Immediate histologic correlation in women with atypical squamous cells of undetermined significance cytology and positive high-risk HPV: A retrospective review of 6000 cases in a large academic women's hospital.

Previous studies of the histologic correlation in women who have atypical squamous cells of undetermined significance cytology (ASC-US) and are positive for high-risk human papillomavirus (hrHPV+) have predominantly utilized the Hybrid Capture 2 (HC2) test, whereas the use of other US Food and Drug Administration (FDA)-approved methods is relatively limited. Cases of ASC-US/hrHPV+ that were tested using HC2, Cervista, or Aptima were retrieved, and the immediate histologic correlations were analyzed. Overall, 53.9% (n = 3238) of women with ASC-US/hrHPV+ had immediate histologic correlation. The detection rates for grade 1 cervical intraepithelial neoplasia (CIN1) were similar among the 3 methods (37.1%-41.8%), while the overall detection rates for grade 2 CIN or higher (CIN2+) were much lower (5.1%-9.0%). CIN2+ detection rates were similar among different age groups for HC2 testing, whereas for Cervista and Aptima testing, detection rates were highest in the youngest group (age <25 years) and decreased with age. Statistical analyses revealed that the CIN2+ detection rate was significantly higher in younger women who were tested with Cervista. These hrHPV testing methods revealed low CIN2+ detection rates in women with ASC-US/hrHPV+ but demonstrated different patterns when using age-stratified analyses. The high rate of CIN2+ detection in women aged <25 years by the Cervista and Aptima testing platforms, but not the HC2 platform, suggest that continual investigation of FDA-approved clinical hrHPV testing-especially large-scale, long-term, prospective studies-is needed to evaluate the best options for management of ASC-US/hrHPV+ in this age group.

Zhang H ，Pradhan D ，Wang T ，Ashman D ，Matsko J ，Zhao C ... -  《-》

Clinical performance of the aptima HPV assay in 4196 women with positive high-risk HPV and ASC-US cytology: A large women hospital experience.

Despite Aptima assay as the latest US Food Drug Administration (FDA)-approved high-risk human papillomavirus (hrHPV) test has been implemented as an adjunct in cervical cancer screening for years, histological follow-up data remain limited with respect to its performance in women with ASC-US Pap tests and positive hrHPV results. Cases with results of ASC-US cytology and positive hrHPV by Aptima assay during the period 06/ 2015-02/2017 were retrieved from archived pathology reports. Immediate histological follow-up results were analyzed within 6 months interval after cotesting. Among 4196 women with ASC-US Pap tests and positive hrHPV, 51.1% of them had the immediate histological follow-up within 6 months. With positive Aptima hrHPV as the adjunct, 46.5% (95%CI 46.2-46.8) of ASC-US women were found to have cervical intraepithelial neoplasia type 1 (CIN1); 8.8% (95%CI 8.1-9.5) women were detected CIN2+ lesion including eight adenocarcinoma in-situ (AIS)s. CIN2+ detection rates were highest in women under 25 (15.4%, n = 65), when comparison with different age cutoffs, younger age women had higher CIN2+ lesion detection rate than that in older group (P <.01). This is by far one of the largest retrospective studies to analyze the histological follow-up results of ASC-US women with positive hrHPV tested by Aptima hrHPV mRNA assay. The results indicated that younger women with ASC-US and positive hrHPV testing have highest risk of developing high grade CIN lesions as compared to the older women. Lastly, with positive HPV as the adjunct, 55.3% (1186/2145) of ASC-US women will result in the positive finding on histological follow-up.

Wang T ，Pradhan D ，Zhang H ，Matsko J ，Zhao C ... -  《-》

Presence of koilocytosis in low-grade smears of high-risk HPV-positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more.

