مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
The effect of the vaccines on the treatment of cancer and prevention of relapse in people with previous HPV infection
The effect of the vaccines on the treatment of cancer and prevention of relapse in people with previous HPV infection
Mohamad Hossein Ramezani,1,*Hafez Mozayyan Esfahani,2
1. Department of Microbiology, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani University, Isfahan, Iran. 2. Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
Introduction: Human papillomavirus (HPV) is the most prevalent sexually transmitted virus, with approximately 75–80% of sexually active women contracting HPV during their lifetime [1]. Persistent HPV infections can lead to various lesions, including cervical intraepithelial neoplasia (CIN) and cancers such as cervical, vulvar, vaginal, anal, and oropharyngeal cancers [2]. Prophylactic HPV vaccines, including Cervarix, Gardasil, Gardasil-9, and Cecolin, effectively prevent HPV infections by inducing long-term antibody responses but offer no therapeutic benefit for pre-existing infections [3, 4]. Therapeutic HPV vaccines aim to induce T-cell-mediated immune responses to clear established infections and prevent progression or relapse of HPV-associated diseases. This article explores the potential of therapeutic vaccines in treating HPV-related cancers and preventing relapse in previously infected individuals.
Methods: A comprehensive literature review was conducted using peer-reviewed articles from databases such as PubMed, focusing on studies published between 2017 and 2023. Keywords included "HPV therapeutic vaccines," "cervical cancer," "E6/E7 oncoproteins," and "T-cell immunity." Studies evaluating the efficacy of therapeutic vaccines targeting HPV oncoproteins E6, E7, and E2 in clinical and preclinical settings were included. Data on vaccine platforms (e.g., peptide-based, DNA-based, viral vector, and bacterial vector vaccines) and their immunological outcomes, such as cytotoxic T lymphocyte (CTL) induction and tumor regression, were analyzed. Clinical trials combining vaccines with immune checkpoint inhibitors (e.g., anti-PD-L1 antibodies) were also reviewed to assess synergistic effects.
Results: Therapeutic HPV vaccines target oncoproteins E6 and E7, which are constitutively expressed in HPV-associated malignancies, making them ideal for immunotherapy [5]. Various platforms, including peptide-based, DNA-based (e.g., VGX-3100), and bacterial vector vaccines (e.g., Lactobacillus-based), have been tested. Clinical trials, such as those with VGX-3100, demonstrated regression of CIN2/3 lesions and clearance of HPV 16/18 in some patients, with no detectable virus 18 months post-treatment [6]. Combination therapies with anti-PD-L1 antibodies enhanced immune responses and suppressed tumor growth [7]. However, no therapeutic vaccine has achieved irreversible cancer regression, partly due to immunosuppressive tumor microenvironments, including cancer-associated fibroblasts (CAFs) that exclude CD8+ T cells [8]. Preclinical models show high clearance rates, but human trials reveal lower efficacy, highlighting the need for improved vaccine immunogenicity and novel targets like E1 and E5 [8]. Adjuvants, such as Poly-ICLC, and combination with genetically engineered T-cell therapies (e.g., TCR-T targeting E7) show promise in enhancing vaccine efficacy [8]. Vaccines targeting E2 are effective for precancerous lesions but less so for advanced cancers.
Conclusion: Therapeutic HPV vaccines hold significant potential for treating HPV-associated cancers and preventing relapse by inducing robust T-cell responses against E6 and E7 oncoproteins. While current vaccines are safe and well-tolerated, their clinical efficacy is limited by immunosuppressive tumor microenvironments and suboptimal preclinical models. Advances in mRNA vaccine platforms, combination therapies with immune checkpoint inhibitors, and exploration of new antigenic targets like E1 and E5 could enhance outcomes. Future research should focus on overcoming immune evasion mechanisms and developing more representative preclinical models to translate promising preclinical results into effective clinical therapies.