Bivalent HPV vaccination has shown strong protection against persisting HPV16 and 18 infections, but less against incident infections. This study aimed to assess the effects of bivalent vaccine on the viral load (VL) of HPV16 and 18 in an observational cohort study. In addition, VL assays were developed for HPV6, 11, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66 to assess possible vaccine cross-protective effects.
Samples were obtained annually from an observational cohort study with vaccinated (3V) and non-vaccinated girls (0V). Up to eight samples were available per study participant. Genotyping occurred via the SPF10-DEIA-LiPA25 platform. Type-specific (TS) qPCR assays were developed for HPV6, 11, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66. Sensitivities of TS assays were in line with SPF10 or better. Participants were included in analysis if TS HPV DNA negative at baseline. Group differences in TS VL of 3V and 0V participants were assessed by Mann-Whitney testing. Persistent infection VL measurements were pooled per year of duration for each type and median was plotted with 95% CI. HPV TS incidence and persistence rates (IR, PR) were calculated by generalized estimating equation to assess protective vaccine effects.
In total 555 women (50.1% 3V; 49.9% 0V) with TS incident and 451 (49.9% 3V; 50.1% 0V) with TS persistent HPV infections were included in VL analysis. For incident infections, vaccine type VL values were lower in the 3V group (HPV16 p=0.04, HPV18 p<0.01). (Borderline) lower VLs were found in 3V for HPV6 (p=0.08), 51 (p=0.07) and 59 (p=0.01). No significant effects on VL were found for other HPV types. Persistent infections showed similar kinetics over time for both groups for any HPV type.
Reduced VL was associated with reduced IR of HPV16 and reduced PR for HPV16 and HPV18 among 3V, implying protection. Despite effects on VL for HPV6 and 51, no changes in IR or PR were observed for 3V, suggesting no cross-protective vaccine effect. Interestingly, for HPV59 a reduced VL seemed associated with an increased PR among 3V. For HPV31, 33, 35 and 45 possible cross-protective effects were observed, as reduced IR were found in 3V for these types, as well as a reduced PR for HPV31. However, no link with VL was identified.
Reduced VL for both HPV16 and HPV18 was found in vaccine recipients, possibly explaining lower occurrences of persistent HPV16 and 18 infections among 3V. Cross-protective effects of the vaccine were not associated with VL measurements, possibly due to the limited size of the dataset. Kinetics of VL in persistent infections did not differ between 3V and 0V for any HPV type, but number of infections was limited per HPV type.