[C13] Cancer Biology

[C13-01] Human papillomavirus driving cervical cancer: a mathematical model with persistent infection

*Rena Hayashi¹, Akane Hara², Yoh Iwasa¹ (1. Kyushu University (Japan), 2. Toyama University (Japan))

Keywords:

Human papillomavirus,Cervical cancer,Stochastic-process model

Human papillomavirus (HPV), a DNA virus, causes cervical cancer, the most common cancer among Japanese women in their forties. Upon infection, HPV temporarily proliferates but is usually eliminated by the immune system. However, if the virus enters the nuclei of epithelial cells, it can evade immune attacks and establish a persistent infection. By inhibiting the tumor suppressor genes p53 and Rb, HPV prevents apoptosis and allows genomic mutations to accumulate. Over many years, this can lead to dysplasia, various genetic abnormalities, and eventually, invasive cancer with metastasis. Interestingly, many individuals with persistent HPV infections experience spontaneous remission, with only a small proportion developing cervical cancer. In this study, we analyze a mathematical model for stochastic transitions between infection states, where the likelihood of persistence is proportional to the cumulative viral load, influenced by viral dynamics, immune effectors, and immune memory. We derive formulas for total cancer incidence, mean age at diagnosis, and age variance, and discuss the impact of immune responses on these outcomes. Finally, we compare the characteristics of cervical cancer with those of other epithelial cancers.