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

Burger, Emily A., PhD*,†; Dyer, Michael A., MD; Sy, Stephen, MS*; Palefsky, Joel M., MD§; de Pokomandy, Alexandra, MD, MSc║,¶; Coutlee, François, MD#; Silverberg, Michael J., PhD, MPH**; Kim, Jane J., PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1, 2018 - Volume 79 - Issue 1 - p 10–19
doi: 10.1097/QAI.0000000000001727

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.

*Department of Health Policy and Management, Center for Health Decision Science, Harvard T.H. Chan School of Public Health, Boston, MA;

Department of Health Management and Health Economics, University of Oslo, Oslo, Norway;

Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA;

§Department of Medicine, University of California, San Francisco, CA;

Chronic Viral Illness Service, McGill University Health Centre, Montreal, Quebec, Canada;

Department of Family Medicine, McGill University, Montreal, Quebec, Canada;

#Université de Montréal, Département de Microbiologie et Infectiologie, Montreal, Quebec, Canada; and

**Division of Research, Kaiser Permanente, Oakland, CA.

Correspondence to: Emily A. Burger, PhD, Center for Health Decision Science, Harvard T.H. Chan School of Public Health, 718 Huntington Avenue, 2nd Floor, Boston, MA 02117 (e-mail:

Supported by the National Cancer Institute (R01CA160744, R01CA165937), the Fonds de la Recherche en Santé du Québec Réseau FRQS-SIDA MI and by the Research Council of Norway (Grant number 238042).

Presented at Society of Medical Decision Making; October 20, 2014, and International Papillomavirus Conference; February 28–March 4, 2017; Cape Town, South Africa.

The authors have no funding or conflicts of interest to disclose.

E.A.B., J.M.P. and J.J.K. contributed to the conception and design of the study; all authors contributed to the analysis and interpretation of the data. E.A.B. drafted the manuscript and all authors contributed to revising the manuscript for critically important content. All authors have approved the final article.

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Received January 08, 2018

Accepted April 27, 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.