高危型人乳头状瘤病毒DNA检测方法在宫颈疾病中的临床意义

目的 评价高危型人乳头状瘤病毒DNA(酶切信号放大法)(Cervista High-risk humanpapilloma vires,Cervista HR-HPV)检测方法在宫颈疾病中的临床意义.方法 利用Cerrista HR-HPV检测方法对437例人组标本进行高危型HPV检测,检测结果与基因测序结果进行对比,同时评价Cervista HR-HPV检测方法在检测CIN2以上的宫颈病变(CIN 2+CIN 3+Cancer,以下简称CIN2+)的能力,以及三组A5/A6,A7,A9与CIN2+的相关性.结果 Cervista HR-HPV检测方法与基因测序结果相比总体符合率为88.26%,基因测序阳性率为29.08%,本实验为38.96%(P<0.0001).该检测方法对CIN2+灵敏度98.46%.特异度58.49%.阳性预测值29.68%,阴性预测值99.54%.A9和CIN2+的95%OR值的可信区间为10.086～57.283(P<0.0001).结论 Cervista HR-HPV与基因测序的检测一致性较好.对于CIN2+灵敏度与特异性较好,可以应用于宫颈癌的防癌筛查,出现A阳性的患者建议进一步行阴道镜检测确诊是否有CIN2+.     

高危型人乳头状瘤病毒DNA检测方法在宫颈疾病中的临床意义

目的 评价高危型人乳头状瘤病毒DNA(酶切信号放大法)(Cervista High-risk humanpapilloma vires,Cervista HR-HPV)检测方法在宫颈疾病中的临床意义.方法 利用Cerrista HR-HPV检测方法对437例人组标本进行高危型HPV检测,检测结果与基因测序结果进行对比,同时评价Cervista HR-HPV检测方法在检测CIN2以上的宫颈病变(CIN 2+CIN 3+Cancer,以下简称CIN2+)的能力,以及三组A5/A6,A7,A9与CIN2+的相关性.结果 Cervista HR-HPV检测方法与基因测序结果相比总体符合率为88.26%,基因测序阳性率为29.08%,本实验为38.96%(P<0.0001).该检测方法对CIN2+灵敏度98.46%.特异度58.49%.阳性预测值29.68%,阴性预测值99.54%.A9和CIN2+的95%OR值的可信区间为10.086～57.283(P<0.0001).结论 Cervista HR-HPV与基因测序的检测一致性较好.对于CIN2+灵敏度与特异性较好,可以应用于宫颈癌的防癌筛查,出现A阳性的患者建议进一步行阴道镜检测确诊是否有CIN2+.     

高危型人乳头状瘤病毒DNA检测方法在宫颈疾病中的临床意义

目的评价高危型人乳头状瘤病毒DNA（酶切信号放大法）（Cervista High-risk humanpilloma virus,CervistaHR-HPV）检测方法在宫颈疾病中的临床意义。方法利用CervistaHR-HPV检测方法对437例人组标本进行高危型HPV检测,检测结果与基因测序结果进行对比,同时评价CervistaHR-HPV检测方法在检测CIN2以上的宫颈病变（CIN2＋CIN3＋Cancer,以下简称CIN2＋）的能力,以及三组A5／A6,A7,A9与CIN2＋的相关性。结果CervistaHR-HPV检测方法与基因测序结果相比总体符合率为88．26％,基因测序阳性率为29．08％,本实验为38．96％（P（0．0001）。该检测方法对CIN2＋灵敏度98．46％,特异度58．49％,阳性预测值29．68％,阴性预测值99．54％。A9和CIN2＋的95％OR值的可信区间为10．086～57．283（P〈0．0001）。结论CervistaHR-HPV与基因测序的检测一致性较好,对于CIN2＋灵敏度与特异性较好．可以应用于宫颈癌的防癌筛查,出现A阳性的患者建议进一步行阴道镜检测确诊是否有CIN2＋。     

Clinical performance of the CLART human papillomavirus 2 assay compared with the hybrid capture 2 test

