title: Natural history of anal dysplasia in an HIV-infected clinical care cohort: estimates using multi-state Markov modeling.
abstract: OBJECTIVE
  (1) To model the natural history of anal neoplasia in HIV-infected patients using a 3-state Markov model of anal cancer pathogenesis, adjusting for cytology misclassification; and (2) to estimate the effects of selected time-varying covariates on transition probabilities.
  
  
  METHODS
  A retrospective cytology-based inception screening cohort of HIV-infected adults was analyzed using a 3-state Markov model of clinical pathogenesis of anal neoplasia.
  
  
  METHODS
  Longitudinally ascertained cytology categories were adjusted for misclassification using estimates of cytology accuracy derived from the study cohort. Time-varying covariate effects were estimated as hazard ratios.
  
  
  RESULTS
  (1) There was a moderate to high probability of regression of the high grade squamous intraepithelial lesion (HSIL) state (27-62%) at 2 years after initial cytology screening; (2) the probability of developing invasive anal cancer (IAC) during the first 2 years after a baseline HSIL cytology is low (1.9-2.8%); (3) infrared coagulation (IRC) ablation of HSIL lesions is associated with a 2.2-4.2 fold increased probability of regression to <HSIL; and (4) antiretroviral therapy, suppressed HIV plasma viral load, and CD4 ≥350/mm3 are each associated with reduced probability of progression from <HSIL to HSIL.
  
  
  CONCLUSIONS
  The finding of moderate to high rates of regression of the HSIL state accompanied by low rates of progression to IAC should inform both screening and precursor treatment guideline development. There appears to be a consistent and robust beneficial effect of antiretroviral therapy, suppressed viral load, and higher CD4 on the transition from the <HSIL state to the HSIL state.
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Mathews
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Wollelaw
authors.initials: W
authors.lastname: Agmas
authors.affiliation: Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Cachay
authors.affiliation: Department of Surgery, University of California San Diego, San Diego, California, United States of America.
authors.forename: Bard C
authors.initials: BC
authors.lastname: Cosman
authors.affiliation: Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Jackson
mesh_terms: D000328:Adult; D001005:Anus Neoplasms / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000453:epidemiology / Q000473:pathology / Q000628:therapy; D015497:HIV-1; D006801:Humans; D008297:Male; D008390:Markov Chains; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies
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