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

Abstract

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.

High‐grade squamous intraepithelial lesion cervicovaginal paps with negative high‐risk HPV testing, a prospective study with histological follow‐up

“…Another study by Li et al 12 using the Aptima hrHPV test of 951 patients with HSIL paps showed 46 (4.8%) negative for hrHPV. Of these cases, 15 of 35 (42.9%) had HSIL (CIN2/3) or worse on tissue follow‐up, with one invasive SCC.…”

Prevalence of cervical precancers or cancers in women with ASC-H/HSIL cytology according to Aptima HPV (AHPV) assay-detected HPV genotypes and age

“…A study conducted in Shanghai, a region with a similar economic status to our study population, showed that 71.5% of patients with HSIL cytology were diagnosed with CIN2+ lesions, including 3.2% with invasive squamous cell carcinoma (SCC) 23 . Additionally, they conducted another study revealing a CIN2+ rate of 76.8% in hrHPV mRNA-positive cases 15 . Similarly, our study observed a CIN2+ rate of 66.1% in hrHPV mRNA-positive cases.…”

“…While most cervical cytology abnormalities are not severe and will not develop into cancer or its precursors, high-grade cervical cytology abnormalities, most of which were positive for hrHPV, have a higher risk of precancerous and cancerous cervical lesions 14 , and these patients often undergo immediate treatment 6 . However, different genotypes of hrHPV carry different risks of developing high-grade lesions 15 . In our previous studies, we demonstrated the benefit of risk-stratifying patients with NILM and ASC-US cytology based on hrHPV genotype for optimizing patient management 16 , 17 .…”