Persistent infection by high‐risk human papillomavirus (HR‐HPV) is a cause of cervical cancer. The use of HPV detection in cervical screening programs may improve the ability to identify women at risk of cervical cancer. Therefore, the development of appropriate methods for the detection of HR‐HPV is essential. The aim of this study was to evaluate the clinical performance of the CLART Human Papillomavirus 2 assay (CLART) in comparison with the Hybrid Capture 2 test (HC2), using a clinical cut‐off of cervical intraepithelial neoplasia grade 2 or worse. Discrepant results were analyzed further by the PapilloCheck HPV genotyping system. In the 425 studied women, HR‐HPV positivity rates were similar by both tests (CLART‐13 HR‐HPV: 63.1%; CLART‐17 HR‐HPV: 64.7%; HC2: 64.5%). Agreement between CLART‐13 HR‐HPV (κ = 0.969; concordance level 98.6%), CLART‐17 HR‐HPV (κ = 0.974; concordance level 98.8%), and HC2 were very good. When 13 HR‐HPV types were considered, the two tests showed a clinical sensitivity of 96% (95% CI: 92.6–97.9). The clinical specificity of CLART‐13 HR‐HPV was 73.6% (95% CI: 66.7–79.5) for cervical intraepithelial neoplasia grade 2 or worse, which was comparable to HC2 (71.4%; 95% CI: 64.3–77.5). When all 17 HR‐HPV types were considered, CLART showed a clinical sensitivity of 96.9% (95% CI: 93.8–98.5) and a clinical specificity of 71.9% (95% CI: 64.9–78.0). In conclusion, the CLART assay is efficient, sensitive, reproducible, and has a similar performance to HC2 for cervical intraepithelial neoplasia grade 2 or worse. Furthermore, this assay has the advantage of detecting and genotyping 35 HPV types by a single test, which can provide additional information on the predictive value of infection with HR‐HPV. J. Med. Virol. 83:272–276, 2011. © 2010 Wiley‐Liss, Inc.     

Comparison of clinical performance of Abbott RealTime High Risk HPV test with that of hybrid capture 2 assay in a screening setting

Randomized trials have produced sound evidence about the efficacy of screening with human papillomavirus (HPV) DNA tests in reducing cervical cancer incidence and mortality. We evaluated the clinical performance and reproducibility of the Abbott RealTime High Risk (HR) HPV test compared with that of the HR hybrid capture 2 (HC2) assay as assessed by a noninferiority score test. A random sample of 998 cervical specimens (914 specimens of cervical intraepithelial neoplasia less severe than grade 2 [相似文献   

Cervista HR and HPV 16/18 assays vs hybrid capture 2 assay: outcome comparison in women with negative cervical cytology

Sensitive and specific assays for human papillomavirus (HPV) are essential for patient management. In this study, we directly compared the efficacy of the Hybrid Capture 2 (HC2; Qiagen, Valencia, CA) and Cervista assays (Hologic, Madison, WI). Consecutive cervical cytology specimens (n = 601) were tested using HC2, Cervista HR, and Cervista HPV 16/18 with analysis of only cytology-negative cases (n = 533). Results indicated no significant difference (P = .458) in prevalence rates between HC2 (7.5%) and Cervista HR (8.5%). The Cervista 16/18 prevalence was 1.6%. The negative percentage of agreement was 95.1% (468/492) vs a 70% (28/40) positive percentage of agreement. No false-negative results were detected by the Cervista internal DNA control. Our data show 29 discordant positive results (12 HC2 and 17 Cervista HR), suggesting some women with negative cytology may be triaged for unnecessary follow-up with either assay. For clinical screening, Cervista HR and HC2 are comparable and, by extension, should provide excellent negative predictive value for histologically relevant disease.     

Clinical Validation of the Cervista HPV HR Test According to the International Guidelines for Human Papillomavirus Test Requirements for Cervical Cancer Screening

This study demonstrates that both the clinical sensitivity and specificity of the Cervista HPV HR test for high-risk human papillomavirus (HPV) detection are not inferior to those of the Hybrid Capture 2 (HC2) test. The intra- and interlaboratory reproducibilities of Cervista were 92.0% (kappa, 0.83) and 90.4% (kappa, 0.80), respectively. The Cervista HPV HR test fulfills all the international HPV test requirements for cervical primary screening purposes.     

