Modeling the Time Dependence of the Association between Human Papillomavirus Infection and Cervical Cancer Precursor Lesions

Nicolas F. Schlecht, Robert W. Platt, Abdissa Negassa, Eliane Duarte-Franco, Thomas E. Rohan, Alex Ferenczy, Luisa L. Villa, Eduardo L. Franco

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)878-886
Number of pages9
JournalAmerican Journal of Epidemiology
Volume158
Issue number9
DOIs
StatePublished - Nov 1 2003

Fingerprint

Papillomavirus Infections
Uterine Cervical Neoplasms
Confidence Intervals
Brazil
Squamous Intraepithelial Lesions of the Cervix
Cohort Studies
Research Personnel
Polymerase Chain Reaction

Keywords

  • Cervix neoplasms
  • Longitudinal studies
  • Papillomavirus, human
  • Precancerous conditions
  • Statistics
  • Survival analysis

ASJC Scopus subject areas

  • Epidemiology

Cite this

Modeling the Time Dependence of the Association between Human Papillomavirus Infection and Cervical Cancer Precursor Lesions. / Schlecht, Nicolas F.; Platt, Robert W.; Negassa, Abdissa; Duarte-Franco, Eliane; Rohan, Thomas E.; Ferenczy, Alex; Villa, Luisa L.; Franco, Eduardo L.

In: American Journal of Epidemiology, Vol. 158, No. 9, 01.11.2003, p. 878-886.

Research output: Contribution to journalArticle

Schlecht, Nicolas F. ; Platt, Robert W. ; Negassa, Abdissa ; Duarte-Franco, Eliane ; Rohan, Thomas E. ; Ferenczy, Alex ; Villa, Luisa L. ; Franco, Eduardo L. / Modeling the Time Dependence of the Association between Human Papillomavirus Infection and Cervical Cancer Precursor Lesions. In: American Journal of Epidemiology. 2003 ; Vol. 158, No. 9. pp. 878-886.
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