Human papillomavirus (HPV) testing in the management of women with abnormal Pap smears. Experience of a colposcopy referral clinic

BACKGROUND AND OBJECTIVES: Several detailed algorithms for the appropriate use of human papillomavirus (HPV) testing in the management of women with abnormal Pap (Papanicolaou) smears have been launched, but their direct country-to-country adoption is difficult. This necessitates their testing in individual settings, which is ongoing in our colposcopy referral clinic. METHODS: A series of 224 consecutive women attending the clinic with the usual referral indications (ASC-US or higher in Pap) were examined by the conventional diagnostic tools (PAP smear, colposcopy, punch biopsy) and subjected to HPV testing and viral typing for both low-risk (L-R) and high-risk (H-R) types by nested PCR-based techniques. Predictors of the high-grade diagnostic categories were analysed using both univariate- and multivariate modelling, and the performance characteristics (sensitivity, specificity, NPV, PPV) of all tests in detecting high-grade CIN were calculated. RESULTS: In the PAP test, ASC-US smears were most common (37.9%), followed by low-grade squamous intraepithelial lesions (LSIL) (26.3%) and high-grade SIL (HSIL) (4.9%). Colposcopy was performed for 180 women, of whom 48.3% had a normal transformation zone (TZ), 40.6% had ATZ1 (abnormal TZ grade 1), and 5.6% had ATZ2. In biopsy (n = 71), 49.3% had CIN1, 5.6% CIN2, and 16.9% CIN3. The HPV test was positive in 64 (28.8%) women, more often in those aged < 35 years (p = 0.025). High-grade colposcopy (ATZ2) was significantly associated with HSIL in the Pap test (OR 20.5; 95% CI: 4.34-96.47), and with HPV test positivity (OR 6.37; 95% CI: 1.58-25.73). The most significant predictors of CIN3 were HSIL in the PAP, HPV test positivity, and high-grade colposcopy. HSIL and HPV test (for H-R types), but not colposcopy, retained their significance as independent predictors of CIN3 also in adjusted multivariate models: OR 88.27; 95% CI 4.17-1867.04, and OR 19.46; 95% CI 2.01-187.75, for the HSIL and H-R HPV test, respectively. Changing the cut-off level of the Pap test from ASC-US to HSIL increased the specificity of the test up to 96.4%, with the loss in sensitivity from 87.5% to 43.8%. Colposcopy (ATZ2) had 92% specificity, and NPV competing with that of the Pap test. The sensitivity of HPV test exceeds that of the Pap test at HSIL cut-off level, but the specificity of the PAP test is clearly superior. CONCLUSIONS: Accurate predictors of significant cervical pathology (CIN3) are well defined, but the problem is the different performance of the diagnostic tools in clinical practice. A proficient combination of the tests is likely to result in the most satisfactory clinical practice in the management of women with abnormal Pap tests (MAPS).     

Colposcopy: the value of HPV testing in clinical practice

The indications for colposcopy have changed recently because of the new Bethesda terminology, the introduction of HPV testing in clinical practice, and the latest consensus guidelines on management of patients with an abnormal cervical cytological test. Colposcopy remains the reference technique to assess patients with abnormal cytological test results, especially those with ASC-H, LSIL, HSIL, and AGC. In women with an ASC-US result, colposcopic examination of only those who test positive for high-risk HPV increases the specificity of the technique. When liquid-based cytology is used, HPV DNA testing is the preferred approach in these women. In primary screening using combined cytology and HPV DNA testing in women over the age of 30, colposcopy is indicated in patients with normal cytology and two HR HPV DNA positive tests performed at a nine month interval. For the follow up of untreated patients with ASC-US/LSIL and CIN I, colposcopy carried out at one year after a single HR HPV DNA positive test is as sensitive as colposcopy after two or three abnormal cytology tests. After excision or conization in patients with high-grade CIN, colposcopy after a single HR HPV DNA positive test is as sensitive as cytology testing and colposcopy at six months. Therapeutic decisions must not be based solely on the results of HPV DNA testing except in specific cases.     