Comparison of the Digene Hybrid Capture 2 assay and Roche AMPLICOR and LINEAR ARRAY human papillomavirus (HPV) tests in detecting high-risk HPV genotypes in specimens from women with previous abnormal Pap smear results

The development of cervical cancer is strongly associated with the presence of persistent high-risk (HR) human papillomavirus (HPV) infection. Recently, the commercially manufactured PCR-based Roche AMPLICOR (AMP) and LINEAR ARRAY (LA) HPV tests have become available for HPV detection. However, knowledge of their clinical performance compared to the U.S. Food and Drug Administration-approved Hybrid Capture 2 (HC2) assay is limited. This study evaluated the concordance between the HC2, AMP, and LA tests in detecting HR-HPV among a cohort of 1,679 women with previous abnormal Pap smear results. Overall, 1,393 specimens (81.3%) generated concordant results for HR-HPV presence or absence by the three assays. The concordance levels were substantial between the HC2 and AMP tests (84.4%, kappa = 0.6419) and between the HC2 and LA tests (84.0%, kappa = 0.6341) and nearly perfect between the AMP and LA tests (97.8%, kappa = 0.9441). HR-HPV prevalence, as detected by the AMP or LA tests, was significantly higher among women with cytological or histological high-grade disease (CIN2 or greater) than that detected by HC2 (P < 0.0001). The AMP and LA tests exhibited greater sensitivity, but lower specificity, than HC2 for detecting HR-HPV among this cohort of women with underlying cervical abnormalities, particularly among subjects with histologically proven high-grade disease. Both PCR-based HPV tests may be valuable in the management of care for women with underlying cervical abnormalities, in predicting treatment success, and in studying the clearance or acquisition of new infections.     

Comparison of Commercial Hybridization and Automated Transcription-Mediated Amplification Modalities for Detection of High-Risk Human Papillomavirus Nucleic Acid

Assessment of 4,056 cytology collections by Cervista HPV HR and APTIMA HPV yielded 88.7% concordance, with increased detection by Cervista in patients with atypical squamous cells of undetermined significance (ASC-US) and patients negative for intraepithelial lesions and malignancy (NILM) (P ≤ 0.02). Both assays detected ≥91.7% of cervical intraepithelial neoplasia grade 2+ (CIN2+) lesions. A total of 262 specimens demonstrated luminescence within all three Cervista oligonucleotide mixtures (triple positive). APTIMA HPV and PCR-based microarray confirmed triple-positive results at rates of 7.3% and 5.9%, respectively.     

HIGH‐RISK HPV testing as the primary screening method in an organized regional screening program for cervical cancer: the value of HPV16 and HPV18 genotyping?

Since 2012, testing high‐risk (HR)HPV has been used as the primary screening test for women ≥35 years attending the organized cervical cancer screening program in the city of Tampere. We evaluated the contribution of HPV16/18 genotyping. Data from 2012 and 2013, and the follow‐up samples in 2013 and 2014, respectively, were analyzed. Abbott RealTime High‐Risk HPV test detecting 14 HRHPV genotypes combined with concurrent genotyping for HPV16 and HPV18 was used. HPV was positive in 794 samples out of 11 346 HPV tested women (7%). HPV16/18 was represented in 22% of HPV‐positive cases. Negative cervical cytology (NILM) was reported in 51% of HPV‐positive samples. HPV16/18 genotype was accompanied with 50% of HSIL/ASC‐H cases. The predominance of HPV16/18 in higher grade lesions was even more evident in cervical biopsies as 57% of CIN3 cases were associated with HPV16/18, and only 20% of carcinomas were associated with nonspecified high‐risk (NSHR) genotypes. In agreement with previous studies HPV16/18 genotypes caused higher grade cytological and histological changes/pathologies than NSHR genotypes in primary screening. Nevertheless, the majority of HRHPV genotypes detected in the screened population were nonHPV16/18, and especially within persistent infections, precancerous lesions were found also among women with NSHR genotypes.     

