Human papillomavirus therapeutic vaccines: targeting viral antigens as immunotherapy for precancerous disease and cancer

Abstract

Infections with oncogenic HPV types have the potential to lead to the induction of several types of cancer, notably cervical, vulvar, anal, and head and neck cancer. While prophylactic vaccines are currently available and show high efficacy against the establishment of HPV infection, low rates of initiation and lower rates of completion of the vaccination regimen, as well as the lack of an opportunity to be vaccinated prior to infection, has lead to the development of a patient population for whom no immune-based therapy for infection is available. In the current review the authors examine clinical approaches to HPV-targeted immune therapies, the bulk of which target the regulatory proteins E6 and E7 that are constitutively expressed in HPV-associated cancer cells. Early studies demonstrate a correlation between induction of T-cell responses and clearance of HPV-associated precancerous lesions. The clinical data corroborates these findings and highlight the importance of Th1 skewing. Improvements in our understanding of tumor immunology and development of more potent Th1-directed vaccine platforms make it feasible to foresee a HPV therapeutic vaccine in the coming years.

Keywords::

• cervical cancer
• CIN2/3
• HPV immunotherapy
• therapeutic vaccine

Financial & competing interests disclosure

The authors thank ongoing grant and contract support from the NIH, PATH-MVI and DOD on vaccine development programs. MP Morrow, J Yan and NY Sardesai are employees of Inovio Pharmaceuticals, Inc. and receive salary and benefits and own stock/stock options in the company. The authors have no other relevant affiliations or financial involvement with any organi-zation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.