus among Croatian women attending regular gynecological visit

Human papillomavirus (HPV) infection has been identified as major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. About 40 HPV viral types are commonly found in the genital tract. Most HPV infections resolve spontaneously, while persistent infection with oncogenic types, namely HPV 16 and 18 is necessary for CIN to occur and progress to cancer. Cervical screening is presently based on the Pap smear that is designed to diagnose precancerous lesions and cervical cancer The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among 361 women attending regular gynecological visit. There were 205 women (29+/-8 years old) without determined abnormal cervical lesions and 156 women (34+/-15 years old) with abnormal Pap smear; low grade squamous intraepitehelial lesions (LSIL, n=69), high grade squamous intraepithelial lesions (HSIL, n=72) and atypical squamous cells of undetermined significance (ASCUS, n=15). HPV DNA detection and genotyping was performed by Hybrid Capture 2 assay and additionally by consensus and type-specific primers directed PCR. The overall prevalence of high-risk HPV (hrHPV) in women with abnormal Pap smears was 67.9% (106/156), of which in ASCUS 33.4% (5/15), LSIL 62.3% (43/69) and HSIL 80.6% (58/72). In HPV positive specimens, HPV 16 was found as predominant type in 60.4% cases, followed by HPV 31 (8.5%), HPV 33 (6.6%) and HPV 18 (3.7%). In the group of women without obvious cervical changes the overall hrHPV prevalence was 35.6% with HPV 16 found in 43.8% cases, followed by HPV 31 (17.8%), HPV33 (9.5%) and HPV18 (6.8%). In both study groups, women with and without cervical lesions, the prevalence of HPVof indeterminate type was 14.2% and 13.7%, respectively. Our results indicate that cervical intraepithelial lesions are largely associated with HPV type 16, followed by HPV types 31, 33, 18 and HPV of indeterminate type. Although there is a significant difference in hrHPV DNA prevalence among two groups, no significant differences between particular hrHPV types distribution were observed.     

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia,Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goi s (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.     

Human papillomavirus and cervical intraepithelial neoplasia in women who subsequently had invasive cancer.

In a retrospective case-control study biopsy specimens of cervical intraepithelial neoplasia (CIN) lesions from 47 women in whom invasive cancer subsequently developed (cases) and from 94 control subjects in whom CIN was diagnosed within 6 months of the diagnosis for the matched case subject but invasive disease did not develop were tested for human papillomavirus (HPV) DNA with tissue in-situ hybridization. There were no significant differences in the frequency of detection of HPV DNA between the two groups. In a cross-sectional survey the prevalence of HPV DNA was found to be 11% in specimens without CIN, 27% in those with CIN I, 49% in those with CIN II and 56% in those with CIN III. The positivity rates for HPV 16/33 DNA increased with the severity of CIN, but this was not observed for HPV 6/11 and 18 DNA. A comparison of the results of the case-control and cross-sectional studies suggested that the younger cohort of women had higher prevalence rates of HPV DNA than the older cohort.     

Improved rate of high-grade cervical intraepithelial neoplasia detection in human papillomavirus DNA hybrid capture testing

BACKGROUND: Numerous studies have established a link between human papillomavirus (HPV), squamous intraepithelial lesions (SIL) and carcinoma of the cervix. Testing for HPV DNA in addition to cytology in screening programs for cervical cancer has been suggested to increase detection rates. STUDY DESIGN: HPV DNA testing (performed by hybridization antibody capture assay I or II), cytology and biopsy (performed within 1 month of each other) were retrospectively reviewed for a series of 155 women. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HPV testing vs. cytology were calculated using biopsy as the gold standard. These values were also calculated in a subgroup of 37 individuals older than 35 years. RESULTS: The sensitivity, specificity, PPV and NPV of DNA hybrid capture HPV testing for detecting high-grade cervical intraepithelial neoplasia (CIN) were 86%, 44%, 26% and 93%, respectively. The respective values for cytology detection of high-grade CIN were 17%, 97%, 56% and 82%. CONCLUSION: HPV testing was significantly more sensitive for detecting high-grade CIN than cytology (86% vs. 17%). Our data support immediate colposcopy and biopsy, rather than follow-up Papanicolaou testing, if the test for HPV DNA is positive for an intermediate- to high-risk type.     

