Clinical validation of the PCR-reverse dot blot human papillomavirus genotyping test in cervical lesions from Chinese women in the Fujian province: a hospital-based population study.

To determine the clinical significance of the polymerase chain reaction (PCR)-reverse dot blot (RDB) human papillomavirus (HPV) genotyping assay in cervical cancer screening. A total of 10,442 women attending the Fujian Provincial Maternity and Children's Health Hospital were evaluated using the liquid-based cytology (thinprep cytologic test [TCT]) and the PCR-RDB HPV test. Women with HPV infection and/or abnormal cytology were referred for colposcopy and biopsy. For HPV DNA sequencing, 120 specimens were randomly selected. Pathological diagnosis was used as the gold standard. Using the PCR-RDB HPV test, overall HPV prevalence was 20.57% (2,148/10,442) and that of high-risk (HR)-HPV infection was 18.68% (1,951/10,442). There was 99.2% concordance between HPV PCR-RDB testing and sequencing. In this studied population, the most common HR-HPV types were HPV-16, -52, -58, -18, -53, -33, and -51, rank from high to low. HPV-16, -18, -58, -59, and -33 were the top 5 prevalent genotypes in cervical cancer but HPV-16, -18, -59, -45, and -33 were the top 5 highest risk factors for cancer (odds ratio [OR]=34.964, 7.278, 6.728, 6.101, and 3.658; all p<0.05, respectively). Among 10,442 cases, 1,278 had abnormal cytology results, of which, the HR-HPV positivity rate was 83.02% (1,061/1,278). To screen for cervical cancer by PCR-RDB HPV testing, when using CIN2+, CIN3+, and cancer as observed endpoints, the sensitivity was 90.43%, 92.61%, and 94.78% and the negative predictive value (NPV) was 99.06%, 99.42%, and 99.78%, respectively. PCR-RDB HPV and TCT co-testing achieved the highest sensitivity and NPV. For cervical cancer screening, the PCR-RDB HPV test can provide a reliable and sensitive clinical reference.

Sun P ，Song Y ，Ruan G ，Mao X ，Kang Y ，Dong B ，Lin F ... -  《-》

PCR-reverse dot blot human papillomavirus genotyping as a primary screening test for cervical cancer in a hospital-based cohort.

To evaluate the polymerase chain reaction (PCR)-reverse-dot-blot (RDB) human papillomavirus (HPV) genotyping test as a feasible assay for the cervical cancer primary screening. In a hospital-based cohort, a total of 21,568 women were voluntarily enrolled from March 2009 to November 2016 for evaluating the 3 current cervical cancer screening strategies: co-test, cytology primary and high-risk HPV (HR-HPV) primary by using PCR-RDB HPV genotyping and liquid-based cytology (thinprep cytologic test [TCT]). Women with HR-HPV infection and/or abnormal cytology were referred for colposcopy, and the biopsy or conization was performed according to the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines. Overall, 18.20% (3,935/21,568) of the women were detected as HR-HPV-positive, 5.04% (1,088/21,568) were diagnosed with cervical intraepithelial neoplasia 2 or higher (CIN2+), and 3.43% (739/21,568) with CIN3+. The cumulative incidence rates for CIN2+/CIN3+ in patients with HPV-16/18-positive were 48.28%/37.20%, while they were 0.86%/0.38%, 0.30%/0.15% and 0.18%/0.09% in cytology-negative, HR-HPV-negative and co-test-negative population, respectively. Using CIN2+ and CIN3+ as the observed endpoints, the sensitivity and negative predictive value (NPV) of HR-HPV genotyping as a primary screening tool were 90.99%/99.49% and 91.57%/99.80%. Moreover, using HR-HPV genotyping primary screening could detect the same more CIN2+/CIN3+ cases in baseline-detection as co-testing (990/700 vs. 991/701) and far more than cytology primary screening (903/656, p<0.05). It also achieved the lowest misdiagnosis rate (8.01%/5.02%). Although HPV genotyping primary screening required an increased number of colposcopies (2.75/3.89 per CIN2+/CIN3+ case), it yielded an acceptable rate. The PCR-RDB HPV genotyping test is a cost-effective and beneficial cervical cancer primary screening for hospital-based opportunistic screening.

