宫颈癌及上皮内瘤变人乳头瘤病毒基因型的检测

目的:了解宫颈癌及上皮内瘤变人乳头瘤病毒(HPV)的感染率及其基因型的分布。方法:用PCR-RFLP法检测239例宫颈癌及上皮内瘤变患者HPV感染并进行分型。先用PGMY09/11共同引物扩增生殖道粘膜型HPV L1区的高度保守区,然后联合使用RsaⅠ、MseⅠ、PstⅠ和HaeⅢ4个限制性内切酶对阳性PCR产物进行酶切,利用不同的酶切片段鉴定HPV的基因型。结果:在239例宫颈癌及上皮内瘤变患者中共检出205例(85·8%)HPV感染,其中宫颈上皮内瘤变Ⅰ级(CINⅠ)、宫颈上皮内瘤变Ⅱ~Ⅲ级(CINⅡ~Ⅲ)和宫颈癌中HPV感染率分别是66·7%,89·9%和98·3%,差异有统计学意义(P<0·001)。在宫颈癌及上皮内瘤变中共检出22型HPV,其中主要基因型及其感染率分别是HPV16(45·6%)、58(12·1%)和52(6·3%)。结论:宫颈癌及上皮内瘤变中HPV感染的基因型至少可达22型,其中以HPV16、58和52为最常见。     

Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation

OBJECTIVE: To estimate the effectiveness of Hybrid Capture II to predict high-grade cervical intraepithelial neoplasia (CIN) from a cytological cervical sample. Evidence of high-risk human papillomavirus (HPV) was also determined from biopsy samples using the polymerase chain reaction (PCR) for women referred with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou smears. METHODS: We screened 8170 women with Papanicolaou smears, of whom 278 (3.4%) returned ASCUS. All ASCUS cases underwent colposcopy and Hybrid Capture II testing. High-grade CIN biopsy specimens were tested for high-risk HPV by PCR. RESULTS: Nearly 30% of ASCUS cases had CIN biopsy results (11.9% showing CIN II or CIN III and 17.6% showing CIN I). Hybrid Capture II positive rates were 93.3% for cases with CIN III, 72.2% for CIN II, and 51.0% for CIN I (P <.001). ASCUS-Premalignant Process Favored cases showed a 28.1% high-grade biopsy rate and a 100% Hybrid Capture II positive rate. For ASCUS-Undefined and ASCUS-Reactive Process Favored cases, Hybrid Capture II returned positive in 90.9% of CIN III and 61.5% of CIN II cases (P <.001). Sixty-nine of 178 (38.8%) patients with no evidence of CIN tested positive for Hybrid Capture II. Human papillomavirus deoxyribonucleic acid (DNA) high-risk subtypes were detected by PCR in the tissue of all high-grade CIN cases with negative Hybrid Capture II results. CONCLUSION: Hybrid Capture II returned negative in 25% of cases with biopsy-proven high-grade CIN with associated high-risk HPV DNA by PCR (non-Premalignant ASCUS subset), and positive in 39.3% of cases with normal results; this limits its clinical utility.     

Human papillomavirus genotyping using HPV DNA chip analysis in Korean women

This study was designed to investigate the genotypes of human papillomavirus (HPV) in Korean women who had abnormal cervical cytology and to evaluate the clinical accuracy of HPV DNA chip analysis for the diagnosis of cervical neoplasia. Liquid-based cytology preparations, HPV DNA chip analysis, and cervical biopsy were performed in 2358 women. High-risk HPV was identified in 23.5% of 1650 histologically confirmed normal samples (including cervicitis and squamous metaplasia) and in 81.8% of 708 samples with cervical intraepithelial neoplasia (CIN) and carcinoma (P<0.01). The major prevalent high-risk HPV genotypes in 381 samples of CIN II/III were HPV-16, -58, -33, and -31, in order of prevalence rate (average overall, 78.0%), and HPV-16, -18, -58, and -33 (average overall, 81.2%) in 133 samples of squamous cell carcinoma (SCC). The infection rate of HPV-16 was significantly higher than that of other high-risk HPV genotypes in all normal, CIN, and SCC cases (P < 0.01) and increased with more advanced squamous cervical lesions (P<0.01). The detection accuracy of high-risk HPV using HPV DNA chip analysis for CIN II or worse was as follows: sensitivity 84% (81-87%), specificity 72% (70-74%), positive predictive value 47% (44-50%), and negative predictive value 94% (92-95%). These results suggest that HPV DNA chip analysis may be a reliable diagnostic tool for the detection of cervical neoplasia and that there are geographic differences in the distribution of high-risk HPV genotypes.     

