Moving forward with human papillomavirus immunotherapies

Abstract

Persistent human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and causes a significant number of vulvar, penile, anal and oropharyngeal cancers. The development of highly effective HPV therapeutic vaccines is a reasonable goal given the recent advances in basic and applied immunology. A number of vaccine strategies designed to induce systemic T cell responses have been tested in clinical trials against high grade cervical or vulvar high grade neoplasia and cancers, but with limited success. In line with the emerging trend to focus more on the epithelial context of HPV infection and premalignant disease, it might be advantageous to develop vaccination strategies that promote trafficking of HPV-specific T cells into lesions and overcome the local immunosuppressive environment. The development of more biologically relevant animal models would improve the preclinical evaluation of therapeutic vaccine candidates. Finally, persistent infection and low grade lesions may prove to be easier targets for therapeutic vaccines, and these vaccines would likely be commercially viable in high income countries and valuable components in screen and treat programs in low resource settings.

Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial

“…To be able to prevent cervical cancer in women aged less than 45 years the quadrivalent HPV vaccine was developed [33]. Recently, the therapeutic role of the HPV vaccine has been claimed in some studies [16,20,21]. In the present study, the impact of prophylactic quadrivalent HPV vaccine in the treatment of women with cervical intraepithelial neoplasia (CIN 1-3) was investigated.…”

“…Recent studies support the therapeutic role of the HPV vaccine [16,20,21]. It has been seen that presurgery HPV vaccination in women with HPV-related diseases significantly reduces the incidence of CIN 2-3 [16,22].…”

Human papillomavirus in cervical cancer and oropharyngeal cancer: One cause, two diseases

“…Despite their efficacy in preventing incident infection and disease, the vaccines do not influence clearance of prevalent HPV‐16/HPV‐18 infections and/or CIN . However, therapeutic vaccines designed to induce regression of existing HPV‐associated lesions are in development …”

“…81 However, therapeutic vaccines designed to induce regression of existing HPV-associated lesions are in development. 87 Biologically active compounds have demonstrated antiviral potential and warrant further investigation in human trials. For example, carrageenan, a seaweed extract and gelling agent in sexual lubricant, prevents HPV infection in cellular and mouse models.…”

Adenovirus vector‐based prime‐boost vaccination via heterologous routes induces cervicovaginal CD8+ T cell responses against HPV16 oncoproteins

“…Few preclinical studies have evaluated Ivag delivery of a vaccine for treatment of HPV‐induced neoplasia. Ongoing clinical trials for therapeutic treatment of CIN are introducing the use of topical toll‐like receptor (TLR) agonists such as Imiquimod to subvert the immune suppressive environment, promote immunogenic cell death and recruit HPV‐specific T cells . To date, impressive clinical response has been observed in a large clinical trial involving multiple rounds of intralesional injection of a Modified Vaccinia Ankara vector expressing bovine papillomavirus E2 protein .…”