Hope in the Long Road Toward the Development of a Therapeutic Human Papillomavirus Vaccine

Abstract

A pool of long synthetic peptides derived from HPV16 proteins induce objective partial or complete histologic regression of lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3).The intensity of T-cell response induced by the vaccine was correlated with clinical response. Clin Cancer Res; 22(10); 2317-9. Ó2016 AACR.See related article by van Poelgeest et al., p. 2342 In this issue of Clinical Cancer Research, van Poelgeest and colleagues report the clinical results of a therapeutic human papillomavirus (HPV) vaccine for the treatment of premalignant anogenital lesions (1). Currently, two prophylactic vaccines against oncogenic HPV16 and HPV18, the genotypes predominantly found in cancers, and a new vaccine directed against 9 HPV serotypes have demonstrated their efficacy in non-HPV-infected individuals. However, these vaccines failed to demonstrate any clinical activity in subjects already infected with HPV with 14 million new HPV infections each year in the world. In a subgroup of patients who do not spontaneously clear their infection, premalignant lesions will ultimately be followed by the development of invasive cancer of the cervix, anus, vagina, penis, and oropharynx. In addition, only a few countries have achieved vaccine coverage exceeding 50%. Therapeutic HPV vaccines (THV), therefore, correspond to a currently unmet medical need. van Poelgeest and colleagues report the ability of ISA 101 vaccine [13 HPV16 E6 and E7 synthetic long peptides mixed with the Montanide adjuvant] without additional treatment to induce objective partial or complete histologic regression of the lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3) with a follow-up of 12 months (1). Interestingly, 7 of 29 patients displayed complete response, which coincided with clearance of HPV16 likely to indicate complete cure. The only potential bias of this clinical trial was the absence of a control arm, but, as recalled by the authors, spontaneous regression of the lesions is observed in less than 1.5% of cases, a much lower rate than the clinical response observed after vaccination (>50%). This report therefore confirms the efficacy of ISA 101 to elicit durable complete regression in vulvar intraepithelial neoplasia (2). These results extend recent findings from a randomized control trial based on an HPV DNA vaccine, which induced regression of HPV16-or HPV18-positive CIN2/3 in 48.2% of cases compared with a spontaneous regression rate of 30% in the placebo arm (3).A different HPV DNA vaccine administered in 9 CIN3 patients also induced complete regression of lesions and viral clearance in 7 patients (4). A recombinant Modified Vaccinia Ankara (MVA) HPV16 E6 and E7 cDNA vaccine achieved cytologic clearance of CIN2/3 lesions and clearance of HPV16 virus in previously infected tissue in 7 of 10 patients (5).The first administration of THV was 1996 and, after many . Surprisingly, they did not observe a correlation be...

Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors

“…Since HPV infection is associated with 5%–7% of cancer (cervical cancer, oropharyngeal cancer, anal cancer, etc. ), various therapeutic HPV vaccines have been developed with encouraging results, especially in patients with preneoplastic lesions [4,5,6,7,8]. …”