Role of human papillomavirus (HPV) testing in the follow-up of patients after treatment for cervical precancerous lesions

OBJECTIVE: To evaluate the role of human papillomavirus (HPV) testing in post-treatment follow-up of patients after therapeutic excision of the cervix due to positive screening tests. STUDY DESIGN: A hospital-based retrospective analysis was performed with prospective collection of patient data of women screened for cervical cancer at a Gynecologic Outpatient Clinic. Patients after therapeutic excision due to positive screening results were identified and followed up with HPV testing and serial cytology. RESULTS: After 61 treatment for cervicalis intraepithelialis neoplasia (CIN), high-risk HPV infection was detected during the post-treatment follow-up at 18 cases (29.5%), 10 of them had persisting cytological atypia (positive predictive value (PPV): 56%), 5 developed CIN (PPV: 28%). When the HPV test was negative (43 patients) in the post-treatment period, neither CIN nor persisting cytological atypia developed (negative predictive value (NPV): 100%) during 1201 patient months (median 26 months). CONCLUSIONS: A negative HPV test eliminates the risk of recurrent disease after treatment for CIN.     

高危型人乳头状瘤病毒DNA检测与细胞学联合检查对子宫颈癌前病变筛查的研究

目的评价高危型人乳头状瘤病毒(HPV)DNA检测联合宫颈细胞学检查对宫颈癌前病变筛查的效果。方法2003年1月至2004年6月,对广东省人民医院妇科门诊5210名妇女进行宫颈癌前病变筛查,采用第二代杂交捕获试验(HC-Ⅱ)检测高危型HPV DNA联合细胞学检查,同时进行阴道镜检查,并以宫颈活检的组织病理学结果为确诊标准。结果受检者平均年龄(34±9)岁,筛查并最后经病理诊断为HPV感染890例,宫颈上皮内瘤变(CIN)Ⅰ级83例,CINⅡ73例,CINⅢ80例,宫颈浸润癌54例,子宫内膜癌5例,阴道上皮内瘤样病变1例,宫颈结核1例。以组织病理学为确诊标准,高危型HPV DNA检测CINⅡ、Ⅲ的敏感度是92·22%,特异度是74·71%,阳性预测值5·19%,阴性预测值99·84%。宫颈细胞学筛查CINⅡ、Ⅲ,以未明确诊断意义的不典型鳞状上皮细胞(ASCUS)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是90·00%、80·34%、11·94%和99·63%;以低度鳞状上皮内病变(LSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是70·13%、91·58%、11·11%和99·51%;以高度鳞状上皮内病变(HSIL)为分界点的敏感度、特异度、阳性预测值和阴性预测值分别是48·05%、98·46%、31·90%和99·21%。高危型HPV DNA检测联合细胞学检查筛查CINⅡ、Ⅲ的敏感度、特异度、阳性预测值和阴性预测值分别是98·70%、73·08%、5·21%和100·00%。高危型HPV DNA在不同宫颈病变中的阳性率分别是:宫颈癌85·2%(46/54),CINⅢ92·5%(74/80),CINⅡ86·3%(63/73)和CINⅠ45·8%(38/83)。结论高危型HPV DNA检测在宫颈癌前病变的筛查中有很高的敏感度和阴性预测值,高危型HPV DNA检测联合细胞学检查可使敏感度和阴性预测值有提高,但特异度未能提高。     

Evaluation of the Possible Protective Role of Adeno-Associated Virus Type 2 Infection in HPV-Associated Premalignant Disease of the Cervix

Objective. Our objective was to examine the prevalence of adeno-associated virus (AAV) infection in women with normal cervical smears and those with HPV-associated cervical intraepithelial neoplasia (CIN).Methods. HPV typing was performed on DNA from cervical smears of 211 women with CIN (CIN 1 = 83, CIN 3 = 128) and 433 healthy women who had a normal cervical smear. HPV typing was performed on all cases and controls using type-specific oligonucleotide primers (HPV 16, 18, 31, 33). AAV DNA was amplified by nested PCR from the same samples. The amplified DNA were separated on 2% agarose gels, blotted, and hybridized to AAV-2 DNA labeled by random priming with [α-³²P]dCTP to confirm specificity of amplification.Results. A total of 131 cases of CIN were positive for one of the HPV types either alone or in combination. HPV 16 was present in 120 (57%) cases, HPV 18 in 15 (7%), HPV 31 in 27 (13%), and HPV 33 in 15 (7%) and there were multiple HPV types detected in 34 (16%) cases. All of the controls were selected to be negative for HPV. A total of 6/433 (1.4%) control cervical smears and 4/211 (1.9%) of CIN (CIN1 = 2; CIN3 = 2) contained AAV DNA. No correlation between AAV and any clinical feature was observed.Conclusions. These results are different from some that have been previously published and suggest that AAV DNA is not frequently present in either normal control cervical samples or cervical intraepithelial neoplasia. This does not support the hypothesis that AAV may be protective against cervical cancer. Further research is necessary to understand the natural history of AAV infection and its role in human disease.     

