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.
OBJECTIVE
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.
GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY, USA. rcarter@buffalo.edu
Randy L
RL
Carter
Le
L
Kang
Kathleen M
KM
Darcy
James
J
Kauderer
Shu-Yuan
SY
Liao
William H
WH
Rodgers
Joan L
JL
Walker
Heather A
HA
Lankes
S Terence
ST
Dunn
Eric J
EJ
Stanbridge
D000328:Adult; D000368:Aged; D003581:Cytodiagnosis; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D065006:Papanicolaou Test; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D012680:Sensitivity and Specificity; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology*