Invader human papillomavirus (HPV) type 16 and 18 assays as adjuncts to HPV screening of cervical papanicolaou smears with atypical squamous cells of undetermined significance.

Abstract

High-risk (HR) human papillomavirus (HPV) testing is standard practice for triaging women who have Papanicolaou (Pap) smears with atypical squamous cells of undetermined significance (ASC-US), however, only 5% to 17% of these women have underlying cervical intraepithelial neoplasia 2 (CIN-2)/CIN-3. Recent reports have demonstrated that the presence of either HPV type 16 (HPV-16) or HPV-18 confers an elevated risk for CIN-2/CIN-3. The current study was designed to determine the prevalence of HPV-16 and HPV-18 in ASC-US Pap smears and to determine whether further typing would enhance the risk stratification of patients for CIN-2/CIN-3. One hundred seventy-eight Pap smears with ASC-US were screened retrospectively for HR HPV by using the proprietary Invader screening assay followed by typing for HPV-16 and HPV-18 by using Invader type-specific probes on 100 of the samples. Clinical follow-up results were correlated with HPV types. Fifty-one percent of the ASC-US samples were positive for HR HPV, the majority of which (70%) harbored non-HPV-16/HPV-18 HR HPV types; 27% were associated with HPV-16, whereas only 3% contained HPV-18. The screening assay indicated that 46% of women who had Pap smears with ASC-US were in need of further HPV-16/HPV-18 typing. Testing for HPV-16 stratified women with ASC-US into 3 groups: 1) 14% of women were positive for HPV-16 and had a high risk (54%) of CIN-2/CIN-3 on follow-up biopsy, 2) 35% of women were positive for non-HPV-16 HPV types and had an intermediate risk (9%), and 3) 51% of women were negative for HPV and had a negligible risk for CIN-2/CIN-3. The combined application of a proprietary screening assay and a type-specific HPV-16 assay demonstrated global potential for the development of tailored management protocols for women who have Pap smears with ASC-US.