Role of human papillomavirus testing in reducing the number of surgical treatments for precancerous cervical lesions

PURPOSE OF INVESTIGATION: To determine whether the addition of the Hybrid Capture II (HC II) test (Digene Corp., Gaithersburg, MD, USA) to cytological, colposcopical and histological results could reduce the number of surgical treatment procedures for precancerous cervical lesions. METHODS: Surgical treatment of precancerous cervical lesions was performed in 181 women. Priorly, the women were tested for high-risk human papillomavirus (HPV). Sensitivity, specificity, positive and negative predictive value were calculated to assess the performance characteristics of HC II in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and grade 3 or worse (CIN 3+). RESULTS: Eighty (44.2%) women had a histological result < CIN 2; 117 (64.6%) women had < CIN 3. Fifty-three (29.3%) women with < CIN 2 tested HPV negative; 69 (38.1%) women with < CIN 3 tested HPV negative (p < 0.05). The sensitivity of HC II for detecting CIN 2+ and CIN 3+ was 76.2% and 87.5%, respectively. CONCLUSION: A high proportion of women were overtreated probably due to cytological and histological overestimations. HPV testing would reduce the number of unnecessary surgical treatments and should be used as an additional screening tool.     

Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2-3)

ObjectiveTo identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2–3).MethodsProspective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearson's chi-square test was used for statistical analysis.ResultsHPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant (p = 0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types.ConclusionOnly 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.     

黑龙江省铁力市育龄妇女宫颈癌前病变筛查的研究

目的:检测目标人群中宫颈病变的现状及人乳头瘤病毒(human papillomavirus,HPV)流行病学特征。方法:(1)应用醋酸白试验(VIA)、碘不着色试验(VILI)对4007例妇女宫颈行肉眼观察,疑似异常病例行阴道镜检查,异常病例组织活检确诊;(2)采用导流杂交基因分型技术(HybriMax),对宫颈癌及CIN(cervical intraepithelial neopla-sia)患者进行21种HPV基因型的分型检测,分析HPV感染率以及宫颈疾病发病状况。结果:(1)两年诊断出宫颈病变发病率为5.01%,其中CINⅠ3.74%,CINⅡ0.87%,CINⅢ/原位癌0.32%,浸润癌0.07%;(2)病变宫颈HPV-DNA基因分型检测到HPV-DNA阳性127例,阳性率63.18%,其中CINⅠ53.33%,CINⅡ91.43%,CINⅢ92.30%,宫颈浸润癌100%;高危型HPV感染136例次,占77.27%,低危型40例次,占22.73%;单一亚型感染89例,占70.08%,多重HPV基因型混合感染38例,占29.92%。感染最多的基因型是HPV16,共45例次,占25.57%,其次是HPV58,占10.23%,随后基因型由高到低依次为:HPV52,占10.23%;HPV33,占7.95%;HPV6,占6.82%,不同级别CIN及浸润癌HPV感染率差异有统计学意义(P0.05)。结论:(1)肉眼观察筛查宫颈病变虽有一定的漏诊率,但由于检查成本低廉,在经济欠发达地区,仍可作为防癌普查的基本方法;(2)HPV16型是本地区宫颈病变HPV感染的主要型别,位居第二为HPV58,HPV52、HPV33、HPV6分别位居第三、四、五位。加大对高危人群的普查力度势在必行。     

Value of HPV-DNA test in women with cytological diagnosis of atypical glandular cells (AGC)

Objective

This study analyzed whether HPV (human papillomavirus) testing contributes towards defining histological abnormalities in women with atypical glandular cells (AGC) diagnosed at cervical cytology.

