HPV Testing With 16, 18, and 45 Genotyping Stratifies Cancer Risk for Women With Normal Cytology.

To determine the BD Onclarity human papillomavirus (HPV) assay performance and risk values for cervical intraepithelial neoplasia grade 2 (CIN2) or higher and cervical intraepithelial neoplasia grade 3 (CIN3) or higher during Papanicolaou/HPV cotesting in a negative for intraepithelial lesions or malignancies (NILM) population. In total, 22,383 of the 33,858 enrolled women were 30 years or older with NILM cytology. HPV+ and a subset of HPV- patients (3,219/33,858 combined; 9.5%) were referred to colposcopy/biopsy. Overall, 7.9% of women were Onclarity positive; HPV 16 had the highest prevalence (1.5%). Verification bias-adjusted (VBA) CIN2 or higher and CIN3 or higher prevalences were 0.9% and 0.3%, respectively. Onclarity had VBA CIN2 or higher (44.1%) and CIN3 or higher (69.5%) sensitivities, as well as CIN2 or higher (92.4%) and CIN3 or higher (92.3%) specificities-all similar to Hybrid Capture 2. HPV 16, 18, 45, and the other 11 genotypes had CIN3 or higher risks of 6.9%, 2.6%, 1.1%, and 2.2%, respectively. Onclarity is clinically validated for cotesting in NILM women. Genotyping actionably stratifies women at greater CIN3 or higher risk.

Stoler MH ，Wright TC ，Parvu V ，Yanson K ，Eckert K ，Kodsi S ，Cooper C ... -  《-》

Stratified risk of high-grade cervical disease using onclarity HPV extended genotyping in women, ≥25 years of age, with NILM cytology.

Increasing evidence suggests that extended human papillomavirus (HPV) genotyping (beyond 16/18) is effective for risk stratification in women with normal cytology. This report provides extended genotyping results, using the BD Onclarity HPV Assay, for individual genotypes HPV16, 18, 31, 45, 51, and 52 ̶ and three pooled genotype results for HPV33/58, 35/39/68, and 56/59/66. 27,037 women with normal cytology, ≥25 years, were enrolled into the Onclarity HPV trial during routine screening. Women positive for any HPV genotype were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with cervical intraepithelial neoplasia, grade 2 or worse (≥CIN2) or ≥CIN3, were calculated based on extended genotyping results. HPV 16 and 31 carried the highest risk for ≥CIN2 (11.6% and 12.1%, respectively) and ≥CIN3 (8.1% and 7.5%, respectively); these genotypes were the most prevalent in both ≥CIN2 (29.6% and 19.3%, respectively) and ≥CIN3 (43.7% and 22.5%, respectively). Of the other 12 genotypes, HPV 18, 33/58, and 52 comprised an intermediate risk band (≥CIN2 risk range: 4.9-6.8%; ≥CIN3 risk range: 3.9-5.0%). Genotypes 45, 51, 35/39/68, and 56/59/66 constituted the lowest risk band for both disease grades (≥CIN2 value risk range: 1.7-3.0%; ≥CIN3 value risk range: 1.2-3.6%). Extended genotyping stratifies risk for ≥CIN2/3 in the ≥25 year-old, normal cytology population. While baseline HPV 16/31 values exceeded the risk threshold for colposcopy referral, the management of women with normal cytology who were positive for the intermediate- or lower-risk genotypes may evolve based on refined risk estimates as well as clinical factors.

Stoler MH ，Wright TC Jr ，Parvu V ，Yanson K ，Cooper CK ，Andrews J ... -  《-》

[Evaluation of CIN2+ /CIN3+ risk of different HPV subtypes infection combined with abnormal cytology status].

Luo HX ，Du H ，Liu ZH ，Zhang LJ ，Wang C ，Wu RF ... -  《-》

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 ... -  《-》

Primary HPV testing verification: A retrospective ad-hoc analysis of screening algorithms on women doubly tested for cytology and HPV.

To evaluate human papillomavirus (HPV) testing as a primary screening tool, we retrospectively analyzed data comparing (1) HPV testing to the algorithms of the ATHENA Study: (2) cytology alone, (3) cytology with ASCUS triage in women 25-29 and (4) cotesting ≥ 30 or (5) cotesting ≥ 25. We retrospectively analyzed data from women tested with both cytology and HPV testing from 2010 to 2013. Cumulative risk (CR) for CIN3+ was calculated. Crude and verification bias adjusted (VBA) sensitivity, specificity, predictive values, likelihood ratios, colposcopy rate, and screening test numbers were compared. About 15,173 women (25-95, 7.1% <30) had both HPV and cytological testing. Nearly 1,184 (8.4%) had biopsies. About 19.4% had positive cytology, 14.5% had positive HPV. HPV testing unassociated with ASCUS was requested in 40% of women <30, versus 84% ≥30, with similar HPV16/18 genotyping results (68% vs. 70%). 84 CIN3+ were detected with the following 3-year cumulative risk (CR) (95% confidence interval): HPV+/ASCUS+, 46% (32-66%), HPV+/NILM 30% (15-58%), HPV-/ASCUS+ 12% (6-23%), and HPV-/NILM 0.8% (0.2-3.6%). HPV had higher specificity 57% (54-60%) than cotesting ≥30 52% (49-55%). HPV sensitivity 78% (69-87%), positive 12.3% (9.8-15.3%), negative 97 (96-98%) predictive values, positive 1.8 (1.6-2.1) and negative likelihood ratios 0.6 (0.5-0.6), were not significantly different. Cotesting increased colposcopy rate and doubled testing per CIN3+ diagnosed. While HPV-/NILM cotesting results are associated with low CIN3+ risk, HPV testing had similar screening performance to cotesting and to cytology alone. Additionally, HPV testing and cytology incur false negatives in nonoverlapping subsets of patients. Diagn. Cytopathol. 2017;45:580-586. © 2017 Wiley Periodicals, Inc.

Tracht J ，Wrenn A ，Eltoum IE 《-》