Natural History of Anal Dysplasia in an HIV-Infected Clinical Care Cohort: Estimates Using Multi-State Markov Modeling

Abstract

Objectives(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.DesignA retrospective cytology-based inception screening cohort of HIV-infected adults was analyzed using a 3-state Markov model of clinical pathogenesis of anal neoplasia.MethodsLongitudinally 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.ConclusionsThe 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.

Human papillomavirus status, anal cytology and histopathological outcome in HIV‐positive patients

“…In accord with previously published papers CD4 + cell nadir and recent CD4 + cell count were not associated with higher dysplasia (Table ) . On the other hand, two recent studies showed a protective effect of ART against high risk AIN . Nevertheless, these incongruent findings highlight the importance of routine screening and diagnostic also for HIV‐positive patients who receive optimal therapy and have good immune cell status.…”

Anal Dysplasia Screening and Treatment in a Southern Human Immunodeficiency Virus Clinic

“…7–11 A nonstatistically significant trend was found for individuals with suppressed viral load on the single variable analysis (Table 3) to have a reduced odds of having HSIL (OR, 0.54; 95% CI, 0.26–1.11; P = 0.094), which would have been consistent with prior data. 12 Additionally, cigarette smoking was found to have a nonstatistically significant trend toward increased odds of developing HSIL in both the single variable and multivariable logistic regression analysis of the data (Tables 3 and 4), and this was consistent with prior literature. 7 …”

Histopathologic and Cytologic Follow-Up in High Risk Male Patients with Unsatisfactory Anal Cytology

“…The role of HPV testing in anal cytology remains to be elucidated and was not analyzed in this study. There is a high likelihood of regression of HGSIL at two-year follow-up with only about 1-2% progressing to anal cancer [15]. Patients on antiretroviral therapy, who had low HIV viral load, and a CD4 count greater than or equal to 350/mm 3 were not as likely to progress from lower grade lesions to higher grade lesions [15].…”

“…There is a high likelihood of regression of HGSIL at two-year follow-up with only about 1-2% progressing to anal cancer [15]. Patients on antiretroviral therapy, who had low HIV viral load, and a CD4 count greater than or equal to 350/mm 3 were not as likely to progress from lower grade lesions to higher grade lesions [15]. The role of viral load, medication status, and CD4 count was not assessed, and there is one limitation in this study.…”