Durability of Protection Afforded by Fewer Doses of the HPV16/18 Vaccine: The CVT Trial

Abstract

Background: Previously, we demonstrated similar human papillomavirus (HPV)16/18 vaccine efficacy estimates and stable HPV16/18 antibody levels four years postvaccination in a nonrandomized analysis of women who received a varying number of doses of the bivalent HPV16/18 vaccine. Here we extend data to seven years following initial vaccination.

Methods: We evaluated HPV16/18-vaccinated women who received one (n = 134), two (n 0/1 = 193, n 0/6 = 79), or three doses (n = 2043) to a median of 6.9 years postvaccination. Cervical HPV DNA was measured with the SPF10- DEIA-LiPA PCR system; HPV16/18-specific antibody levels were measured using enzyme-linked immunosorbent assays (n = 486). Infection and immunological measures were compared across vaccine dose groups. Prevalent HPV infection at year 7 was also compared with an unvaccinated control group (UCG). All statistical tests were two-sided.

Results: Among women in the three-dose, two-dose 0/6 , two-dose 0/1 , and one-dose groups, cumulative incident HPV16/18 infection rates (No. of events/No. of individuals) were 4.3% (88/2036, 95% confidence interval [CI] = 3.5% to 5.3%), 3.8% (3/78, 95% CI = 1.0% to 10.1%), 3.6% (7/192, 95% CI = 1.6% to 7.1%), and 1.5% (2/133, 95% CI = 0.3% to 4.9%; P = 1.00, .85, .17 comparing the two-dose 0/6 , two-dose 0/1 , and one-dose groups to the three-dose group, respectively). The prevalence of other carcinogenic and noncarcinogenic HPV types, excluding HPV16/18/31/33/45, were high and not statistically different among all dose groups, indicating that the low incidence of HPV16/18 in the one- and two-dose groups was not due to lack of exposure. At seven years, 100% of participants in all dose groups remained HPV16 and HPV18 seropositive. A non-statistically significant decrease in the geometric mean of the HPV16 antibody levels between years 4 and 7 was observed among women in the three-dose group: -10.8% (95% CI = -25.3% to 6.6%); two-dose (0/6 months) group: -17.3% (95% CI = -39.3% to 12.8%), two-dose (0/1 month) group: -6.9% (95% CI = -22.1% to 11.2%), and one-dose group: -5.5% (95% CI = -29.7% to 27.0%); results were similar for HPV18.

Conclusions: At an average of seven years of follow-up, we observed similar low rates of HPV16/18 infections and slight, if any, decreases in HPV16/18 antibody levels by dose group.

Figure 1.

Human papilloma virus (HPV) antibody levels over time by number of doses received. A) Anti-HPV16 and (B) anti-HPV18 antibody levels are presented in each of the four HPV vaccine groups. Added to previously published results (12) describing antibody levels by number of doses received throughout the first four years of follow-up (shown in solid lines), the new data describe antibody levels by number of doses received in years 4 and 7 of follow-up (shown in dashed lines). We note that antibody levels were measured using two batches of virus-like particles; because antigen characteristics vary by batch, direct comparisons can only be made within a batch. EU = enzyme-linked immunosorbent assay units; HPV = human papilloma virus.

Figure 2.

Absolute change in human papilloma virus (HPV) antibody levels by dose. Results for (A) HPV16 and (B) HPV18 are shown. The x-axis is the average level of serum antibody: (level at year 4 + level year 7)/2. The y-axis is the absolute change in antibody level between year 4 and year 7; each point represents an individual, and the color of that point indicates dose group. The solid line indicates a 2× change; the dashed line indicates a 1.5× change. ELISA = enzyme-linked immunosorbent assay.