Assessment of risk factors and human papillomavirus (HPV) related pathogenetic mechanisms of CIN in HIV-positive and HIV-negative women. Study design and baseline data of the HPV-PathogenISS study

OBJECTIVES: In women with HIV-associated immunosuppression, HPV infections have an increased risk of progression to high-grade cervical intraepithelial neoplasia (CIN). With the HAART-induced prolonged survival and more protracted clinical course of AIDS, progression of CIN to cervical cancer (CC) has become a clinically relevant issue, and the mechanisms responsible for HIV-HPV interactions need further elucidation. The study design and analysis of the baseline data of our new project are presented. MATERIAL AND METHODS: This project is a combination of a prospective cohort study of HIV- and HIV+ women, and a retrospective analysis of CIN lesions and cervical cancer. Up to the present, 244 women have been enrolled (17 HIV+) and subjected to epidemiological interview, colposcopic examination, sampling for HPV testing and typing (PCR, InnoLiPA), and HPV serology. The retrospective series of biopsies were analysed for 13 biomarkers (monitoring key molecular events) using immunohistochemistry and tested for HPV by PCR and TaqMan. RESULTS: HIV- and HIV+ women differ in their exposure status to many of the key epidemiological risk factors of cervical cancer, the most significant ones being number of sexual partners (p = 0.0001), age at onset of sexual activity (p = 0.002), and contraception (yes-no) (p = 0.009). The differences in the baseline clinical observations are less dramatic; HIV-positive women had more frequent HSIL PAP tests (p = 0.040), CIN2 or higher in cervical biopsy (p = 0.049), and external genital warts (p = 0.019). The factors predicting intermediate endpoint markers of cervical cancer, i.e., HSIL PAP smear, ATZ2 in colposcopy, and high-grade CIN in biopsy were analysed in univariate and multivariate regression models. All factors significant in univariate analysis were entered in the multivariate model; HIV-status and Pap smear history maintained their independent predictive power of the HSIL Pap test. The most powerful predictor of ATZ2 colposcopy was HSIL in Pap test. Only the HSIL Pap test and ATZ2 colposcopy remained significant independent predictors of high-grade CIN (p = 0.0001 and p = 0.008, respectively) in the multivariate model. CONCLUSIONS: The three intermediate endpoint markers are closely interrelated, but predicted in part by different covariantes in the causal pathway to cervical cancer. To elucidate whether the increased risk of HIV-positive women to high-grade CIN is due a) to their different exposure status to the risk factors, b) to the direct effects of HIV, or c) to molecular interactions between HIV and HPV, we need to complete these analyses separately in HIV+ and HIV- women.     

Human papilloma virus is detectable by the Hybrid Capture 2 test in cervical smear samples from women over 40 years of age with high-grade squamous intraepithelial lesions

To establish that in Canterbury, New Zealand, women over the age of 40 with biopsy confirmed high grade squamous intraepithelial lesions (HSIL) have human papilloma virus (HPV) detectable by the Hybrid Capture 2 (HC2) test. Fifty-two women with abnormal cytology under going colposcopy had HC2 performed. HPV status, cytology and histology were compared. HC2 was positive in 30/31 with grade 2 cervical intraepithelial neoplasia (CIN2) or worse, 5/6 with HPV changes or CIN1, and 10/15 with no demonstrated abnormality.     

Expanded cytological referral criteria for colposcopy in cervical screening: comparison with human papillomavirus testing

