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Development and Calibration of a Mathematical Model of Anal Carcinogenesis for High-Risk HIV-Infected Men.

ABSTRACT: OBJECTIVES:Men who have sex with men who are living with HIV are at highest risk for anal cancer. Our objective was to use empirical data to develop a comprehensive disease simulation model that reflects the most current understanding of anal carcinogenesis, which is uniquely positioned to evaluate future anal cancer screening strategies and provide insight on the unobservable course of the disease. SETTING:North America. METHODS:The individual-based simulation model was calibrated leveraging primary data from empirical studies, such as a longitudinal HIV-positive men who have sex with men cohort study [Human Immunodeficiency and Papilloma Virus Research Group (HIPVIRG); n = 247] and the North American AIDS Cohort Collaboration on Research and Design [(NA-ACCORD); n = 13,146]. We used the model to infer unobservable progression probabilities from high-grade precancer to invasive anal cancer by CD4 nadir and human papillomavirus (HPV) genotype. RESULTS:The calibrated model had good correspondence to data on genotype- and age-specific HPV prevalence; genotype frequency in precancer and cancer; and age- and nadir CD4-specific cancer incidence. The model-projected progression probabilities differed substantially by HPV genotype and nadir CD4 status. For example, among individuals with CD4 nadir <200, the median monthly progression probability from a high-grade lesion to invasive cancer was 0.054% (ie, 6.28% 10-year probability) and 0.004% (ie, 0.48% 10-year probability) for men with an HPV-16 infection versus without a detectable HPV infection, respectively. CONCLUSIONS:We synthesized existing evidence into a state-of-the-art anal cancer disease simulation model that will be used to quantify the tradeoffs of harms and benefits of alternative strategies, understand critical uncertainties, and inform national anal cancer prevention policy.

SUBMITTER: Burger EA

PROVIDER: S-EPMC6092220 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Development and Calibration of a Mathematical Model of Anal Carcinogenesis for High-Risk HIV-Infected Men.

Burger Emily A EA Dyer Michael A MA Sy Stephen S Palefsky Joel M JM de Pokomandy Alexandra A Coutlee François F Silverberg Michael J MJ Kim Jane J JJ

Journal of acquired immune deficiency syndromes (1999) 20180901 1

<h4>Objectives</h4>Men who have sex with men who are living with HIV are at highest risk for anal cancer. Our objective was to use empirical data to develop a comprehensive disease simulation model that reflects the most current understanding of anal carcinogenesis, which is uniquely positioned to evaluate future anal cancer screening strategies and provide insight on the unobservable course of the disease.<h4>Setting</h4>North America.<h4>Methods</h4>The individual-based simulation model was ca ...[more]

PMID: 29757775

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Project description:BackgroundThe progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines.ObjectiveThis study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons.DesignUsing the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer.SettingsThis is a population-based study.PatientsIncluded were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III.Main outcome measuresThe primary outcome measured was incident squamous cell carcinoma of the anus.ResultsStudy subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%-2.5%) and 5.7% (95% CI, 4.0%-8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04).LimitationsThe identification of some incident cancer episodes used surrogate measures.ConclusionsIn our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.

Dataset Information

Development and Calibration of a Mathematical Model of Anal Carcinogenesis for High-Risk HIV-Infected Men.

Publications

Development and Calibration of a Mathematical Model of Anal Carcinogenesis for High-Risk HIV-Infected Men.

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