Wheeler Cosette M, Adcock Rachael, Hunt William C, Robertson Michael, Torrez-Martinez Norah E, McDonald Ruth, Merchasin Emily, Jenison Steven, Saslow Debbie, Joste Nancy E, Castle Philip E, Kim Jane J, Cuzick Jack
Center for HPV Prevention, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131, United States.
Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, United States.
J Natl Cancer Inst. 2025 May 1;117(5):924-933. doi: 10.1093/jnci/djae327.
Various studies have reported on the impact of human papillomavirus (HPV) vaccines. Here we present the largest population-based investigation of genotype-specific distributions over the decade following implementation of the quadrivalent HPV vaccine (HPV-6/11/16/18) in the United States.
Liquid-based cervical cytology samples from individuals aged 15-30 years undergoing cervical screening throughout New Mexico were tested by broad-spectrum HPV genotyping. Weighted relative differences in HPV type-specific prevalence and 95% confidence intervals (CIs) were calculated by comparing individuals screened between 2007 and 2009 (n = 95 915) with individuals screened between 2013 and 2016 (n = 103 371). Weighted logistic regression was used to estimate relative risk of type-specific HPV infections. Tests of significance were 2-sided.
Genotype-specific prevalence fell with statistical signficance for HPV-16 (relative difference = ‒52.6%, 95% CI = ‒56.9 to ‒48.3), HPV-18 (relative difference = ‒62.1%, 95% CI = ‒68.5 to ‒55.8), HPV-31 (relative difference = ‒34.2%, 95% CI = ‒42.1 to ‒26.3), and HPV-33 (relative difference = ‒31.8%, 95% CI = ‒48.4 to ‒15.1). The relative difference increased for other carcinogenic HPV types by 19.5% (95% CI = 14.3 to 24.6) when excluding HPV-16/18. Large reductions in HPV-6/11 relative differences were observed, but overall, noncarcinogenic, nonvaccine types increased. Comparing female individuals born in 1996 with female individuals born in 1989, risk of infection with HPV-6, 11, 16, and 18 decreased by 80.0% among individuals aged 21-25 years. High-grade squamous intraepithelial lesions or worse decreased by 49.4% when extending the evaluation from 2007 to 2018.
The incidence of high-grade squamous intraepithelial lesions or worse is decreasing, with large reductions in the prevalence of quadrivalent HPV vaccine types and nonvaccine types HPV-31 and HPV-33, reflecting vaccine cross-protection. Increases in nonvaccine HPV genotypes may attenuate anticipated reductions in HPV-related abnormalities, including cancers, but the benefits of HPV vaccination remain substantial.
多项研究报告了人乳头瘤病毒(HPV)疫苗的影响。在此,我们呈现了美国实施四价HPV疫苗(HPV-6/11/16/18)后十年间基于人群的最大规模特定基因型分布调查。
对新墨西哥州15至30岁接受宫颈筛查的个体的液基宫颈细胞学样本进行广谱HPV基因分型检测。通过比较2007年至2009年筛查的个体(n = 95915)与2013年至2016年筛查的个体(n = 103371),计算HPV特定类型流行率的加权相对差异及95%置信区间(CI)。采用加权逻辑回归估计特定类型HPV感染的相对风险。显著性检验为双侧检验。
HPV-16(相对差异 = -52.6%,95% CI = -56.9至-48.3)、HPV-18(相对差异 = -62.1%,95% CI = -68.5至-55.8)、HPV-31(相对差异 = -34.2%,95% CI = -42.1至-26.3)和HPV-33(相对差异 = -31.8%,95% CI = -48.4至-15.1)的特定基因型流行率有统计学意义的下降。排除HPV-16/18后,其他致癌性HPV类型的相对差异增加了19.5%(95% CI = 14.3至24.6)。观察到HPV-6/11的相对差异大幅下降,但总体而言,非致癌、非疫苗类型增加。将1996年出生的女性个体与1989年出生的女性个体进行比较,21至25岁个体中HPV-6、11、16和18的感染风险降低了80.0%。将评估从2007年延长至2018年时,高级别鳞状上皮内病变或更严重病变减少了49.4%。
高级别鳞状上皮内病变或更严重病变的发生率正在下降,四价HPV疫苗类型以及非疫苗类型HPV-31和HPV-33的流行率大幅降低,这反映了疫苗的交叉保护作用。非疫苗HPV基因型的增加可能会削弱HPV相关异常(包括癌症)预期的减少,但HPV疫苗接种的益处仍然很大。