Dayne Ashman

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

BackgroundPrevious 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.MethodsCases of ASC‐US/hrHPV+ that were tested using HC2, Cervista, or Aptima were retrieved, and the immediate histologic correlations were analyzed.ResultsOverall, 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.ConclusionThese 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.

HPV detection rates and histopathologic follow-up of patients with HSIL cytology in a large academic women’s hospital laboratory

High risk (hr) human papillomavirus (HPV) testing has been proposed as a possible replacement for Papanicolaou (Pap) cytology for cervical screening. The aim of the present study was to assess the hrHPV detection rates using 3 available Food and Drug Administration-approved HPV assays in patients with high-grade squamous intraepithelial lesion (HSIL) cytology results and to correlate the cervical screening test results with the immediate histopathologic findings. Cases with positive HSIL ThinPrep cytology findings, concurrent hrHPV testing results, and histopathologic follow-up results obtained within 6 months of the Pap/HPV co-testing were identified from July 2010 to April 2018. A total of 943 HSIL Pap tests were identified with adjunctive hrHPV co-testing, and hrHPV was detected in 883 (93.6%) of these 943 cases. Cervical intraepithelial neoplasia ≥2 (CIN2+) lesions were diagnosed in 71.5% of patients, including 3.2% with invasive squamous cell carcinoma (SCC). In all hrHPV testing platforms, the detection rate for CIN2+ was significantly greater for the patients with positive HPV testing (72.7%) than for those with negative HPV testing (53.4%). However, CIN2+ lesions, including 3 cases of SCC, were found in 24 of 45 women (53.4%) with HSIL Pap and negative HPV testing results. The risk of CIN2+ histopathologic findings was significantly greater for patients with hrHPV-positive HSIL results. However, a subset of patients with HPV-negative HSIL results were found to have CIN2+ lesions, including SCC. The long-term effects of primary HPV screening on cervical cancer incidence, stage, and prognosis remain uncertain.

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

BackgroundHigh‐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.MethodsHSIL 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.ResultsAptima 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).ConclusionsThis 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.