Study design

One hundred and eight women with conventional cervical cancer screening smears suggestive of AGC not otherwise specified (AGC-NOS) and favor neoplastic (AGC-FN) were consecutively enrolled. All women underwent colposcopic examinations and biopsy was performed according to the cytopathologic and/or colposcopic abnormalities present. All specimens were tested for high risk HPV genotypes by Roche's polymerase chain reaction reverse line blot assay. The chi-square test was used to evaluate the association between HPV findings and a diagnosis of high-grade pre-invasive or invasive disease (CIN 2 or worse) taking negative tests or CIN 1 as a reference. Odds ratios (OR) with their respective 95% confidence intervals (95%CI) were used to evaluate the magnitude of the association between HPV testing and CIN 2 or worse. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated.

Results

Final diagnosis revealed a negative outcome in 80 cases (74%), cervical epithelial neoplasia 1 (CIN 1) in 13 cases (12%), CIN 2 or worse in 12 cases (11%) and glandular neoplasia in 3 (3%) cases. The overall detection rate of HPV was 21% (23/108). Neoplasia was significantly associated with positive HPV-DNA in women with AGC-NOS (OR = 15.21; 95%CI: 2.64-87.50); however, there was no significant association between a histological diagnosis of neoplasia and HPV positivity in women with AGC-FN (OR = 3.00; 95%CI: 0.36-24.92). The sensitivity, specificity, positive predictive value and negative predictive value of HPV-DNA testing for the detection of CIN 2 or worse in women with AGC-NOS were 71%, 86%, 29% and 97%, respectively. In women with AGC-FN, these values were 50%, 75%, 66% and 60%, respectively.

Conclusions

HPV testing at the time of colposcopy for patients with AGC in whom no colposcopic abnormality is found may be a powerful ancillary tool for identifying women at a high risk of underlying significant cervical lesions.     

Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases

OBJECTIVE: To assess the usefulness of human papilloma virus (HPV) typing for predicting pre-malignant and malignant cervical lesions. STUDY DESIGN: 314 women, who underwent colposcopy, biopsies and high and low-risk HPV typing after a confirmed abnormal routine Pap test were studied. HPV-DNAs were typed by using PCR technique. RESULTS: We found a significant increasing rate of high-risk-HPV by the increasing severity of histology, ranging from 40% in negative cases to 86.9% in those with CIN3 lesions. The positive predictive value of high-risk-HPV ranged from 13.3% in patients with atypical squamous cells of undetermined significance (ASCUS) to 29.4% in those with HSIL. By contrast, negative predictive value was 96% in patients with ASCUS, 97.2% in low-grade squamous intraepithelial lesions (LSIL), and 71.4% in high-grade squamous intraepithelial lesions (HSIL). Sensitivity and specificity for detecting CIN2 or CIN3 was 86.0% and 41.3%, respectively. CONCLUSIONS: The high negative predictive value of high-risk HPV testing suggests that HPV negativity could be used for predicting the absence of important cervical lesions, and therefore avoiding unnecessary colposcopy in ASCUS and LSIL cases.     

Epidemiological study in Okinawa, Japan, of human papillomavirus infection of the uterine cervix

OBJECTIVE: To investigate the prevalence and type distribution of human papillomavirus (HPV) in women with normal cervical cytology and with cervical intraepithelial neoplasia I to III(CIN) or carcinoma of the cervix in Okinawa, Japan. METHODS: We investigated HPV DNA in 4,078 subjects with cytologically normal cervices, 279 subjects with CIN, and 383 subjects with cervical cancer in Okinawa Prefecture in Japan. The presence of HPV DNA was also compared among generations. HPV DNA was both detected and typed using polymerase chain reaction (PCR). RESULTS: The HPV positivity rate was 10.6% in the subjects who were normal on cervical cytodiagnosis. In each generation, the positivity rate was 20.4% in women aged 20-29 years and approximately 10% in the groups aged 30-89 years, with significant differences among generations. The HPV positivity rates in CIN and cervical cancer groups were 76.0% and 86.2%, respectively, with no significant difference between the groups. The positivity rate of HPV 16 decreased with age in both CIN and cervical cancer groups. CONCLUSION: Among non-cancer subjects, HPV infection rates were almost 20% in women aged 20-29 years and 10% in women aged 30-89 years. HPV16-positive CIN or carcinoma were more prevalent in the younger women, suggesting that HPV16-infected epithelial cells rapidly progress to cervical cancer.     

