Human papillomavirus driving cervical cancer: A mathematical model with persistent infection, cancer progression, and spontaneous remission
Human papillomavirus (HPV), a DNA virus, causes cervical cancer, which is 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 detection and establish a persistent infection. In this state, HPV inhibits apoptosis and allows genomic mutations to accumulate. Over many years, this can lead to dysplasia, genetic abnormalities, and eventually, invasive cancer with metastasis. While many individuals with persistent HPV infections experience spontaneous remission, a small proportion develop cervical cancer. In this study, we aim to understand the sharp contrast between cervical cancer and other solid tumors (cancers of epithelial tissues). We analyze a mathematical model for stochastic transitions between infection states, where the likelihood of persistent infection 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. Key parameters were estimated from data using the MCMC method. We conclude that major characteristics of cervical cancer arise from the strong age-dependence of viral genome incorporated into the epithelial tissue - shaped by the human sexual behavior - and from the very high rate of spontaneous remission.
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Japan Society for the Promotion of Science London Grant JP25KJ1929Japan Science and Technology Agency Moonshot Research and Development Program Grant JPMJMS2021Japan Society for the Promotion of Science FundingJapan Science and Technology Corporation FundingJapan Science and Technology Agency Grant JPMJSP2136