Sahlgren Hanna A I, Elfgren Kristina, Sparen Pär, Elfstrom Miriam K
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Obstetrics and Gynecology, Falun Hospital, Falun, Sweden; Regional Cancer Center Uppsala, Uppsala, Sweden.
Division of Obstetrics and Gynecology, Department of Clinical Science Intervention and Technology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
Am J Obstet Gynecol. 2022 May;226(5):704.e1-704.e9. doi: 10.1016/j.ajog.2021.11.1372. Epub 2021 Dec 23.
Sweden started subsidized quadrivalent human papillomavirus vaccination for girls aged 13 to 17 in 2007. Since 2012, vaccination has been offered to all girls aged 10 to 12 within a school-based vaccination program, with a coverage of 80% or more. In addition, the vaccine has been offered on-demand as catch-up vaccination for girls aged 13 to 18, with a cumulative coverage of 55% to 60%. Since the first women in Sweden eligible for human papillomavirus vaccination entered the cervical screening program, questions on how to evaluate colposcopic findings among vaccinated women have arisen. Evidence is inconsistent on whether colposcopic features for the detection of cervical lesions are influenced by specific human papillomavirus genotypes and what role they can play in the prevention of invasive cervical cancer in vaccinated women.
The primary objective of the study was to compare colposcopic evaluation in vaccinated and unvaccinated women entering the organized cervical screening program.
Women in the 1994 and 1995 birth cohorts who entered the cervical screening program at age 23 in 1 region in Sweden were identified. Colposcopy was performed within 2 to 4 months after a positive screening result in accordance with national guidelines. Colposcopic performance was evaluated according to national guidelines with the Swede score and colposcopic impression. Punch biopsies were taken from colposcopic lesions and as "random biopsies" in the absence of lesions. These biopsies were used as the gold standard for the analysis. An endocervical sample was analyzed for cytologic findings and detection of 14 high-risk human papillomavirus genotypes. All colposcopic imaging was saved digitally for re-review. Vaccination status was obtained through linkage to national vaccination registries. Results were compared between vaccinated and unvaccinated women.
In 2018 and 2019, 160 out of 165 (98%) women with a positive screening result attended colposcopy, of which 90 (56%) were vaccinated and 70 (44%) were unvaccinated. Only 7 out of 90 (5%) women in the vaccinated group were human papillomavirus 16/18-positive, compared with 23 out of 70 (33%) in the unvaccinated group (P<.001). There was a total of 61 out of 160 (38%) women with high-grade lesions-33 out of 90 (37%) in the vaccinated group and 28 out of 70 (40%) in the unvaccinated group (P=.697). There was 64% (21/33) of vaccinated women and 75% (21/28) of unvaccinated women with high-grade squamous intraepithelial lesions who had a Swede score of 6 to 10 (indicating high-grade squamous intraepithelial lesions) (P=.124). The sensitivity was slightly higher for the detection of high-grade squamous intraepithelial lesions in unvaccinated women using both colposcopic tests (Swede score, 0.67 vs 0.75; colposcopic impression, 0.67 vs 0.68), but the difference was not statistically significant.
We found no statistically significant difference between the colposcopic evaluation of vaccinated and unvaccinated women, although human papillomavirus vaccination reduced the prevalence of human papillomavirus 16/18 infection in human papillomavirus-vaccinated women. Our results indicate that colposcopic examination is still a useful tool in vaccinated women entering the organized cervical screening program.
瑞典于2007年开始为13至17岁的女孩提供四价人乳头瘤病毒疫苗接种补贴。自2012年起,在一项基于学校的疫苗接种计划中,为所有10至12岁的女孩提供疫苗接种,接种率达80%或更高。此外,还为13至18岁的女孩提供了按需补种疫苗,累计接种率为55%至60%。自瑞典首批符合人乳头瘤病毒疫苗接种条件的女性进入宫颈筛查计划以来,出现了如何评估接种疫苗女性的阴道镜检查结果的问题。关于检测宫颈病变的阴道镜特征是否受特定人乳头瘤病毒基因型影响以及它们在预防接种疫苗女性的浸润性宫颈癌中能发挥何种作用,证据并不一致。
本研究的主要目的是比较进入有组织的宫颈筛查计划的接种疫苗和未接种疫苗女性的阴道镜评估。
确定了1994年和1995年出生队列中于2018年在瑞典某一地区23岁时进入宫颈筛查计划的女性。根据国家指南,在筛查结果呈阳性后的2至4个月内进行阴道镜检查。根据国家指南,用瑞典评分和阴道镜印象评估阴道镜检查表现。从阴道镜病变处取活检组织,并在无病变时取“随机活检”组织。这些活检组织用作分析的金标准。对宫颈管样本进行细胞学检查和14种高危人乳头瘤病毒基因型的检测。所有阴道镜图像均进行数字保存以供复查。通过与国家疫苗接种登记处的关联获取疫苗接种状态。比较接种疫苗和未接种疫苗女性的结果。
在2018年和2019年,165名筛查结果呈阳性的女性中有160名(98%)接受了阴道镜检查,其中90名(56%)接种了疫苗,70名(44%)未接种疫苗。接种疫苗组的90名女性中只有7名(5%)人乳头瘤病毒16/18呈阳性,而未接种疫苗组的70名女性中有23名(33%)呈阳性(P<0.001)。160名女性中共有61名(38%)患有高级别病变,接种疫苗组的90名中有33名(37%),未接种疫苗组的70名中有28名(40%)(P=0.697)。高级别鳞状上皮内病变的接种疫苗女性中有64%(21/33)和未接种疫苗女性中有75%(21/28)的瑞典评分为6至10分(表明高级别鳞状上皮内病变)(P=0.124)。使用两种阴道镜检查方法检测未接种疫苗女性的高级别鳞状上皮内病变的敏感性略高(瑞典评分,0.67对0.75;阴道镜印象,0.67对0.68),但差异无统计学意义。
我们发现接种疫苗和未接种疫苗女性的阴道镜评估之间无统计学显著差异,尽管人乳头瘤病毒疫苗接种降低了接种疫苗女性中人乳头瘤病毒16/18感染的患病率。我们的结果表明阴道镜检查对于进入有组织的宫颈筛查计划的接种疫苗女性仍然是一种有用的工具。