Analysis of transforming gene regions of human papillomavirus type 16 in normal cervical smears

Summary Exfoliated cells from the uterine cervix of 102 Hungarian women with no cytological abnormality were screened using the polymerase chain reaction (PCR) for human papillomavirus (HPV) type 16 infection. Twenty-nine patients with histologically confirmed cervical intraepithelial neoplasia (CIN) served as reference cases. PCR was performed with 2 different HPV 16 specific oligonucleotide primer pairs flanking a 300 and a 200 base-pair fragment from the early 6 (E6) and early 7 (E7) genes, position 215–514 and 605–805. The specimens exhibited the same proportions of type 16 sequences specific for the tested regions. 8.8% (9/102) of normal samples showed amplification for HPV type 16 E6 and E7 regions, while 48.3% (14/29) of CIN biopsies were positive for the same gene sequences.     

Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia

Multicenter international phase III clinical trials using multivalent human papillomavirus (HPV) vaccines for cervical cancer (CC) prevention are underway. As HPV immunity is type specific, defining HPV genotype prevalence in different regions to ascertain whether predominant types differ geographically is considerably important prior to vaccine implementation. This study aimed to define HPV genotypes present in CC and high-grade dysplasia among women in Melbourne, Australia. HPV genotype analysis of a cross section of women in Melbourne with cervical dysplasia/cancer was performed. A total of 493 cervical biopsies from patients being treated for moderate (n= 122) or severe (n= 180) cervical intraepithelial neoplasia (CIN II/III) or CC (n= 191) were tested for HPV genotypes using the PGMY09/11 primer system and line blot assay. HPV detection rates were 63.9%, 72.8%, and 86.9% in CIN II, CIN III, and CC biopsies, respectively. The most prevalent HPV genotypes among CC biopsies were HPV-16 (52.9%), HPV-18 (18.3%), HPV-45 (6.3%), HPV-39 (3.1%), and HPV-73 (2.6%). Multiple HPV infections, comprising two to five types, were identified in 14.4% of biopsies, being significantly fewer (5.2%) among CC biopsies (P < 0.0001). These results indicate that the two most prevalent CC-associated HPV genotypes in Australia parallel those described internationally, with type variations thereafter.     

Human papillomavirus testing in primary screening for cervical cancer of human immunodeficiency virus-infected women, 1990-1998

OBJECTIVE: Women infected with the human immunodeficiency virus (HIV) have an increased risk of cervical neoplasia while the value of cytologic screening is limited due to a high prevalence of inflammatory disease. The study was conducted to determine whether testing for human papillomavirus (HPV) DNA could improve primary screening for cervical cancer of these patients. METHODS: One hundred thirty-eight HIV-infected women were examined between 1990 and 1998. Ninety-four patients with a total of 279 women-years were eligible for incidence evaluation. Colposcopy, cytology, and HPV DNA testing with the hybrid capture I assay were performed at each visit. RESULTS: Seventeen cases of high-grade cervical neoplasia were diagnosed at study entry and 13 developed CIN II or CIN III during follow-up. The hybrid capture I assay detected 94.1% of prevalent and 100% of incident high-grade neoplasia, while the corresponding sensitivity of Pap smears using CIN I or worse as the referral criteria was 82.3% for prevalent and 69.2% for incident high-grade neoplasia. Eleven of 13 patients who progressed to histologically confirmed CIN II/III tested positive for HPV DNA at study entry compared with 5/13 women presenting with any degree of cytologic atypia at recruitment. The Pap smears of 36/94 women remained normal throughout the study while 54/94 patients remained negative for high-risk HPV types. CONCLUSION: Hybrid capture I identified high-grade cervical neoplasia more accurately than the Pap smear and appeared to be beneficial for primary cervical cancer screening in HIV-infected women.     

Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.     

Human Papillomavirus Testing in Primary Screening for Cervical Cancer of Human Immunodeficiency Virus-Infected Women, 1990–1998

Objective. Women infected with the human immunodeficiency virus (HIV) have an increased risk of cervical neoplasia while the value of cytologic screening is limited due to a high prevalence of inflammatory disease. The study was conducted to determine whether testing for human papillomavirus (HPV) DNA could improve primary screening for cervical cancer of these patients.Methods. One hundred thirty-eight HIV-infected women were examined between 1990 and 1998. Ninety-four patients with a total of 279 women-years were eligible for incidence evaluation. Colposcopy, cytology, and HPV DNA testing with the hybrid capture I assay were performed at each visit.Results. Seventeen cases of high-grade cervical neoplasia were diagnosed at study entry and 13 developed CIN II or CIN III during follow-up. The hybrid capture I assay detected 94.1% of prevalent and 100% of incident high-grade neoplasia, while the corresponding sensitivity of Pap smears using CIN I or worse as the referral criteria was 82.3% for prevalent and 69.2% for incident high-grade neoplasia. Eleven of 13 patients who progressed to histologically confirmed CIN II/III tested positive for HPV DNA at study entry compared with 5/13 women presenting with any degree of cytologic atypia at recruitment. The Pap smears of 36/94 women remained normal throughout the study while 54/94 patients remained negative for high-risk HPV types.Conclusion. Hybrid capture I identified high-grade cervical neoplasia more accurately than the Pap smear and appeared to be beneficial for primary cervical cancer screening in HIV-infected women.     

