A mathematical analysis of HPV transmission dynamics and cervical cancer progression: The role of screening, prophylactic and therapeutic vaccination strategies

Abstract

Cervical cancer remains a significant global health threat in the 21st century, posing serious societal, public health, and economic challenges. Despite being largely preventable, it is the most common cancer among women worldwide, responsible for over 250,000 deaths annually. This study develops and analyzes a mathematical model that captures the transmission dynamics of Human Papillomavirus (HPV) infection and its progression to cervical cancer. The model incorporates key intervention strategies, including prophylactic vaccination, regular screening and treatment, as well as therapeutic vaccination. Mathematical analysis confirms that the model is both epidemiologically and mathematically well-posed. Using a Lyapunov function in conjunction with LaSalle’s Invariance Principle, we establish the global asymptotic stability of the disease-free equilibrium (DFE) when the effective reproduction number $R_e<1$, and the global stability of the endemic equilibrium when $R_e>1$. Bifurcation analysis reveals that the model exhibits a forward (degenerate) transcritical bifurcation at $R_e=1$, indicating that HPV infection becomes endemic and persists when $R_e$ exceeds unity. Conversely, when $R_e\le 1$, the force of infection diminishes, rendering the DFE globally stable. A sensitivity analysis was conducted to identify the most influential parameters governing HPV transmission and the progression to cervical cancer. Local sensitivity was assessed using the normalized forward finite difference method, while global sensitivity was evaluated using the Partial Rank Correlation Coefficient (PRCC) technique. Numerical simulations indicate that prophylactic HPV vaccination is the most impactful standalone intervention. However, a synergistic approach combining vaccination with regular screening, therapeutic vaccination, and treatment strategies such as immunotherapy integrated with induced pluripotent stem cells (iPSCs) and conventional chemotherapy offers a more rapid and substantial reduction in HPV infections. Such a multifaceted strategy is likely to accelerate the eradication of cervical cancer and significantly reduce the disease burden in the population.