A recent systematic review reports substantial heterogeneity in estimates of efficacy against high-grade cervical diseases irrespective of type for AS04-HPV-16/18 vaccine (AS04-HPV16/18) and HPV-6/11/16/18 vaccine (4vHPV).[1] In the current post-hoc analysis, we further explore the reported differences in efficacy.
Case counts of Cervical Intraepithelial Neoplasia of grade 2 and 3 (CIN2/3) cases were extracted from the FUTURE I/II study (NCT00092521/NCT00092534, Intention-to-Treat naive cohort) [2] and the PATRICIA study (NCT00122681, Total Vaccinated naive Cohort). Cases were assigned to the following categories based on HPV types found in the lesions:
- Lesions with at least one HPV vaccine type* and without any non-vaccine type**
- Co-infections: Lesions with at least one vaccine type* and at least one non-vaccine type**
- Lesions where no vaccine type* was detected (non-vaccine types** only or no high-risk HPV)
Efficacy against lesions with vaccine types, irrespective of type as well as cross-protective efficacies with both inclusion and exclusion of the co-infection cases are calculated using the case counts (n) and totals (N) as extracted.
|
Efficacy (95% CIs) [n vaccine/n control] |
Efficacy against lesions with at least one HPV vaccine type* including co-infections with a non-vaccine type** |
Efficacy irrespective of type |
Cross-protective efficacy including co-infections of a non-vaccine type** with an HPV vaccine type* |
Cross-protective efficacy excluding co-infections of a non-vaccine type** with an HPV vaccine type* |
|
|
PATRICIA N AS04-HPV16/18: 5466 N control: 5452 |
CIN2 |
98,9% (93.9 ; 100) [1/93] |
63,3% (50.4 ; 73.2) [60/163] |
47,5% (27.3 ; 62.3) [59/112] |
15,9% (-20.6 ; 41.6) [59/70] |
| CIN3 |
100% (81.8 ; 100) [0/22] |
92.1% (75.2 ; 98.4) [3/38] |
88.5% (62.4 ; 97.8) [3/26] |
81.3% (34.7 ; 96.5) [3/16] |
|
|
FUTURE I/II N 4vHPV: 4616 N control: 4680 |
CIN2 |
100% (91.9 ; 100) [0/48] |
42.8% (20.1 ; 59.4) [57/101] |
26.8% (-4.1 ; 48.9) [57/79] |
-9.0% (-61.6 ; 26.3) [57/53] |
| CIN3 |
100% (90.5 ; 100) [0/41] |
43.0% (12.9 ; 63.2) [36/64] |
13.1% (-39 ; 45.9) [36/42] |
-58.7% (-180.5 ; 8.5) [36/23] |
No head-to-head efficacy trials that compare different HPV vaccines have been conducted and methodological differences between trials cannot be excluded. However, our post-hoc analysis suggests that efficacy against CIN2 and CIN3 irrespective of type is largely influenced by lesions in which no vaccine type was found, resulting in different estimates for AS04-HPV16/18 and 4vHPV.
*Vaccine types in AS04-HPV16/18: HPV-16/18, 4vHPV: HPV-6/11/16/18
**Non-vaccine types in AS04-HPV16/18: HPV-31/33/35/39/45/51/52/56/58/59/66/68, 4vHPV: HPV-31/33/35/39/45/51/52/56/58/59.
[1] S.Di Mario, et al. J. Immunol. Res. (2015); 2015: 435141 (13p.)
[2] N.Munoz, et al. J. Natl. Cancer Inst. (2010); 102: 325-339.
Funding: GlaxoSmithKline SA
Conflicts of interest: MR, VB, NK and FS are employees of the GSK group of companies. MR, VB and FS also report shares from the GSK group of companies.