Human papillomavirus (HPV) E6/E7 mRNA as a triage test after detection of HPV 16 and HPV 18 DNA

High‐risk human papillomavirus (HPV) DNA detection provides high sensitivity but low specificity for moderate‐grade cervical intraepithelial neoplasia or worse histological identification. A prospective study evaluated mRNA testing efficacy for predicting this histological diagnosis in case of HPV 16 and/or 18 DNA detection. A total of 165 endocervical samples harboring HPV 16 and/or 18 DNA were tested with NucliSENS‐EasyQ® HPV E6/E7‐mRNA‐assay (Biomerieux, Marcy l´Etoile, France). Women with cytological alterations were referred to colposcopy (n = 111). Moderate‐grade cervical intraepithelial neoplasia or worse was diagnosed in 25.8% of women presenting atypical squamous cells of undetermined significance or low‐grade squamous intraepithelial lesions and in 89.8% of women with high‐grade squamous intraepithelial lesions. mRNA sensitivity was 81.3% and 84.1%, respectively. Specificity was 52.2%, and 80.0%, respectively. Negative predictive value (NPV) was 88.9% in undetermined or low‐grade squamous lesions. Positive predictive value (PPV) was 97.4% in high‐grade squamous lesions. mRNA reduced colposcopies by 44.3% in undetermined or low‐grade squamous lesions. Direct treatment of mRNA‐positive cases reduced 77.5% of colposcopies in high‐grade squamous lesions. Women without cytological alterations were followed for 18 months (n = 35), and moderate‐grade cervical intraepithelial neoplasia or worse was diagnosed in 34.3%; mRNA sensitivity and specificity were 83.3% and 86.9%, respectively. PPV and NPV were 76.9% and 90.9%, respectively for predicting moderate‐grade cervical intraepithelial neoplasia or worse in 18 months. mRNA reduced the number of visits for follow‐up in 62.2%. In conclusion, NucliSENS‐EasyQ® HPV E6/E7‐mRNA‐assay (Biomerieux) can serve as a triage test in case of HPV 16 and/or 18 DNA detection. J. Med. Virol. 85: 1063–1068, 2013. © 2013 Wiley Periodicals, Inc.     

Comparative evaluation of nm23 and p16 expression as biomarkers of high-risk human papillomavirus infection and cervical intraepithelial neoplasia 2(+) lesions of the uterine cervix

Benevolo M, Terrenato I, Mottolese M, Marandino F, Muti P, Carosi M, Rollo F, Ronchetti L, Mariani L, Vocaturo G & Vocaturo A
(2010) Histopathology 57 , 580–586
Comparative evaluation of nm23 and p16 expression as biomarkers of high‐risk human papillomavirus infection and cervical intraepithelial neoplasia 2⁺ lesions of the uterine cervix Aims: To investigate the clinical role of nm23 expression in identifying both high‐risk human papillomavirus (HR‐HPV) and high‐grade cervical lesions or carcinomas [cervical intraepithelial neoplasia 2⁺ (CIN2⁺)], and to compare it with p16 overexpression, as this latter biomarker has already been reported widely in HR‐HPV infected cervical lesions. Methods and results: Immunohistochemical evaluation of nm23 and p16 in 143 cervical biopsy specimens including negative, low‐ and high‐grade lesions and squamous carcinomas (SC). HR‐HPV testing by Digene hybrid capture 2 (HC2) and polymerase chain reaction (PCR) on the cervico‐vaginal samples of the same patients. In detecting CIN2⁺, p16 was significantly more sensitive and specific than nm23 (96.3% versus 81.8% and 66% versus 36.4%, respectively, both P < 0.0001). Concerning HR‐HPV detection by HC2, p16 showed a significantly higher specificity than nm23 (82% versus 47%, P <0.0001), although the sensitivities were comparable (71% versus 76%). We found a significantly direct correlation between nm23 and HC2 findings. However, nm23 expression did not correlate with HPV16/18 infection. In contrast, we observed a significant association between p16 overexpression and HPV16/18 genotypes. Conclusions: We confirm the diagnostic value of p16 overexpression. Moreover, despite in vitro data regarding the interaction with the HPV‐E7 protein, nm23 does not appear to be a more useful biomarker than p16 in identifying CIN2⁺ or HR‐HPV infection.     