OBJECTIVE: The goal of this study was to investigate whether expanded cytologic referral criteria for colposcopy or the addition of human papillomavirus (HPV) testing on cervical screening could improve the rates of detection of cervical intraepithelial neoplasia (CIN). METHODS: HPV testing by semiquantitative polymerase chain reaction/ELISA was performed in 1000 women who were self-referred for routine Pap smear. They underwent colposcopy following an abnormal smear result or a positive HPV test. As abnormal smear results were considered reports of low- or high-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance, and even HPV-associated reactive cellular changes (mild koilocytosis, mild dyskeratocytosis, hyperchromatic nuclei, bimultinucleation, and cleared cytoplasm). Loop excision of the transformation zone was performed in women with cytology and colposcopy indicative of CIN, as well as in women with normal cytology but positive HPV test and colposcopic impression of CIN. RESULTS: The Pap test was abnormal in 89% of the cases of CIN 1 (34/38) and 96% of CIN 2/3 (27/28) diagnosed in our population. HPV testing picked up four additional cases of CIN 1 (11%) and one case of CIN 2/3 (4%). Overall the HPV test detected 95% of the cases of CIN 1 (36/38) and 89% of the cases of CIN 2/3 (25/28). CONCLUSION: HPV testing does not appear to add significantly to cytology in terms of positive predictive value or detection rate, if extended cytologic indications for colposcopy are used.     

子宫颈上皮内瘤变筛查方法的综合评价

目的　对宫颈上皮内瘤变 (CIN)筛查方法即宫颈涂片自动检测系统 (papnetcytologycomputertechnology ,CCT)和新柏氏程控超薄细胞检测系统 (thinpreppaptest,TPT)两种细胞学检查方法进行综合评价。方法　对因细胞学检查异常而行阴道镜下多点活组织检查 (活检 )及病理检查的 374例患者的临床资料进行回顾性分析。结果　细胞学检查诊断为炎症者 9 1% ,低度鳞状上皮内瘤变(LSIL) 4 3 3% ,高度鳞状上皮内瘤变 (HSIL) 2 0 3% ,可疑癌 1 9% ;经阴道镜下多点活检及病理检查 ,诊断为炎症者增加到 5 3 5 % ,CINⅠ减少到 17 9% ,CINⅡ、CINⅢ、原位癌占 2 5 4 % ,可疑早期浸润癌和浸润癌增加到 3 2 %。 2 5 4 %的细胞学不能明确诊断意义的不典型鳞状上皮病变中 ,5 2 6 % (5 0 /95 )为炎症或未见异常 ,4 7 4 % (45 /95 )为CINⅠ以上的病变。 374例患者中 ,行CCT检查者 188例 ,TPT检查者 186例 ,两种细胞学检查结果分别与阴道镜检查结果相比 ,TPT的符合率显著高于CCT(P<0 0 1)。细胞学检查诊断为LSIL及以下病变的符合率 (79 7% )显著高于诊断为HSIL以及癌变者的符合率 (2 0 3% ) ,两者比较 ,差异有显著性 (P <0 0 1) ,而两种细胞学检查方法间无差别。人乳头状瘤病毒 (HPV)感染的发生率为 34 0 % ,阴道镜检查的     

hrHPV E6/E7 mRNA用于宫颈癌机会性筛查的临床价值

目的:研究hrHPVE6/E7 mRNA在宫颈筛查中的准确性,探索其用于宫颈癌机会性筛查的临床价值。方法:选取2013年1月至2015年12月在青岛市市立医院及城阳区人民医院妇科门诊行机会性筛查的女性共7791例,年龄25~65岁。所有受试女性均行宫颈液基薄层细胞学检查(LBC)。每位受试者同时行HPV检测,根据采取的HPV方法不同分为3组:HC2组(2417例),HPV分型组(2456例),E6/E7组(2906例)。比较4种筛查方法的灵敏度、特异度、阳性预测值、阴性预测值、阴道镜转诊率、CINⅡ+/CINⅢ+检出率。结果:E6/E7检测CINⅡ+/CINⅢ+的灵敏度分别为93.02%和94.83%,NPV分别为99.52%和99.88%,与HC2及HPV分型之间无统计学差异(P0.05)。E6/E7检测CINⅡ+/CINⅢ+的特异度分别为90.20%和86.90%,与LBC、HC2及HPV分型两两比较均有统计学差异(P0.01)。以HC2和HPV分型为参照时,E6/E7检测CINⅡ+/CINⅢ+的RR均1。E6/E7的阴道镜转诊率为14.73%,低于另两种HPV检测方法,高于LBC,差异有统计学意义(P0.01)。3种HPV检测方法的CINⅡ+/CINⅢ+检出率无统计学差异(P0.05)。结论:hrHPV E6/E7 mRNA与HC2和HPV分型相比,灵敏度相同、特异度高,阴道镜转诊率低,CINⅡ+/CINⅢ+检出率无差别,可用于宫颈癌的机会性筛查。     

