Current state in the development of candidate therapeutic HPV vaccines

ABSTRACT

The identification of human papillomavirus (HPV) as an etiological factor for HPV-associated malignancies creates the opportunity to control these cancers through vaccination. Currently, available preventive HPV vaccines have not yet demonstrated strong evidences for therapeutic effects against established HPV infections and lesions. Furthermore, HPV infections remain extremely common. Thus, there is urgent need for therapeutic vaccines to treat existing HPV infections and HPV-associated diseases. Therapeutic vaccines differ from preventive vaccines in that they are aimed at generating cell-mediated immunity rather than neutralizing antibodies. The HPV-encoded early proteins, especially oncoproteins E6 and E7, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated malignancies and precancerous lesions, playing crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we review strategies to enhance vaccine efficacy and the latest clinical trials on therapeutic HPV vaccines.

KEYWORDS:

• HPV
• human papillomavirus
• immunotherapy
• therapeutic vaccines
• cervical cancer
• clinical trials
• HPV E6
• HPV E7
• adjuvant
• combinatorial approach

Acknowledgements

The authors thank Emily Robitschek for her input and critical review of the manuscript. This review is not intended to be an encyclopedic one, and the authors apologize to those not cited.

Financial and competing interests disclosure

This work was funded by the United States National Institutes of Health (NIH) Cervical Cancer Specialized Program of Research Excellence (SPORE) (P50 CA098252) and R01 grant (CA114425-01). T-C Wu is a founder of and has an equity ownership interest in Papivax LLC. Also, he own Papivax Biotech Inc. stock options and is a member of Papivax Biotech Inc.’s Scientific Advisory Board. Additionally, T-C Wu and C-F Hung are entitled to royalties on an invention described in this article. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.