# Quantifying Genetic and Environmental Factors Accounting for Multistage Progression of Precancerous Lesions and Oral Cancer: Applications to Risk-Guided Prevention

## TL;DR

This paper introduces a new model that combines genetic and environmental factors to better predict and prevent oral cancer, especially in high-risk groups.

## Contribution

The study introduces a multistate disease progression model integrating genetic and environmental factors for precision prevention of oral cancer.

## Key findings

- Integrating genetic and environmental factors improves risk stratification for oral cancer.
- Tailored screening and health education reduce oral cancer incidence, especially in high-risk groups.
- Frequent screening is more effective for individuals with higher risk profiles.

## Abstract

Oral squamous cell carcinoma (OSCC) develops through a multistage process driven by both environmental exposures and genetic predisposition. However, current screening programs often consider only environmental exposures, missing the added value of genetic susceptibility. This study proposes an innovative approach by integrating genetic and environmental data into a multistate disease progression model to estimate individual oral cancer risk. Using computer simulations, the study demonstrates that tailored screening strategies can significantly reduce oral cancer incidence, particularly among high-risk groups. These findings offer a new framework for precision prevention and could help guide the development of more effective screening strategies in public health.

Background: Oral squamous cell carcinoma (OSCC) is a multifactorial and multistage disease influenced by both genetic susceptibility and environmental risk factors. However, conventional oral cancer preventions are often based on environmental exposures but do not allow for genetic susceptibility and both factors contributing to multistage progressions. This study developed a comprehensive multistate risk model combining both types of factors. Methods: Using data from literature, the researchers built a multistate progression model and calculated transition risks to simulate outcomes in a high-risk population, similar to those eligible for oral cancer screening in Taiwan. Results: The findings showed that OSCC risk varied dramatically across the population, ranging from 362 to over 24,000 cases per 100,000, depending on risk level. The integration of genetic and environmental risk factors into a multistate disease model allows for more accurate risk stratifications of precancerous and invasive OSCC. Frequent screening is more effective, notably in high-risk individuals. Incorporating a health education program provided an additional 2 to 6% reduction in incidence, particularly benefiting higher-risk groups. Simulation findings indicate that tailored screening strategies, particularly when combined with health education interventions, can significantly improve the effectiveness of oral cancer prevention. Conclusions: Quantifying the effects of genetic susceptibility and environmental factors on multistate natural history of precancerous lesions and oral cancer provides a valuable framework for developing the risk-guided policies for oral cancer prevention.