传统宫颈细胞学检查与薄层细胞学检测的分析比较与评价

目的　对子宫颈癌和癌前病变的检查方法进行综合分析比较与评价。方法　对 2 10 0例患者分别采用传统宫颈细胞涂片 (10 4 9例 )和新柏氏薄层细胞学检测系统 (Thinprepcytologictest,TCT 10 5 1例 )进行宫颈病变的早期筛查 ,对 2 0 6例细胞学阳性或临床可疑的患者行阴道镜下活组织检查。结果　TCT标本的不满意率(0 .4 8% )明显低于传统宫颈细胞涂片 (1 4 3% ) ,明显提高了子宫颈癌及癌前病变的阳性诊断率 ,降低了对AS CUS的诊断率。传统细胞学和TCT检查与阴道镜下活检病理结果符合率分别为LSIL :5 6 82 % (2 5 4 4 )和 74 36 %(2 9 39) ,HIS :4 5 4 5 % (5 11)和 85 71% (18 2 1) ,HPV感染的符合率分别为 5 3 5 7% (15 2 8)和 75 6 8% (2 8 37)。HPV感染和CIN的高发年龄分别为 2 0～ 30岁和 30～ 5 0岁。结论　宫颈细胞学筛查是子宫颈癌及癌前病变早期诊断的重要手段 ,TCT独特的取材与制片方法 ,更有利于宫颈阳性病变的检出 ;细胞学筛查异常或临床可疑的患者 ,应在阴道镜下多点活检 ;细胞学提示HPV感染者 ,应行病理和HPV -DNA检测证实。     

Liquid-based cytology and human papillomavirus testing: A pooled analysis using the data from 13 population-based cervical cancer screening studies from China

Objective

The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice.

Methods

A pooled analysis of liquid-based cytology (LBC) and HR-HPV testing using data from 13 population-based cervical cancer screening studies conducted in China was performed. Participants (n = 25,404) received LBC and HR-HPV testing. Women found to be positive on screening were referred for colposcopy and biopsy. The effectiveness of screening strategies that use: LBC with HR-HPV triage for atypical squamous cells of undetermined significance (ASC-US), HR-HPV testing with cytology triage for HPV positive tests, or LBC and HPV cotesting was compared with that of LBC screening alone.

Results

LBC with HR-HPV triage for ASC-US had similar sensitivity compared with LBC alone, but significantly increased specificity for both cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) endpoints, and had the best balance between sensitivity and specificity among the strategies. LBC and HR-HPV cotesting had the highest sensitivity and negative predictive value (NPV) and could permit a safe extension of screening intervals. Through the use of an immediate colposcopy threshold of ASC-US or worse for HR-HPV positive women and the use of a raised threshold of low-grade squamous intraepithelial lesion (LSIL) or worse for HR-HPV negative women, LBC and HR-HPV cotesting could provide the same effectiveness as LBC testing with HR-HPV triage for ASC-US at baseline tests.

Conclusions

The results of the current study support the use of the cervical cancer screening guidelines in China.     

Risk of Cervical Dysplasia After Colposcopy Care and Risk-Informed Return to Population-Based Screening: A Systematic Review

