Aside from its causal association with cervical cancer, high-risk Human Papillomavirus (HPV) infections can lead to the development of oropharyngeal cancers. Over the last two decades, prevalence and incidence of high-risk HPV-positive oropharyngeal cancers in non-vaccinated populations has dramatically increased in affluent countries. Prophylactic HPV vaccines have already been shown to be highly efficacious in preventing persistent cervical infections and precancerous lesions associated with the most prevalent carcinogenic HPV types (HPV-16 and -18) and some related oncogenic HPV types.
We present here secondary endpoint results of a phase III/IV, community-randomized, controlled study (NCT 00534638) evaluating vaccine efficacy (VE) of the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18) against oncogenic HPV oropharyngeal infections in adolescent girls.
From 2007 to 2010, 80,272 adolescents aged 12-15 years from 33 randomized communities in Finland were invited to participate in the study. 22,444 girls and 11,968 boys were allocated to 3 arms (A, B, C) of 11 communities each. Vaccinated subjects received either AS04-HPV-16/18 or hepatitis B virus (HBV) vaccine at months 0-1-6.
Oropharyngeal samples were collected from girls born in 1994-95 after age 18.5 years and before age 19 years (5-6 years after vaccination). HPV DNA prevalence in the oropharyngeal samples was determined by SPF-10 line probe assay (LiPA) and Multiplex Type-specific PCR.
VE was defined as a relative reduction of oropharyngeal HPV prevalence among HPV-vaccinated pooled-arms A and B girls compared to all HPV non-vaccinated girls from arm C (control arm).
In arms A and B, 89.5% (8,235/9,203) of vaccinated girls and boys, and 89.6% (6,601/7,367) of vaccinated girls respectively, were blinded and received AS04-HPV-16/18. Other vaccinated participants in arms A and B (6,614) and all vaccinated subjects (10,724) in arm C received HBV vaccine.
| HPV type | Arm | N | n | VE (%) | 95%CI (LL – UL) | p-value |
|---|---|---|---|---|---|---|
| 16/18 | A & B | 3,192 | 9 | 82.4 | 47.3 – 94.1 | 0.002 |
| C | 1,679 | 27 | ||||
| 31/45 | A & B | 3,192 | 3 | 75.3 | 12.7 – 93.0 | 0.030 |
| C | 1,679 | 9 | ||||
| 31/33/45 | A & B | 3,192 | 9 | 69.9 | 29.6 – 87.1 | 0.006 |
| C | 1,679 | 16 | ||||
| CI: confidence interval; LL: lower limit; N: number of subjects; n: number of positive samples; UL: upper limit; VE (%): vaccine efficacy (1-Odd Ratio) | ||||||
AS04-HPV-16/18 shows evidence of high VE against oropharyngeal infections with vaccine HPV types (HPV-16/18) and other oncogenic HPV types (HPV-31/33/45) in adolescent girls vaccinated at the age of 12-15 years.
Funding: GlaxoSmithKline SA
* Authorship on behalf of the HPV-040 study group