Changes over time in papanicolaou cytology test and HPV test in a large women's academic center laboratory.

INTRODUCTION: In the past 2 decades, cervical cancer screening guidelines in the United States have undergone numerous revisions with recent greater emphasis on primary high-risk human papillomavirus (hrHPV) testing. MATERIALS AND METHODS: We examine the trends of Papanicolaou test and hrHPV testing at our large academic center across 4 years (2006, 2011, 2016, and 2021) over a 15-year period. The number of ThinPrep Papanicolaou and hrHPV tests, as well as the triggers for HPV testing, were retrospectively analyzed. RESULTS: A total of 308,355 Papanicolaou tests and 117,477 hrHPV tests were reported across the 4 years. The number of Papanicolaou tests performed decreased nearly 3-fold over the study period, with only 43,230 Papanicolaou tests performed in 2021. The HPV test to Papanicolaou test ratio increased: 17% of Papanicolaou tests had an associated HPV test in 2006, whereas 72% of Papanicolaou tests ordered in 2021 had a companion hrHPV. The use of co-testing also increased. Overall, 73% were co-tests and 27% were reflexively ordered in the 4 one-year time periods. Co-tests constituted only 46% of HPV tests in 2006, but this increased to 93% in 2021. The percentage of positive hrHPV results decreased; in 2006, 18.3% of cases were positive, dropping to 8.6% in 2021 due to the marked increase in co-testing. Stratifying by diagnostic category, hrHPV results have remained relatively constant. CONCLUSION: With the numerous recent revisions of cervical screening guidelines, screening strategies at our institution reflected these changes in clinical practice. Papanicolaou and HPV co-testing became the most common screening method for women 30 to 65 years of age in our cohort.

Aptima HPV messenger RNA testing and histopathologic follow-up in women with HSIL cytology: A study emphasizing additional review of HPV-negative cases.

BACKGROUND: High-risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration-approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow-up study reported to date of hrHPV mRNA cotesting and histopathologic follow-up results for women with high-grade squamous intraepithelial lesion (HSIL) cytology results. METHODS: HSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow-up results within 6 months of screening. RESULTS: Aptima hrHPV mRNA-positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow-up in 538 of 701 hrHPV mRNA-positive cases (76.8%) and in 15 of 36 hrHPV mRNA-negative cases (41.7%). Additional reviews of the hrHPV mRNA-negative HSIL cases showed variable interpretations, and confirmatory blinded-review interpretations of HSIL or atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P < .01). CONCLUSIONS: This large routine-clinical-practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high-grade cervical dysplasia and cervical cancers. The blinded-review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV-negative HSIL cases.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

BACKGROUND: 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. METHODS: Cases of ASC-US/hrHPV+ that were tested using HC2, Cervista, or Aptima were retrieved, and the immediate histologic correlations were analyzed. RESULTS: 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. CONCLUSION: 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.

Immediate histopathologic follow-up of cervista and aptima high-risk HPV assays in women with LSIL cytology.

BACKGROUND: Recent guidelines recommended the optional deferral of colposcopy for postmenopausal women with low-grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap) test results and negative human papillomavirus (HPV) testing. The objective of the current study was to assess the histopathologic follow-up of Cervista and Aptima high-risk HPV (hrHPV) testing in patients with LSIL cytology. METHODS: Women with LSIL Pap test results and Cervista or Aptima hrHPV testing results were retrospectively identified from June 2013 through July 2017. Histological follow-up results within 6 months after LSIL Pap tests were analyzed. RESULTS: A total of 1731 and 1906 cases of LSIL Pap tests, respectively, were tested on Cervista and Aptima platforms. Among the 2119 cases with histopathologic follow-up, cervical intraepithelial neoplasia of types 2/3 (CIN2/3) was diagnosed in 184 women (8.9%) and the detection rate was significantly higher in women with positive HPV testing compared with those with a negative result on both assays. Both methods demonstrated comparable performance for detecting CIN2/3 lesions. However, in women aged ≥50 years, the specificity for the detection of CIN2/3 lesions by the Aptima assay was statistically significantly higher than that of the Cervista test (48.7% vs 23.1%; P<.01), although there were no significant differences in the sensitivity, positive predictive value, and negative predictive value between these 2 assays in this age group. CONCLUSIONS: The Aptima assay was found to be statistically significantly more specific than the Cervista test for detecting CIN2/3 lesions among women aged ≥50 years. These findings not only further support the recommendations by the American Society for Colposcopy and Cervical Pathology that hrHPV triage is an acceptable option for postmenopausal women with LSIL cytology, but also provide additional evidence that HPV RNA testing may be more useful in clinical risk stratification due to its specificity in the postmenopausal population. Cancer Cytopathol 2018. © 2018 American Cancer Society.