Objectives.-To determine the performance of in-cell HPV E6, E7 mRNA quantification (HPV OncoTect) for the detection of high-grade cervical intraepithelial neoplasia in women younger than 30 years.Design.-We analyzed 3133 cytology specimens from a screening population of women aged 19-75 years investigate HPV OncoTect as a triage/secondary screening test for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) cytology in women younger than 30 years. Test results were compared to histology in 246 cases.Results.-The sensitivity of E6, E7 mRNA was 89% for CIN 2+ and 100% for CIN 3+ lesions in women 30 years and older. In women younger than 30 years, the sensitivity of E6, E7 mRNA for CIN 2+ lesions was 88% for CIN 2+ and 92% for CIN 3+ lesions. Abnormal cytology ($ASCUS) exhibited a sensitivity of 89% for CIN 2+ and 100% for CIN 3+ in women 30 years and older and 96% sensitivity for CIN 2+ and 93% sensitivity for CIN 3+ in women younger than 30. The specificity of E6, E7 mRNA was .80% for CIN 2+ and CIN 3+ in both groups of women compared to a specificity of abnormal cytology of ,10% for CIN 2+ and CIN 3+ in both groups.Conclusions.-HPV OncoTect demonstrates a performance that would be effective for ASCUS/LSIL triage in women including those younger than 30 years.(Arch Pathol Lab Med. 2012;136:956-960; doi: 10.5858/ arpa.2011-0180-OA) E ffective cervical cancer screening programs like those implemented in the United States have reduced the incidence and the mortality of cervical cancer.1 Current cervical cancer screening recommendations include the use of more sensitive human papilloma virus (HPV) assays as an adjunct to cervical cytology in women more than 30 years old in an attempt to identify those women at risk for high-grade cervical intraepithelial neoplasia (CIN 2+) or cervical cancer lesions. 2,3Women younger than 30 years old were shown to have more transient HPV infections, even by high-risk HPV types, making screening for CIN 2+ in this age group solely dependent on cytologic diagnosis. 4 Because approximately 15% of cervical cancer cases occur in women between 20 and 34 years of age, a need for improved cervical cancer screening exists in this age group. 5 To improve the performance of cervical cancer screening especially in women younger than 30 years, we investigated the use of a quantitative E6, E7 mRNA assay (HPV OncoTect, Incell DX, Menlo Park, California) that determines oncogene overexpression on a cell by cell basis using high throughput flow cytometry. 6,7 The E6 and E7 oncogenes drive cervical cell transformation leading to cancer. The expression of the HPV E6 gene leads to degradation of the tumor suppressor gene p53, and similarly, the HPV E7 gene associates with the tumor suppressor gene pRB.8,9 E7-pRB association results in the upregulation of an E2F-like transcription factor, allowing progression of the cell cycle through the G 1 /S phase. 10 The RB gene product represses expression of cyclin-dependent kinase inhibitor 2A (p16),...

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