Effects of Referral Bias on Estimates of Anal Intraepithelial Neoplasia Progression and Regression Rates in a 3-State Markov Model.
The study aim is to compare anal intraepithelial neoplasia (AIN) progression and regression rates in a cytology inception cohort to estimates based on the subcohort referred for ≥1 high-resolution anoscopies (HRAs).A cytology-based retrospective cohort was assembled including the anal cytology histories and invasive anal cancer (IAC) outcomes of all HIV-infected adults under care between 2001 and 2012. A 3-state Markov model (<HSIL↔HSIL→IAC) was estimated separately for all patients and for the subcohort undergoing ≥ 1 HRAs with biopsy. Cytology was adjusted for misclassification. State transition rates (per person-year) and covariate hazard ratios were estimated using the R package msm.Of 2804 eligible patients in the inception cohort, 629 (22%) were in the HRA subcohort and 2175 (78%) in the non-HRA subcohort. Patients in the HRA subcohort were more likely to have baseline CD4<350, viral load >400, and to have HSIL at baseline and thereafter. They also had more anal cytology examinations (median 6 vs 3) and longer follow-up (median 5.5 vs 3.6 years). State transition rates were overestimated in the HRA subcohort relative to inception cohort, but the degree of discordance varied by transition: for <HSIL to HSIL (0.44 vs 0.04); for HSIL to <HSIL (0.56 vs 0.17); and for HSIL to IAC (0.014 vs 0.011). Beneficial covariate effects on the <HSIL to HSIL transition were concordant (P < 0.05) for time-updated HIV viral load, CD4 count, and antiretroviral therapy. The observed effects of HRA-triage bias may be relevant to estimates of AIN state transitions from other cohorts subject to referral bias.
From the Department of Medicine, University of California San Diego, San Diego, California, United States of America (WCM, ERC, WA); and Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, United Kingdom (CJ).
William Christopher
WC
Mathews
Edward Rafael
ER
Cachay
Wollelaw
W
Agmas
Christopher
C
Jackson
D000328:Adult; D001005:Anus Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D001706:Biopsy; D002278:Carcinoma in Situ / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications; D006801:Humans; D015994:Incidence; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D015233:Models, Statistical; D009365:Neoplasm Regression, Spontaneous / Q000473:pathology; D012017:Referral and Consultation / Q000706:statistics & numerical data*; D012074:Remission Induction; D012189:Retrospective Studies; D015983:Selection Bias; D013997:Time Factors