Emerging Therapeutic Strategies for Lung Cancer: The Role of Immunotherapy and HPV-Targeted Cancer Vaccines

Background/Objectives: Lung cancer remains the leading cause of cancer-related deaths globally, with non-small-cell lung cancer (NSCLC) accounting for most cases. Although advances in targeted therapies and immunotherapy have improved outcomes, long-term survival remains limited. This review aims to explore current immunotherapeutic strategies, the evolving role of therapeutic cancer vaccines, and the emerging potential of human papillomavirus-targeted interventions in lung cancer, particularly among non-smoker populations. Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and Web of Science databases to identify relevant articles published between 2015 and 2024. Studies focusing on immune checkpoint inhibitors, vaccine platforms, HPV-associated lung cancer, tumor microenvironment modulation, and novel delivery systems such as bacterial ghosts were included. Relevant clinical trials and preclinical studies were critically evaluated and synthesized. Results: Immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4 have demonstrated clinical efficacy in NSCLC, yet their effectiveness is often limited by resistance mechanisms and lack of robust predictive biomarkers. Cancer vaccines, including peptide-based, mRNA, DNA, dendritic cell, and bacterial ghost platforms are emerging as complementary strategies to enhance antitumor immunity. Moreover, accumulating evidence suggests a potential association between high-risk HPV infection and lung cancer development, supporting the rationale for HPV-targeted vaccine strategies. Conclusions: Immunotherapy and therapeutic vaccination hold significant promise in reshaping lung cancer treatment. Advancements in vaccine design, delivery platforms like bacterial ghosts, and better understanding of HPV's role in lung oncogenesis could support more effective, personalized immunotherapeutic approaches in the future.