Comparison of the Anyplex II HPV28 assay with the Hybrid Capture 2 assay for the detection of HPV infection

BackgroundHuman papillomavirus (HPV) testing is an important part of cervical cancer screening and management of women with abnormal cytology results. The Hybrid Capture 2 (HC2) has been recommended for use as a reference test.ObjectiveTo evaluate a new real-time PCR assay (Anyplex II HPV28) for detecting high risk (HR) HPV and to compare it to the HC2. In addition, we compared the genotyping results of the Anyplex II HPV28 to those of sequencing analysis.Study designA total of 1114 cervical swab specimens were consecutively obtained from a single healthcare center. We submitted all specimens for HPV detection with Anyplex II HPV28 and HC2, then analyzed the discordant results using multiplex PCR followed by direct sequencing.ResultsHC2 detected 72 (6.5%) cases with HR HPV, while Anyplex II HPV28 identified 138 (12.4%) cases. The overall agreement rate was 91.4% (1018/1114) of cases. Discordant results between these two assays were observed in 96 cases; 15 were positive only by HC2, and 81 were positive only by Anyplex II HPV28. Sequencing analyses performed in 80 cases of discordant results revealed 11 false-positive, and 67 false-negative results using HC2 tests and two false-positive results using Anyplex II HPV28.ConclusionsThe Anyplex II HPV28 assay is analytically more sensitive in the detection of the 13 HR types represented by the HC2 assay and exhibited a higher concordance with comprehensive genotyping based on the sequencing analysis, and it could be used as a laboratory testing method for identifying HPV genotypes.     

Comparison of Abbott RealTime High Risk HPV and Hybrid Capture 2 for the detection of high-risk HPV DNA in a referral population setting

Background

The Abbott RealTime High Risk HPV assay (ART) is an automated multiplex real-time PCR test for detection of DNA from 14 high risk (HR) HPV types in cervical specimens and simultaneous distinction of HPV16 and HPV18 from other HR-HPV.

Objectives

To evaluate the performance of the ART assay in specimens referred for HPV testing to our laboratory (referral population) by comparison with historical data from HC2 and INNO-LiPA as well as histological status, if available.

Study design

412 cervical specimens were collected from women between 18 and 70 years of age: 301 previously tested by HC2 without clinical data and 111 previously tested by HC2 and INNO-LiPA with histological diagnosis of CIN3+.

Results

Our study demonstrated good overall agreement between ART, HC2 and INNO-LiPA. In the group of the CIN3+ specimens HR-HPV was detected by ART in 93.07% (95% CI: 88.12-98.02), while HR-HPV detection rates with HC2 and INNO-LiPA were 91.09% (95% CI: 85.53-96.65) and 95.05% (95% CI: 90.82-99.28), respectively. The typing capability of ART for HPV16, HPV18 and a pool of twelve other HR-HPV types was investigated by comparison with INNO-LiPA demonstrating high overall assay concordance (89.81%; k 0.87).

Conclusions

The Abbott RealTime assay showed similar clinical performance for detection of CIN3+ compared with HC2. The high level of automation and ability to identify HPV16, HPV18 and other HR-HPV make this assay a very attractive option for HR-HPV testing, potentially improving patient management by risk stratification of cytological abnormal populations.     

Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany

Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2+ (CIN2+), including 43 women with CIN3+. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2+ (P = 0.180) or CIN3+ (P = 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (<CIN2) and positive predictive value (CIN2+) of the AHPV test were significantly higher (both P < 0.001) than those of the HC2 test. The overall agreement between the tests was substantial (κ = 0.77). Finally, we present results for several possible triage strategies, based on the primary screening test being either the AHPV test or the HC2 test. In summary, the AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be used in primary cervical cancer screening for women ≥30 years of age.     

