TY - JOUR
T1 - Modeling the Time Dependence of the Association between Human Papillomavirus Infection and Cervical Cancer Precursor Lesions
AU - Schlecht, Nicolas F.
AU - Platt, Robert W.
AU - Negassa, Abdissa
AU - Duarte-Franco, Eliane
AU - Rohan, Thomas E.
AU - Ferenczy, Alex
AU - Villa, Luisa L.
AU - Franco, Eduardo L.
N1 - Funding Information:
This study was supported by an intramural grant from the Ludwig Institute for Cancer Research and by grants from the US National Cancer Institute (grant CA70269) and the Canadian Institutes of Health Research (grant MA13647). Dr. Nicolas F. Schlecht is the recipient of a predoctoral scholarship, Dr. Robert W. Platt is the recipient of a Scientist Award, and Dr. Eduardo L. Franco is the recipient of a Distinguished Scientist Award, all from the Canadian Institutes of Health Research.
PY - 2003/11/1
Y1 - 2003/11/1
N2 - The authors studied the time-dependent association between human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among women enrolled in a cohort study in Brazil (1993-2002), using repeated Papanicolaou cytologic examination and HPV testing by polymerase chain reaction. Through simulation with conceivable alternative cohort designs, they investigated different regression modeling approaches using time-varying covariates, time-varying hazard ratio functions, and repeated events to assess the effect of delay in lesion detection. Associations between HPV and early SIL were of high magnitude. The age-adjusted hazard ratios for the association between HPV at enrollment and low-grade SIL decreased gradually with time until 72 months for both oncogenic types of HPV (hazard ratio = 3.96, 95% confidence interval (CI): 2.5, 6.4) and nononcogenic types (hazard ratio = 2.37, 95% CI: 1.3, 4.3). The hazard ratio for incident high-grade SIL remained constant, ranging from 7.15 (95% CI: 2.0, 25.1) at 12 months to 6.26 (95% CI: 2.7, 14.5) at 72 months for oncogenic types of HPV. With oncogenic HPV as the time-dependent predictor variable, the hazard ratios for incident SIL and high-grade SIL events were 14.2 (95% CI: 8.7, 23.1) and 32.7 (95% CI: 8.4, 127.3), respectively. Investigators may underestimate the prognostic value of HPV detection using designs that rely on HPV ascertainment at a single time point. The waning in hazard ratios should be considered in the implementation of HPV testing-based screening programs.
AB - The authors studied the time-dependent association between human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among women enrolled in a cohort study in Brazil (1993-2002), using repeated Papanicolaou cytologic examination and HPV testing by polymerase chain reaction. Through simulation with conceivable alternative cohort designs, they investigated different regression modeling approaches using time-varying covariates, time-varying hazard ratio functions, and repeated events to assess the effect of delay in lesion detection. Associations between HPV and early SIL were of high magnitude. The age-adjusted hazard ratios for the association between HPV at enrollment and low-grade SIL decreased gradually with time until 72 months for both oncogenic types of HPV (hazard ratio = 3.96, 95% confidence interval (CI): 2.5, 6.4) and nononcogenic types (hazard ratio = 2.37, 95% CI: 1.3, 4.3). The hazard ratio for incident high-grade SIL remained constant, ranging from 7.15 (95% CI: 2.0, 25.1) at 12 months to 6.26 (95% CI: 2.7, 14.5) at 72 months for oncogenic types of HPV. With oncogenic HPV as the time-dependent predictor variable, the hazard ratios for incident SIL and high-grade SIL events were 14.2 (95% CI: 8.7, 23.1) and 32.7 (95% CI: 8.4, 127.3), respectively. Investigators may underestimate the prognostic value of HPV detection using designs that rely on HPV ascertainment at a single time point. The waning in hazard ratios should be considered in the implementation of HPV testing-based screening programs.
KW - Cervix neoplasms
KW - Longitudinal studies
KW - Papillomavirus, human
KW - Precancerous conditions
KW - Statistics
KW - Survival analysis
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U2 - 10.1093/aje/kwg235
DO - 10.1093/aje/kwg235
M3 - Article
C2 - 14585766
AN - SCOPUS:0142250422
SN - 0002-9262
VL - 158
SP - 878
EP - 886
JO - American Journal of Epidemiology
JF - American Journal of Epidemiology
IS - 9
ER -