A modified Latent Class Model assessment of human papillomavirus-based screening tests for cervical lesions in women with atypical glandular cells: a Gynecologic Oncology Group study

Purpose: In the absence of gold standard diagnoses, we estimate age-specific false-positive and false-negative prediction rates of HPV-, cytology-, and histology-based tests for significant cervical lesions (SCL) in US women with AGC-NOS Pap smear diagnoses. Methods: Modified Latent Class Model (LCM) analyses, with prevalence of SCL modeled as a function of age, were applied to GOG-0171 study data (n = 122). The accuracies of several HPV-based tests, including Hybrid Capture II high-risk HPV (HC2 H-HPV); carbonic anhydrase IX (CA-IX); and invasive histological diagnosis, were compared. 1-PPV and 1-NPV were written as functions of sensitivity, specificity, and prevalence to obtain age-specific false-positive and false-negative rates. Results: The histology-based test was nearly perfect (sensitivity = 1.00, CI = 0.98—1.00; specificity = 0.99, CI = 0.96—1.00). Otherwise, HC2 H-HPV performed best (sensitivity = 1.00, CI = 1.00—1.00; specificity = 0.87, CI = 0.79—0.94). The false-positive detection rates (1-PPV) for HC2 H-HPV were high (>17 %) at each age, while those of the histological diagnoses were low (