The Netherlands converted to high-risk (hr)HPV-based screening in 2017. An increase in referral of hrHPV-positive women with low risk for cervical intraepithelial neoplasia grade 3 or more (CIN3+) is anticipated and reduction of unjustified referrals will have priority. The relevance of koilocytosis in relation to the underlying risk of high-grade CIN in a primary HPV screening setting is unclear. The aim was to investigate whether the risk for CIN3+ differs between hrHPV-positive atypical squamous cells of undetermined significance (ASC-US)/low-grade squamous intraepithelial lesion (LSIL) with or without koilocytosis. Retrospective cohort study, using data from the Dutch national pathology database (PALGA). The population was 1201 hrHPV-positive women with cytological diagnosis of ASC-US/LSIL. Reporting of koilocytosis was assessed as well as detection rates of CIN1 or less, CIN2 and CIN3+ for ASC-US/LSIL cytology stratified by presence or absence of koilocytosis. Crude and adjusted odds ratios were determined. Koilocytosis was present in 40.1% of ASC-US and 45.9% of LSIL cases. CIN3+ is significantly less often found when koilocytosis is present (7.8% for hrHPV-positive ASC-US with- vs 15.8% without koilocytosis). For hrHPV-positive LSIL this was 11.7% vs 20.2%. The crude and adjusted odds ratios for CIN3+ was 0.45 for hrHPV-positive ASC-US and 0.52 for hrHPV-positive LSIL. The presence of koilocytosis is a negative predictor of CIN3+. The risk of hrHPV-positive ASC-US with koilocytosis is in the same range as hrHPV-positive/cytology negative cases and in a setting of primary hrHPV screening these cases could be followed conservatively by repeat cytology. The results should be confirmed by the first data from the Dutch HPV-based screening programme.

Siebers AG ，van der Linden H ，Vedder JEM ，Bekkers RLM ，Melchers WLG ，Bulten J ... -  《-》

Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain.

Ibáñez R ，Moreno-Crespi J ，Sardà M ，Autonell J ，Fibla M ，Gutiérrez C ，Lloveras B ，Alejo M ，Català I ，Alameda F ，Casas M ，Bosch FX ，de Sanjosé S ... -  《BMC INFECTIOUS DISEASES》

Atypical squamous cells of undetermined significance cervical cytology in the Chinese population: Age-stratified reporting rates, high-risk HPV testing, and immediate histologic correlation results.

The US American Society of Colposcopy and Cervical Pathology guidelines for cervical cancer screening have been largely adopted worldwide. Pooled high-risk human papillomavirus (hrHPV) testing has been routinely used to risk-stratify women who have atypical squamous cells of undetermined significance (ASC-US) cytology. However, it has been reported that there are distinguished differences in the distribution of hrHPV genotypes between the Chinese and American populations. The objective of this study was to analyze the age-stratified reporting rates, hrHPV-positive rates, and genotyping by different cytology preparation methods and hrHPV testing assays, along with the immediate histopathologic correlation of ASC-US cytology, in the Chinese population. The ASC-US reporting rate of 1,597,136 Papanicolaou (Pap) tests was 4.2%, and the overall hrHPV-positive rate was 48.7% in the ASC-US cases. In total, 25,338 women with ASC-US Pap tests had immediate histologic follow-up, and the detection rate for cervical intraepithelial neoplasia 2 and higher lesions (CIN2+) was 7.1%, including 0.6% carcinomas. Among the women who underwent hrHPV testing, CIN2+ lesions were identified in 657 of 6154 (10.7%) who had hrHPV-positive results and in only 1.5% those who had hrHPV-negative results. Further genotyping analysis revealed that HPV types 16 and/or 18 were commonly identified genotypes among the Chinese women who had ASC-US cytology. This large-scale study demonstrated that the hrHPV-positive rate, the CIN2+ detection rate, and the distribution of hrHPV genotypes in Chinese women with ASC-US cytology were essentially consistent with those from the American population, further supporting that the current and newly released 2019 American Society of Colposcopy and Cervical Pathology guidelines should be applicable to the Chinese population.

Tao X ，Zhang H ，Wang L ，Pan Q ，Ji S ，Zhou X ，Zhao C ... -  《-》