Abstract
High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches.
Highlights
Cervical cancer is the third most common cancer worldwide [1,2]
This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic human papillomavirus (HPV) vaccination, and highlights selected promising preclinical studies
DNA-based vaccines have been investigated as an attractive therapeutic approach against malignancies since they are safe, can be produced at high purity, provide stable expression of the encoded antigen [86], and may have adjuvant functions, as plasmid DNA itself harbors unmethylated CpG motifs, which can be recognized by Toll-like receptor (TLR)-9 [87,88]
Summary
Cervical cancer is the third most common cancer worldwide [1,2]. Annually, almost half a million women are diagnosed with cervical cancer [3]. Over 80% of all cervical cancer cases occur in developing countries [4]. Cervical cancer and its precursors are caused by various types of the human papillomavirus (HPV) [5]. Two prophylactic HPV vaccines are currently available. Cancers can be caused by the spectrum of non-16/18 HR types that are not covered by the currently existing vaccines (around 30% of cases in cervical cancer [11]). HPV are being found in anogenital lesions, especially in human immunodeficiency virus (HIV) infected subjects [12]. The available preventative vaccines have no therapeutic effects, i.e., they are not effective once HPV infection is established. Existing therapeutic modalities for HPV-induced premalignant lesions are surgical, and can lead to impaired function of the affected tissue (such as causing premature births in pregnancies following cervical conizations). HPV vaccines are an attractive option [14,15]
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