Cervical cancer, caused by high-risk Human papillomavirus (HPV), arises from precancerous epithelial changes. Current treatments, including chemotherapy, are often limited by severe side effects and incomplete eradication of cancer cells. To address these challenges, we develop a mathematical model to analyze the progression of HPV-induced cervical cancer and evaluate a new treatment strategy that combines immunotherapy based on induced pluripotent stem cells (iPSC) with chemotherapy. The model incorporates key biological processes such as the differentiation of iPSC into effector cells, the proliferation of effector cells, and interactions with cancerous and infected cells. The stability analysis of the model reveals two equilibrium states: disease-free and endemic, with the basic reproduction number <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12190_2025_2476_Article_IEq1.gif" Format="GIF" Height="16" Rendition="HTML" Resolution="72" Type="Linedraw" Width="22" /> </InlineMediaObject> <EquationSource Format="TEX">\(\mathcal{R}_0\)</EquationSource> </InlineEquation> playing a crucial role in the system’s dynamics. Sensitivity analysis is performed to identify the impact of significant system parameters on the dynamics of the proposed system using both the Partial Rank Correlation Coefficient (PRCC) and the Latin Hypercube Sampling (LHS) method. Furthermore, we have invoked a combined treatment approach aimed at minimizing infected and cancerous cell proliferation while reducing the side effects of iPSC-chemotherapy drugs, and we have numerically analyzed various treatment strategies in a time frame of <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12190_2025_2476_Article_IEq2.gif" Format="GIF" Height="14" Rendition="HTML" Resolution="72" Type="Linedraw" Width="54" /> </InlineMediaObject> <EquationSource Format="TEX">\(0-450\)</EquationSource> </InlineEquation> days. The results show that the most effective strategy, iPSC-chemotherapy (T3), significantly reduces infected and cancerous cells, achieving near-complete elimination in  500 days. In addition, a cost-effectiveness analysis using the Incremental Cost-Effectiveness Ratio (ICER) method has confirmed that strategy  T3  is significantly more efficient with 98.14% efficacy than standalone therapies. These findings provide valuable insights for optimizing HPV-related cancer treatments and may inform future clinical strategies aimed at reducing treatment side effects while improving patient outcomes.

A mathematical framework investigating the impact of Chemo-iPSC therapy for the dynamics of cervical cancer

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发表日期：

2025年4月17日

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Amit Kumar Bag,
Salil Ghosh,
Amar Nath Chatterjee,
Priti Kumar Roy

摘要

Cervical cancer, caused by high-risk Human papillomavirus (HPV), arises from precancerous epithelial changes. Current treatments, including chemotherapy, are often limited by severe side effects and incomplete eradication of cancer cells. To address these challenges, we develop a mathematical model to analyze the progression of HPV-induced cervical cancer and evaluate a new treatment strategy that combines immunotherapy based on induced pluripotent stem cells (iPSC) with chemotherapy. The model incorporates key biological processes such as the differentiation of iPSC into effector cells, the proliferation of effector cells, and interactions with cancerous and infected cells. The stability analysis of the model reveals two equilibrium states: disease-free and endemic, with the basic reproduction number \(\mathcal{R}_0\) playing a crucial role in the system’s dynamics. Sensitivity analysis is performed to identify the impact of significant system parameters on the dynamics of the proposed system using both the Partial Rank Correlation Coefficient (PRCC) and the Latin Hypercube Sampling (LHS) method. Furthermore, we have invoked a combined treatment approach aimed at minimizing infected and cancerous cell proliferation while reducing the side effects of iPSC-chemotherapy drugs, and we have numerically analyzed various treatment strategies in a time frame of \(0-450\) days. The results show that the most effective strategy, iPSC-chemotherapy (T₃), significantly reduces infected and cancerous cells, achieving near-complete elimination in 500 days. In addition, a cost-effectiveness analysis using the Incremental Cost-Effectiveness Ratio (ICER) method has confirmed that strategy T₃ is significantly more efficient with 98.14% efficacy than standalone therapies. These findings provide valuable insights for optimizing HPV-related cancer treatments and may inform future clinical strategies aimed at reducing treatment side effects while improving patient outcomes.