This systematic review examined the risk of cervical dysplasia among women who have undergone a colposcopy episode of care to inform their return to population-based cervical screening. PubMed, Embase, and grey literature were searched between January 2000 and 2018. One reviewer screened citations against pre-defined eligibility criteria. A second reviewer verified 10% and 100% of exclusions at title and abstract and at full-text screening, respectively. One reviewer extracted data and assessed methodological quality of included articles; a second reviewer verified these in full. The primary outcome was incidence of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) subsequent to initial colposcopy evaluation. Secondary outcomes included incidence of CIN2+ after negative follow-up test results and performance of follow-up strategies. Results were synthesized narratively. A total of 48 studies were included. The 1- to 5-year CIN2+ risks after colposcopy evaluation ranged from 2.4% to 16.5% among women treated for CIN2+ and from 0.7% to 16.8% among women untreated for CIN grade 1 or less (≤CIN1). Follow-up strategies included single or repeat cytology, human papillomavirus (HPV) testing, or combined HPV/cytology co-testing at various intervals. After negative follow-up test results, risk varied by follow-up strategy for both groups and by referral cytology severity for untreated women. Performance of follow-up strategies varied among treated women. Among untreated women, co-testing demonstrated greater sensitivity than cytology alone. In conclusion, women treated during colposcopy for CIN2+ and women with ≤CIN1 who were referred to colposcopy for low-grade cytology and who did not receive treatment may be able to return to population-based screening after negative co-testing results. Current evidence does not suggest that women untreated for ≤CIN1 who are referred for high-grade cytology be returned to screening at an average risk interval. The optimal strategy for colposcopy discharge needs ongoing evaluation as implementation of HPV testing evolves.     

阴道镜检查及HPV-DNA分型检测在HSIL患者诊断中的作用

目的 了解阴道镜检查和HPV-DNA分型检测在高度鳞状上皮内病变(HSIL)患者诊治中的作用。 方法 对2005年1月至2007年12月北京大学第一医院妇产科宫颈细胞学检测为HSIL的患者551例行阴道镜检查,对于镜下有异常发现者519例行多点活检,对于不满意的阴道镜检查,多点活检同时加宫颈管诊刮术,分析单次阴道镜检查检出CIN2及以上级别病变(≥CIN2)的情况,并对其中376例同时行HPV-DNA分型检测的结果进行分析。 结果 551例HSIL患者中,阴道镜下多点活检检出CIN 1 患者58例(10.5%);CIN2、3患者344例(62.4%);宫颈浸润癌11例(2.0% )。<30岁、30~39岁、40~49岁、50~59岁和>60岁不同年龄组检出率比较,差异有统计学意义(P=0.034)。376例有HPV-DNA分型的HSIL患者中, HPV-DNA高危亚型感染率为87.5%,其中 16亚型感染占第一位(45.7%);在HR-HPV 阳性组尤其是HPV-16亚型阳性组,检出≥CIN2与HR-HPV阴性组比较,差异有统计学意义(P=0.000)。 结论 在HSIL患者中,经单次阴道镜检查仅检出62.4%的≥CIN2患者,HPV-DNA分型检测可增加阴道镜的检出率,对于单次阴道镜检查未发现异常的HSIL患者应给予重视。     

Prevalence of human papilloma virus infection of the uterine cervix in women with abnormal cervical cytology

PURPOSE OF INVESTIGATION: To determine the prevalence of human papillomavirus (HPV) using polymerase chain reaction (PCR) in women with abnormal cytology results. METHODS: A prospective study of 215 women with abnormal cytology results referred consecutively to the cervical pathology clinic was carried out. A second cervical cytology using the Bethesda System was performed on all the patients to confirm the initial diagnosis, as well as to test for the presence of HPV by PCR and a colposcopy and punch biopsy in cases presenting with an abnormal pattern on colposcopy. The sensivitiy, specificity, and positive and negative predictive value (PPV and NPV) were calculated using 2 x 2 tables. RESULTS: The women aged 35 years or younger presented a higher percentage of HPV infection (85.6%) than the women over 35 years of age (54%). The highest percentage of women with a positive result for HPV was found in those with a cytological high-grade squamous intraepithelial lesion (HSIL) (85.5%), as compared with 47.4% of the women with a cytological low-grade squamous intraepithelial lesion (LSIL). HPV infection has a high negative predictive value (93.2% of cases) and a high sensitivity (93.5%) for the detection of HSIL by biopsy, although the specificity and positive predictive value were low, 51.5% and 52.1%, respectively. CONCLUSION: Patients with cytological HSIL have a high prevalence of HPV infection.     

