Aside of the high protection against the most prevalent carcinogenic HPV types (16/18) provided by the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v), large efficacy trials have evidenced its protective effect against some non-vaccine oncogenic types. We present results from a post-hoc analysis on cross-protective vaccine effectiveness (VE) against non-vaccine HPV type cervical infections in adolescent girls from a large phase III/IV, community-randomized, controlled study (NCT00534638).
From 2007 to 2010, 22,444 girls and 11,968 boys from Finland born 1992-95 (aged 12-15 years) were allocated to 3 arms. Around ninety percent of vaccinated girls and boys in arm A (8,235/9,203) and of vaccinated girls in arm B (6,601/7,367) received AS04-HPV-16/18v. Other vaccinated subjects in arms A and B (6,614) and all in arm C (10,724) received hepatitis B virus vaccine.
HPV DNA prevalence of 14 high-risk and 11 low-risk types in cervical samples collected from female subjects when they were 18.5-19 years old was determined by SPF-10 line probe assay (LiPA) and Multiplex Type-specific PCR.
VE was calculated as a relative reduction of HPV prevalence by type in cervical samples among HPV-vaccinated girls from pooled arms A & B compared with non HPV-vaccinated girls from arm C (control arm). The analysis was performed on the total enrolled cohort (TEC), overall and by birth cohort (92-93 and 94-95), accounting for the differences in average age at vaccination (14-15 and 13-14 years old) and time to follow-up (3-4 and 5-6 years).
VE are presented for HPV-31, 33, 35 and 45 (no significant changes were shown for other types).
| HPV type | TEC | Arm | N | n | VE (%) | 95% CI (LL-UL) | p-value |
| 31 | Overall | A&B | 5,853 | 51 | 81.1 | 70.7–87.8 | <0.001 |
| C | 3,168 | 140 | |||||
| 92-93 | A&B | 3,075 | 26 | 79.3 | 62.1–88.7 | <0.001 | |
| C | 1,635 | 64 | |||||
| 94-95 | A&B | 2,778 | 25 | 80.3 | 68.1–87.8 | <0.001 | |
| C | 1,533 | 76 | |||||
| 33 | Overall | A&B | 5,853 | 121 | 47.4 | 29.2–60.9 | <0.001 |
| C | 3,168 | 124 | |||||
| 92-93 | A&B | 3,075 | 74 | 43.5 | 19.9–60.1 | 0.001 | |
| C | 1,635 | 69 | |||||
| 94-95 | A&B | 2,778 | 47 | 53.0 | 26.3–70.1 | 0.001 | |
| C | 1,533 | 55 | |||||
| 35 | Overall | A&B | 5,853 | 43 | 54.2 | 30.0–70.0 | <0.001 |
| C | 3,168 | 50 | |||||
| 92-93 | A&B | 3,075 | 27 | 43.0 | -1.6–68.1 | 0.057 | |
| C | 1,635 | 25 | |||||
| 94-95 | A&B | 2,778 | 16 | 65.1 | 27.2–83.3 | 0.005 | |
| C | 1,533 | 25 | |||||
| 45 | Overall | A&B | 5,853 | 24 | 74.6 | 55.5–85.5 | <0.001 |
| C | 3,168 | 52 | |||||
| 92-93 | A&B | 3,075 | 15 | 70.4 | 38.4–85.8 | 0.001 | |
| C | 1,635 | 26 | |||||
| 94-95 | A&B | 2,778 | 9 | 75.9 | 47.1–89.0 | <0.001 | |
| C | 1,533 | 26 | |||||
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CI: confidence interval; LL-UL: lower and upper limits; N: number of subjects; n: number of positive samples; TEC: total enrolled cohort; VE: vaccine effectiveness All analyses are exploratory. CI and p-value are based on Mantel-Haenszel adjusted for clustering and stratified by the historical HPV-16/18 seroprevalence used in the randomization. |
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Cross-protective effectiveness of AS04-HPV-16/18v against non-vaccine HPV type (31/33/35/45) cervical infections was observed in adolescent girls 3-6 years post vaccination. Protection appeared higher in younger birth cohorts.
Funding: GlaxoSmithKline Biologicals SA
*On behalf of the HPV-040 study group