Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Carter RL, Kang L, Darcy KM, Kauderer J, Liao S-Y, Rodgers WH, Walker JL, Lankes HA, S Dunn T, Stanbridge EJ |
Journal | Cancer Causes Control |
Volume | 23 |
Issue | 12 |
Pagination | 2013-21 |
Date Published | 2012 Dec |
ISSN | 1573-7225 |
Keywords | Adult, Aged, Cervical Intraepithelial Neoplasia, Cytodiagnosis, Early Detection of Cancer, Female, Humans, Mass Screening, Middle Aged, Papanicolaou Test, Papillomaviridae, Papillomavirus Infections, Sensitivity and Specificity, Vaginal Smears, Young Adult |
Abstract | 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 (<5 % at ages ≤60 and <17 % overall ages). False-negative prediction rates (1-NPV) for HC2 H-HPV were <0.11 % at each age and were uniformly lower than those of other tests, including the histology-based test (<0.25 %). CA-IX together with HC2 H-HPV did not improve performance. CONCLUSIONS: Women with negative HC2 H-HPV can safely forego invasive treatment (i.e., cone or LEEP biopsy, hysterectomy) in favor of observational follow-up. Additional biomarkers must be found for use in combination with HC2 H-HPV to reduce false-positive rates. This novel application of a modified LCM exemplifies methods for potential use in future cancer screening studies when gold standard diagnoses are not available. |
DOI | 10.1007/s10552-012-0081-0 |
Alternate Journal | Cancer Causes Control |
PubMed ID | 23073789 |
Grant List | CA 27469 / CA / NCI NIH HHS / United States CA 37517 / CA / NCI NIH HHS / United States |
Related Faculty:
William Rodgers, M.D., Ph.D.