Clinical performance of Abbott RealTime High Risk HPV test for detection of high-grade cervical intraepithelial neoplasia in women with abnormal cytology

BackgroundAbbott RealTime High Risk (HR) HPV is a recently developed test for the detection of 14 high-risk oncogenic HPV types combined with the ability to concurrently identify genotypes 16 and 18.ObjectivesThe clinical performance of the Abbott RealTime HR HPV test was evaluated in comparison with the Hybrid Capture 2 (HC2) test for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). The relative accuracy of the Abbott RealTime HR HPV to detect high-risk HPV was also determined.Study designCervical specimens were collected from 702 patients with abnormal cytology who were referred for colposcopy, and were tested with liquid based cytology (LBC), Abbott RealTime HR HPV and HC2. Genotyping was done using the Linear Array (LA) method. Histological assessment was used as the gold standard for disease status. Clinical performance for detection of disease was evaluated for Abbott RealTime HR HPV in comparison with HC2 in the overall population and in each cytological grade. The relative accuracy for detection of high-risk HPV was assessed by concordance between the two tests and based on LA genotyping.Results and ConclusionsThe Abbott RealTime HR HPV showed similar clinical performance for detection of CIN2+ when compared with HC2, for both the overall population and those with a cytological grade of atypical squamous cells of undetermined significance (ASC-US). The accuracy for detection of high-risk HPV was significantly higher with Abbott RealTime HR HPV than with HC2.     

Comparison of the Digene HC2 assay and the Roche AMPLICOR human papillomavirus (HPV) test for detection of high-risk HPV genotypes in cervical samples

Many different methods with different sensitivity and specificity have been proposed to detect the presence of high-risk human papillomavirus (HR HPV) in cervical samples. The HC2 is one of the most widely used. Recently, a new standardized PCR-based method, the AMPLICOR HPV test, has been introduced. Both assays recognize the same 13 HR HPV genotypes. The performances of these two commercially available assays were compared in 167 consecutive women (for a total of 168 samples) who presented at the Colposcopy Clinic either for a follow-up or for a diagnostic visit. Concordant results were found in 140/168 cervical samples (overall agreement, 83%; Cohen's kappa = 0.63). Twenty-eight samples gave discordant results: 20 were positive with the AMPLICOR HPV test and negative with the HC2 assay, and 8 were negative with the AMPLICOR HPV test and positive with the HC2 assay. The genotyping showed that no HR HPV was detected in the 8 HC2 assay-positive AMPLICOR HPV test-negative samples, while in 8/20 AMPLICOR HPV test-positive HC2 assay-negative samples, an HR HPV genotype was found. The AMPLICOR HPV test scored positive in a significantly higher percentage of subjects with normal Pap smears. All 7 cervical intraepithelial neoplasia grade 3 patients scored positive with the AMPLICOR HPV test, while 2 of them scored negative with HC2. Both tests had positive results in the only patient with squamous cell carcinoma. In conclusion, this study shows that the HC2 assay and the AMPLICOR HPV test give comparable results, with both being suitable for routine use. The differences noted in some cases may suggest a different optimal clinical use.     

Comparison of Digene Hybrid Capture 2, GeneMatrix PapilloScreen,and a PCR sequencing assay in detecting high-risk and probable high-risk oncogenic HPV genotypes in specimens from Korean women

Most cervical cancers are caused by 15 high-risk (HR) and three probable high-risk (pHR) oncogenic types of human papillomavirus (HPV). However, current commercial HR HPV screening test products do not include pHR HPV genotypes. Recently, PapilloScreen has been developed to detect the 15 HR and three pHR HPV types. In this study, we evaluated the concordance levels and clinical performance of Hybrid Capture 2 (HC2), PapilloScreen, and a PCR sequencing assay in detecting HR and pHR HPV. The PapilloScreen (96.8 %) and PCR sequencing assay (96.8 %) demonstrated higher sensitivity than HC2 (80.7 %) for detecting HR and pHR HPV. The three assays showed similar specificities and positive or negative predictive values. The concordance levels were 86.5 % (κ = 0.68) and 86.5 % (κ = 0.67) between HC2 and PapilloScreen and between HC2 and PCR sequencing, respectively. A near-perfect concordance was observed between PapilloScreen and PCR sequencing (97.8 %, κ = 0.95). Overall, the agreement between the three assays suggests that the results obtained by the HC2 assay are more often discordant (12.6 %) than the PCR-based tests. In conclusion, PapilloScreen is highly sensitive for detecting high-grade CIN or cervical cancer. The PapilloScreen assay should be considered an accurate and sensitive method for detecting HR and pHR HPV infections and an epidemiological tool for prevalence studies as well as early diagnosis and intervention in HR and pHR HPV infections.     