Screening for cervical cancer in high-risk populations: DNA pap test or Hybrid Capture II test alone?

This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system. Women with suspected cervical disease were included in this cross-sectional study at a tertiary center in S?o Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as "gold standard" and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy.     

人乳头瘤病毒L1壳蛋白在筛查宫颈鳞状上皮内病变中的应用

目的:探讨人乳头瘤病毒(HPV)L1壳蛋白筛查HPV阳性妇女宫颈脱落细胞中宫颈鳞状上皮内病变的应用价值。方法:选取2012年5月至2014年12月就诊于温州市人民医院的妇女212例,收集宫颈脱落细胞并行HPV L1壳蛋白检测、HPV DNA分型、TCT(液基细胞学)及阴道镜下活检,比较HPV阳性妇女的宫颈脱落细胞中HPV L1壳蛋白的表达情况。结果:212例细胞学标本中HPV L1壳蛋白阳性率为33.9%,其中未见上皮内病变/恶性细胞组(NILM)、无明确诊断意义的鳞状上皮细胞病变组(ASCUS)、低度鳞状上皮内病变组(LSIL)、不能排除高度鳞状上皮内病变组(ASC-H)、高度鳞状上皮内病变组(HSIL)中阳性率分别为47.1%、35.1%、54.2%、29.2%、16.1%,各组比较差异有统计学意义(P0.05);两两比较,HSIL组与LSIL组和NILM组比较,差异均有统计学意义(P均0.005);进行数据合并后,LSIL/ASCUS组与ASC-H/HSIL组比较差异有统计学意义(P=0.001)。178例宫颈细胞学异常患者中,宫颈低级别病变和宫颈高级别病变的HPV L1壳蛋白阳性率比较,在ASCUS组(P=0.000)、LSIL组(P=0.004)中均有差异,在ASC-H组(P=0.127)、HSIL组(P=0.515)中均无差异。HPV 16/18感染患者的HPV L1壳缺失同宫颈高级别病变有更紧密的关系(P=0.003)。结论:子宫颈脱落细胞HPV L1壳蛋白检测在HPV阳性妇女的子宫颈病变筛查中具有一定的价值,可能成为一种合适的分流方法。     

Significance of atypical cervical cytology in pregnancy.

To ascertain the significance of squamous atypia encountered during routine Papanicolaou smear screening in pregnancy, we reviewed our experience with 76 pregnant women seen during a 4-year period. All were evaluated with repeat cytology and colposcopy during pregnancy and again postpartum. Colposcopic examination during pregnancy revealed a normal transformation zone without evidence of intraepithelial neoplasia in 46 women. In six of these women, repeat cytology was interpreted as cervical intraepithelial neoplasia (CIN) grade 1. In 30 women, an abnormal transformation zone was identified--14 with a negative repeat cytology. In five women, the transformation zone was interpreted as compatible with CIN 2 or CIN 3. Colposcopically directed biopsies were performed in 31 women, in all but two postpartum. Of the 76 women, human papilloma virus or CIN was identified on biopsy in 16 women (21%). We propose that an isolated report of atypical squamous cells on cervical cytology obtained at the initial prenatal visit does not warrant colposcopic evaluation during pregnancy, unless a repeat cytology suggests CIN. Repeat cytology and evaluation to exclude infections and inflammatory lesions is appropriate. However, if a subsequent cytology is abnormal, postpartum colposcopy and colposcopically directed biopsies seem appropriate, since the prevalence of HPV or CIN was 21%.     

