title: A growth model of human papillomavirus type 16 designed from cellular automata and agent-based models.
abstract: OBJECTIVE
  This paper presents a conceptual model that is developed upon a characterization of human papillomavirus type 16 (HPV16) which is used to build a simulation prototype of the HPV16 growth process.
  
  
  METHODS
  The human papillomavirus type 16 is the principal virus detected in invasive lesions of cervical cancer, and associated with the greater persistence and prevalence in pre-malignant and malignant lesions. The probability of acquiring an infection with HPV16 is extremely high in sexually active individuals. However, an HPV16 infection can disappear after becoming a histological confirmed case. According to the characterization of HPV16 proposed in this paper, cells as compared to a society behaves as a complex system, i.e., cells behave in a cooperative manner, following a set of rules defined by local interactions among them. Such complex system is defined by combining a cellular automaton and agent-based models. In this way, the behavior of the HPV16 is simulated by allowing the cellular automaton to follow such parameterized behavior rules.
  
  
  RESULTS
  Both cross-sectional and prospective studies indicate that HPV16 infection persistence increase the risk of high-grade CIN, as observed in the results provided by the growth simulation model of HPV16. The average growth rate extrapolated over 52 weeks (12 months) and calculated by the model showed a 37.87% growth for CIN1, 35.53% for CIN2 and 16.92% for CIN3. Remarkably, these results are similar to the results obtained and reported by clinical studies. For example, the results obtained using the proposed model for CIN2 and the results obtained by Östör [36], have a differential of 0.53 percentage points while have a differential of 2.23 percentage points with the results obtained by Insinga et al. [51]. Also, for the CIN3, the results obtained using the proposed model, have a differential of 2.92 percentage points with the Insinga et al. [52], results.
  
  
  CONCLUSIONS
  Through the specification of parameterized behavior rules for HPV16 that are simulated under the combined technique of cellular automata and agent-based models, the HPV life cycle can be simulated allowing for observations at different stages. The proposed model then can be used as a support tool in the investigation of HPV16, in particular (as part of our future work) to develop drugs as agents in the control of the HPV16 disease.
authors.affiliation: Deparment of Engineering - Systems and Computing, Universidad Nacional, Avenida Carrera 30 45-03, Bogotá, Colombia.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Escobar Ospina
authors.forename: Jonatan Gómez
authors.initials: JG
authors.lastname: Perdomo
mesh_terms: D002453:Cell Cycle; D019295:Computational Biology; D003198:Computer Simulation; D003661:Decision Support Techniques; D018450:Disease Progression; D005260:Female; D052162:Human papillomavirus 16 / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010363:Pattern Recognition, Automated; D011379:Prognosis; D018570:Risk Assessment; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D014764:Viral Proteins