Safaeian Mahboobeh, Sampson Joshua N, Pan Yuanji, Porras Carolina, Kemp Troy J, Herrero Rolando, Quint Wim, van Doorn Leen Jan, Schussler John, Lowy Douglas R, Schiller John, Schiffman Mark T, Rodriguez Ana Cecilia, Gail Mitchell H, Hildesheim Allan, Gonzalez Paula, Pinto Ligia A, Kreimer Aimée R
Roche Molecular Diagnostics, Pleasanton, CA; National Cancer Institute, National Institutes of Health, Bethesda, MD; HPV Immunology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD; Agencia Costarricense de Investigaciones Biomédicas (ACIB), formerly Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica; Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France; DDL, Diagnostic Laboratory, Rijswijk, the Netherlands; Information Management Systems, Silver Spring, MD.
J Natl Cancer Inst. 2018 Feb 1;110(2):205-12. doi: 10.1093/jnci/djx158.
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.
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.
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.
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.
此前，我们在一项对接受不同剂量二价人乳头瘤病毒（HPV）16/18疫苗的女性进行的非随机分析中表明，接种疫苗四年后HPV16/18疫苗效力评估结果相似，且HPV16/18抗体水平稳定。在此，我们将数据扩展至初次接种疫苗后的七年。
我们评估了接种HPV16/18疫苗的女性，她们分别接受了一剂（n = 134）、两剂（n0/1 = 193，n0/6 = 79）或三剂（n = 2043）疫苗，随访至接种疫苗后中位数为6.9年。使用SPF10-DEIA-LiPA PCR系统检测宫颈HPV DNA；使用酶联免疫吸附测定法检测HPV16/18特异性抗体水平（n = 486）。比较各疫苗剂量组的感染和免疫指标。还将7年时的HPV现患感染情况与未接种疫苗的对照组（UCG）进行比较。所有统计检验均为双侧检验。
在三剂组、两剂0/6组、两剂0/1组和一剂组的女性中，HPV16/18累积感染发病率（事件数/个体数）分别为4.3%（88/2036，95%置信区间[CI] = 3.5%至5.3%）、3.8%（3/78，95%CI = 1.0%至10.1%）、3.6%（7/192，95%CI = 1.6%至7.1%）和1.5%（2/133，95%CI = 0.3%至4.9%；将两剂0/6组、两剂0/1组和一剂组分别与三剂组比较，P值分别为1.00、0.85、0.17）。除HPV16/18/31/33/45外，其他致癌和非致癌HPV类型的现患率较高，且在所有剂量组之间无统计学差异，这表明一剂组和两剂组中HPV16/18低发病率并非由于暴露不足所致。在7年时，所有剂量组的100%参与者HPV16和HPV18血清学仍为阳性。在三剂组女性中观察到4至7年间HPV16抗体水平几何平均数有非统计学显著下降：-10.8%（95%CI = -25.3%至6.6%）；两剂（0/6个月）组：-17.3%（95%CI = -39.3%至12.8%），两剂（0/1个月）组：-6.9%（95%CI = -22.1%至11.2%），一剂组：-5.5%（95%CI = -29.7%至27.0%）；HPV18的结果相似。
在平均7年的随访中，我们观察到各剂量组HPV16/18感染率均较低，且HPV16/18抗体水平即使有下降也很轻微。