Kang Y ，Sun P ，Mao X ，Dong B ，Ruan G ，Chen L ... -  《-》

Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear.

Monsonego J ，Pollini G ，Evrard MJ ，Sednaoui P ，Monfort L ，Quinzat D ，Dachez R ，Syrjänen K ... -  《INTERNATIONAL JOURNAL OF STD & AIDS》

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

The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice. 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. 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. The results of the current study support the use of the cervical cancer screening guidelines in China.

Pan QJ ，Hu SY ，Guo HQ ，Zhang WH ，Zhang X ，Chen W ，Cao J ，Jiang Y ，Zhao FH ，Qiao YL ... -  《-》

Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study.

The ATHENA study was designed to assess the performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping compared with liquid-based cytology for cervical cancer screening in a large US population aged 21 years and older. We did a subanalysis of this population to compare the screening performance of the cobas HPV test versus liquid-based cytology in women aged 25 years and older, and assess management strategies for HPV-positive women. Women aged 25 years or older who were attending routine cervical screening were enrolled from 61 clinical centres in 23 US states. Cervical specimens were obtained for liquid-based cytology and HPV DNA testing with two first-generation assays (Amplicor HPV test and Linear Array HPV genotyping test) and the second-generation cobas HPV test (with individual HPV16 and HPV18 detection). Colposcopy and diagnostic biopsies were done on women with atypical squamous cells of undetermined significance (ASC-US) or worse cytology, those who tested positive with either first-generation HPV test, and a random sample of women who tested negative for HPV and cytology. All women not selected for colposcopy received their results and exited the study. Participants and colposcopists were masked to cytology and HPV test results until the colposcopy visit was completed. The primary endpoint for this substudy was histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3) or worse. This study is registered with ClinicalTrials.gov, number NCT00709891; the study is in the follow-up phase, which is due to be completed in December, 2012. From May 27, 2008, to Aug 27, 2009, 47,208 women were enrolled, of whom 41,955 met our eligibility criteria. Valid cobas HPV and liquid-based cytology test results were available for 40,901 women (97%), who were included in this analysis. Of these, 4275 women (10%) tested cobas HPV positive and 2617 (6%) had abnormal cytology. 431 women were diagnosed with CIN2 or worse and 274 with CIN3 or worse. In women who had colposcopy, the cobas HPV test was more sensitive than liquid-based cytology for detection of CIN3 or worse (252/274 [92·0%, 95% CI 88·1-94·6] vs 146/274 [53·3%, 95% CI 47·4-59·1]; difference 38·7%, 95% CI 31·9-45·5; p<0·0001). Addition of liquid-based cytology to HPV testing increased sensitivity for CIN3 or worse to 96·7% (265/274, 95% CI 93·9-98·3), but increased the number of screen positives by 35·2% (5783/40,901 vs 4275/40,901) compared with HPV testing alone. As a triage test to identify CIN3 or worse in HPV-positive women, detection of HPV16, HPV18, or both alone was equivalent to detection of ASC-US or worse alone in terms of sensitivity (150/252 [59·5%] vs 133/252 [52·8%]; p=0·11) and positive predictive value (PPV) (150/966 [15·5%] vs 133/940 [14·1%]; p=0·20). Among HPV-positive women, detection of HPV16, HPV18, or both or low-grade squamous intraepithelial lesion or worse cytology had better sensitivity (182/252 [72·2%]; p<0·0001) and similar PPV (182/1314 [13·9%]; p=0·70) for detection of CIN3 or worse than ASC-US or worse cytology alone. Furthermore, detection of HPV16, HPV18, or both or high-grade squamous intraepithelial lesion or worse cytology had higher sensitivity (165/252 [65·5%]; p=0·0011) and PPV (165/1013 [16·3%]; p=0·031) for detection of CIN3 or worse than ASC-US or worse cytology alone. HPV testing with separate HPV16 and HPV18 detection could provide an alternative, more sensitive, and efficient strategy for cervical cancer screening than do methods based solely on cytology. Roche Molecular Systems.

Castle PE ，Stoler MH ，Wright TC Jr ，Sharma A ，Wright TL ，Behrens CM ... -  《-》