p16/Ki-67双染在宫颈癌及癌前病变初筛中的应用价值研究

目的:评价采用p16/Ki-67双染检测技术作为宫颈癌及癌前病变初筛方法的效果及应用价值。方法:对重庆市万州区982例年龄35~64岁有性生活的妇女进行宫颈癌筛查。每位妇女均接受了人乳头瘤病毒DNA(HPV DNA)检测、Thin Prep液基细胞学检查、p16/Ki-67双染检测,对结果异常者进行阴道镜检查,阴道镜下在可见病变处直接取活检,无可见病变时,行宫颈管搔刮术(ECC)。比较3种方法分别作为初筛手段识别宫颈癌前病变(高级别鳞状上皮内病变)及浸润癌的灵敏度、特异度、阳性预测值和阴性预测值等指标,以受试者工作特征(ROC)曲线下面积(AUC)综合分析3种方法作为宫颈癌初筛手段的应用价值。结果:最终966例妇女进入研究,共检出高级别鳞状上皮内病变及浸润癌患者42例。HPV DNA检测、液基细胞学检查和p16/Ki-67检测对宫颈癌及癌前病变患者的灵敏度分别为97.6%、88.1%、92.9%;特异度分别为84.1%、78.8%、82.8%;阳性预测值分别为21.8%、15.9%、19.7%;阴性预测值分别为99.9%、99.3%、99.6%。p16/Ki-67检测的AUC分别与HPV DNA检测、液基细胞学检查相比,差异均无统计学意义(P0.05)。结论:p16/Ki-67双染检测初筛宫颈癌及癌前病变的效果与HPV DNA检测及液基细胞学检查相似,因其具有简便、客观、高效、易于重复的特点,p16/Ki-67双染检测为宫颈癌及癌前病变的有效初筛提供了一种新选择。     

贵州省三都水族自取样HPV检测宫颈癌筛查及分流模式#br#

Objective?To explore a cervical cancer screening strategy suitable for remote minority areas in China. Methods?A total of 1 874 cases of shui minority women aged 21~65 years in Sandu were randomly sampled self-sampling HPV test, TCT test and P16 cytological immunohistochemical test. The patients with HPV positive, TCT abnormality (ASC-US) and P16+underwent colposcopy and biopsy, and squamous intraepithelial lesion (SIL) was detected. Results?The positive rate of HR-HPV was 15.69% in 1 874 women. HPV52 was the most common type, followed by HPV16, HPV39, HPV58 and HPV56. Among 249 patients with colposcopy biopsy, 23 cases (9.24%) were detected with HSIL or above lesions.The positive rates of p16 in HSIL and above cervical lesions, LSIL and cervicitis were 73.91%, 34.57% and 10.34% (P<0.001).The sensitivity of self-sampled HPV test to HSIL+ was 100%, and the area under ROC curve for HSIL+ detected by HPV-positive test and p16 test was 0.577 (P>0.05) and 0.774 (P<0.05), respectively. Conclusion?Self-sampled HPV was highly sensitive to HSIL. Using self-sampling HPV detection as primary screening, combined with p16 staining triage, can be used as a screening strategy in remote areas of Guizhou province to improve the coverage of screening.     

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.     

The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil)

Abstract. Lorenzato F, Ho L, Terry G, Singer A, Santos LC, de Lucena Batista R, Lubambo T. The use of human papillomavirus in detection of cervical neoplasia in Recife (Brazil).
High risk types of human papillomavirus (HR-HPV) play a major role in cervical cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and typing as a means of identifying cervical neoplasia in a high risk population. A management algorithm for implementation of HPV detection in clinical practice is also proposed. A nested case-control within a cohort study was undertaken in Recife (Brazil). All 479 participants had cervical scrapes collected for HPV detection followed by colposcopy. Samples were blindly analyzed by polymerase chain reaction (PCR) and typed by restriction fragment length polymorphism (RFLP).
HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman screened in this study and is significantly better than cytology in identifying women at risk of developing cervical cancer ( P = 0.0001). Women who tested positive for HR-HPV had over 35-fold increased risk of having high grade squamous intraepithelial lesion (HSIL) or cervical cancer, although this does not necessarily translate into the same risk rate for women with latent HPV infection developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85% specificity for cervical cancer detection. In combination with cytology it provides a negative predictive value of 99.4% and a sensitivity of over 96% for detection of HSIL and cervical cancer.
We conclude that HPV typing is an inexpensive and effective method for identification of cervical neoplasia and women at risk of developing it. It improves quality control for both false negative and false positive cytology results. Routine screening intervals could safely be increased to 3–5 years, decreasing anxiety and socio-economic inconveniences.