Triage of cervical cytological diagnoses of atypical squamous cells by DNA methylation of paired boxed gene 1 (PAX1)

Detection of cervical high‐grade squamous intraepithelial lesions (HSIL) in patients with equivocal cytological abnormalities, such as atypical squamous cells (ASC) of undetermined significance (ASCUS) or inability to exclude high‐grade squamous intraepithelial lesions (ASC‐H) is still a challenge. This study tested the efficacy of PAX1 methylation analysis in the triage of cervical ASCUS and ASC‐H and compared its performance with Hybrid Capture 2 (HC2) HPV test. A hospital‐based case–control study was conducted. Cervical scrapings from patients with ASCUS or ASC‐H were used for the quantitative methylation analysis of PAX1 methylation by MethyLight and HPV testing by HC2. Patients with ASC‐H or ASCUS with repeated abnormal smears underwent colposcopic biopsy and subsequent therapies. Diagnoses were made by histopathology at a follow‐up of 2 years. The efficacies of detecting high‐grade lesions were compared. Fifty‐eight cervical scrapings with cytological diagnosis of ASCUS (n = 41) and ASC‐H (n = 17) were analyzed. One of the 41 (2.4%) ASCUS patients and seven of 17 (41.2%) ASC‐H patients were confirmed to have HSIL. After dichotomy of the PMR, PAX1 methylation rates were significantly higher in ASC developing HSIL compared with those developing reactive atypia (87.5% vs. 12.5%, P < 0.001). Testing PAX1 methylation in cervical swabs of patients with ASC confers better sensitivity (87.5% vs. 62.5%) and specificity (98.0% vs. 86.0%) than HC2 HPV testing. We show for the first time that PAX1 hypermethylation analysis may be a better choice than HC2 in the triage of ASCUS and ASC‐H. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

The clinical performance of human papillomavirus genotyping using PANArray HPV chip: Comparison to ThinPrep cytology alone and co-testing

Recently, a high-risk human papillomavirus (HR-HPV) detecting assay alone could be used as a first-line screening tool for cervical cancer, although the test system has been limited to the Cobas 4800 HPV test. However, the screening efficiency of the HPV chip, which is widely used in Eastern Asia because of the high prevalence of non16/18 HR-HPV genotypes, has not been well elucidated. After selecting 300 women who were co-tested using the PANArray HPV chip and the ThinPrep assay and had confirmed histological diagnoses, we evaluated the diagnostic accuracy of the PANArray HPV test based on direct sequencing and clinical performance compared to the ThinPrep alone and co-testing. HR-HPVs were identified in 212 (70.7 %) patients by the PANArray HPV test. The results of the PANArray HPV test and direct sequencing for detecting HR-HPVs were in almost perfect agreement, consistent in 95.3 % of the cases (k = 0.89). HR-HPVs were more commonly detected by the PANArray HPV assay in patients with high-grade squamous intraepithelial lesions (HSILs) or worse (p < 0.001, both) by cytological and histological examinations. The PANArray HPV test had higher sensitivity (91.7 %) than the ThinPrep (52.6 %) but co-testing increased the sensitivity for predicting HSIL or worse cervical lesions to 99.2 %. In conclusion, the PANArray HPV test accurately detected HR-HPVs determined by cytological and histological examinations to be HSIL or worse cervical lesions. The PANArray HPV assay alone was more sensitive than the ThinPrep alone for detecting HSIL or worse cervical lesions, however, co-testing enhanced the sensitivity. Co-testing is more useful for screening HSIL or worse lesions than use of either the ThinPrep or PANArray HPV genotyping alone.