Significance of high-risk human papillomavirus DNA-positive atypical squamous cells of undetermined significance pap smears in perimenopausal and postmenopausal women

OBJECTIVE: To determine the risk of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2 or 3 in perimenopausal and postmenopausal women with high-risk human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS) on Pap tests. STUDY DESIGN: A total of 752 perimenopausal and postmenopausal women (patients 45 years) with an ASCUS interpretation on ThinPrep Pap tests were identified in 2002 and 2003. High risk HPVDNA was detected in 191 (25.4%) women. The follow-up results in these 136 women were compared with those of women <45 years. RESULTS: Of the 136 perimenopausal and postmenopausal women, 64.7% became negative on cytology or biopsy and 30.9% revealed persistent low-grade SIL (LSIL)/CIN 1. Furthermore, 5 women (3.68%) were diagnosed with HSIL/CIN 2 or 3, and 1 patient had squamous cell carcinoma (0.74%). The rate of HSIL/CIN 2 or 3 or worse detected in perimenopausal and postmenopausal women was significant lower than 10.6% in women <45 years (p = 0.028). CONCLUSION: Our study showed that perimenopausal and postmenopausal women with high-risk HPV positivity and an ASCUS interpretation have a significantly lower risk of HSIL/CIN 2 or 3 detected. Nonetheless, the risk of a significant finding on workup, including invasive carcinoma, indicates the need for colposcopic evaluation of these women.     

Prevalence of human papillomavirus genotypes in cervical cancer and precursor lesions

There are no data obtained in biopsy material on the prevalence of human papillomavirus (HPV) and HPV genotypes in Croatian women with cervical carcinoma and precursor lesions. Therefore, the prevalence of HPVand HPVgenotypes was investigated in archival material of cervical carcinoma and precursor lesions kept at Department of Pathology, School of Medicine, University of Rijeka. DNA was isolated from formalin fixed, paraffin embedded tissue, histologically classified as cervical intraepithelial neoplasia (CIN) III (n =43), squamous cell carcinoma (SCC) (n =54) and adenocarcinoma (ADC) (n =40). HPV testing was performed bypolimerase chain reaction (PCR) using generic and genotype specific primers. The prevalence of HPV DNA was 93.02%, 92.59%, and 92.5% in CIN III, SCC and ADC, respectively. In CIN III and SCC, HPV-16 was the most common high-risk genotype, identified in 65% and 52%, followed by HPV-18 in 22.5% and 28% of cases, respectively. HPV-18 showed a statistically significant prevalence in ADC (67.6%) as compared with SCC (chi(2)=9.924; p_ 0.01). Study results revealed a high prevalence of HPV-DNA in examined cervical lesions (>90%). HPV-16 predominated in SCC and HPV-18 in ADC. Single infection was more frequently present than multiple infections in all three histological groups.     

A human papillomavirus testing system in women with abnormal Pap results: a comparison study with follow-up biopsies