导流杂交基因芯片技术在人乳头状瘤病毒检测中应用的研究

目的评价导流杂交基因芯片技术,即凯普导流杂交HPV DNA检测法（简称HybriMax）在女性生殖道人乳头状瘤病毒（HPV）感染检测中的临床效用。初步探讨女性生殖道感染最常见的HPV基因型。方法从2004年6月—2005年5月在中日友好医院妇科行宫颈癌筛查的患者7520例中选取591例,包括宫颈细胞学检查正常者138例,异常者453例,并对异常者按组织病理学分为炎症组、宫颈上皮内瘤变（CIN）Ⅰ组、CINⅡ组、CINⅢ组、宫颈癌组和湿疣组。采用HybriMax方法对591名患者进行宫颈细胞21种HPV基因型分型检测,并对其中的413例同时采用第二代杂交捕获（HC-Ⅱ）试验行13种高危型HPV检测。另选取453例细胞学异常者中的101例患者的组织切片进行原位杂交HPV16、18检测。比较不同方法检测结果的一致性,计算用HybriMax法检测的各组患者不同HPV基因型的阳性率。结果HybriMax与HC-Ⅱ两种方法检测13种高危型HPV的总符合率92．5％（382／413）,总Kappa指数（KI）0．814,宫颈癌组符合率100．0％;与原位杂交检测结果符合率89．1％（90／101）,KI为0．776。10种最常见的HPV基因型依次（按阳性率递减）为：细胞学正常者16、68、18、52、58、11、53、31、39、33;细胞学异常者16、52、58、18、33、31、81、53、68、66,宫颈癌组16、18、52、58、33、66、68、31、51、53。结论HybriMax与HC-Ⅱ、原位杂交检测结果一致性良好,且能对更多基因型确切分型。官颈病变患者最常见的6种HPV基因型为16、18、52、58、33、31。     

Human papillomavirus infection in the female population of Antwerp, Belgium: prevalence in healthy women, women with premalignant lesions and cervical cancer

Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.     

Increased risk of cervical disease among human immunodeficiency virus-infected women with severe immunosuppression and high human papillomavirus load(1)

OBJECTIVE: To investigate human papillomavirus (HPV) genotypes, HPV DNA load, and behavioral and sociodemographic factors in a series of human immunodeficiency virus (HIV)-seropositive women, and to correlate HPV infection with cervical disease according to immune status. METHODS: Three hundred seven HIV-seropositive women were tested for the presence of HPV DNA by polymerase chain reaction (PCR) and Southern blot hybridization. Cervical disease was assessed using Papanicolaou smears, colposcopy, and biopsies when necessary. Various risk factors for cervical intraepithelial neoplasia (CIN) were tested using multiple logistic regression analysis. RESULTS: Cervical disease was diagnosed in 83 (27.0%) of 307 women and HPV infection in 162 (52.8%). High HPV load (as detectable by Southern blot hybridization) was found in 90 (55.6%) of the 162 infected women. Potentially oncogenic or related genotypes were detected in 74 (82.2%) of these 90 cases. High-load HPV infection was twice as frequent in severely immunosuppressed women (CD4 cell count less than 200/microL) as in women with higher CD4 cell counts (P =.002). High-load HPV infection was associated with a high risk of cervical disease (adjusted odds ratio [OR] 16.8; 95% confidence interval [CI] 7.0, 40.3). The risk among severely immunosuppressed women was ten times greater than that among women with CD4 cell counts of at least 200/microL. Low-load HPV infection (detected by PCR only) was a risk factor for CIN in severely immunosuppressed women only (adjusted OR 7.4; 95% CI 1.3, 43.0). CONCLUSION: Immunosuppression favors cervical high-load HPV infection with oncogenic genotypes and its clinical expression in HIV-seropositive women.