OBJECTIVE: To evaluate the efficacy of INFORM HPV using the SurePath collection method in women whose Pap tests indicated abnormal results. STUDY DESIGN: Ninety-two women from the gynecology clinics at The University of Texas M.D. Anderson Cancer Center who had Pap tests and underwent follow-up biopsies were selected for the study. This included 51 women with atypical squamous cells of undetermined significance (ASCUS), 23 women with low-grade squamous intraepithelial lesion (LSIL), 15 women with high-grade squamous intraepithelial lesion (HSIL) and 3 women with negative Pap results. The INFORM HPV, an in situ hybridization assay, testing for oncogenic types of HPV was performed, and the results were compared with follow-up biopsies. RESULTS: The positive rate of the INFORM HPV increased with higher grades of cytology diagnoses. The sensitivity of the INFORM HPV testing for predicting high-grade cervical intraepithelial neoplasia (CIN 2/3) also increased with higher grades of cytology diagnoses. A negative predictive value (NPV) of 94.9% and a specificity of 80.4% for predicting CIN 2/3 were observed in the ASCUS group. CONCLUSION: Using SurePath Pap specimens, the INFORM HPV lacks sufficient sensitivity and NPV for predicting CIN 2/3 in women with ASCUS. Therefore, use of the test as a triage tool is limited.     

TCT、HPV检测在宫颈锥切术后复发中的预测价值

目的:评估薄层液基细胞学检查(thinprep cytologic test,TCT)和人乳头瘤病毒(human papillomavirus,HPV)检测在宫颈锥切术后复发中的预测价值。方法:随访531例病理诊断为子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)Ⅱ-Ⅲ级接受宫颈锥切术的患者,分别于术后3、6个月及术后每6-12月随访1次,以TCT及HPV检测作为随访的检测指标,若二者有一项异常,行阴道镜下活组织检查,病理证实存在子颈上皮内瘤变Ⅰ-Ⅲ级者视为复发。采用敏感度、特异度、阳性预测值、阴性预测值表示TCT、HPV检测性能。结果:531例患者中10%(54例)的患者出现不同级别的病变复发。TCT在术后预测病变复发的灵敏度77%,特异度72%;HPV在术后预测病变复发的灵敏度95%,特异度60%,TCT联合HPV预测病变复发的灵敏度100%,特异性80%。术后HPV负荷量100 RLU/PC者较HPV负荷量100 RLU/PC者而言术后病变复发的风险增高,差别有统计学意义(P0.01),术后HPV负荷量100 RLU/PC是锥切术后病变复发的高危因素。结论:使用细胞学联合HPV检测是有效的预测宫颈锥切术后病变复发的方法,术后高HPV负荷量与病变复发相关,并可对术后复发高风险人群进行分流,临床需严密随访。     

Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

Objective

Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology.

Methods

Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.

Results

Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03).

Conclusion

The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future CIN3, indicating that HPV-mRNA-negative women are at low risk of progression to high grade CIN.     

Genital human papillomavirus testing by in situ hybridization in liquid atypical cytologic materials and follow-up biopsies

OBJECTIVE: To describe cases of HPV testing by DNA in situ hybridization performed on atypical cervicovaginal samples collected by a liquidsed method that were negative for HPV DNA on cytology but revealed cervical intraepithelial neoplasia on follow-up biopsies. STUDY DESIGN: Three hundred ninety-five consecutive SurePath atypical squamous cells of undetermined significance (ASC-US) cytologic samples from asymptomatic, reproductive-age women were tested for human papillomaviruses (HPVs) by the in situ hybridization (ISH) method (Ventana Inform HPV Test, Tucson, Arizona, U.S.A). One hundred (25%) cases underwent follow-up colposcopic biopsy within 3 months of cytology. All the tests (cytology, ISH, histology) were independently evaluated without knowledge of the other tests. RESULTS: One hundred twenty-two (33%) cytologic samples were positive for HPVs. Of a total of 100 (HPV positive and negative) follow-up biopsies, 55 were positive for cervical intraepithelial neoplasia (CIN). Fourteen cases of biopsy-proven CIN tested negative for all HPV types in the prior cytologic samples. Retesting of the 14 CIN tissues by ISH was negative in 10, positive for HPV in 2 and inconclusive in 2. CONCLUSION: There is a small but significant (14%) false negative rate with HPV testing by the Ventana ISH method. Clinically suspicious cases should be followed even if an HPV test is negative.