背景:许多国家已经实施了主动监视(即,保留病变不治疗)作为宫颈上皮内瘤变2级年轻女性的一种选择,因为消退率高,切除治疗会增加后续妊娠早产的风险。然而,早期发现宫颈上皮内瘤变3级或更严重的风险增加的女性对于确保及时治疗很重要.因为接受过人类乳头瘤病毒疫苗的女性患子宫颈癌的风险较低,未治疗的宫颈上皮内瘤变2级进展至宫颈上皮内瘤变3级或更严重的风险较低.
目的:本研究旨在调查与未接种人乳头瘤病毒疫苗的女性相比,接受宫颈上皮内瘤变2级主动监测的女性发展为宫颈上皮内瘤变3级或更差的可能性较小。
方法:我们在丹麦进行了一项基于人群的队列研究,使用来自国家健康登记的数据。我们确定了从2007年1月1日至2020年12月31日接受宫颈上皮内瘤变2级积极监测的所有18至40岁女性。既往有宫颈上皮内瘤变2级或更差记录的女性,子宫切除术,或环形电切术被排除。暴露定义为在宫颈上皮内瘤变2级诊断前至少1年接受≥1剂人乳头瘤病毒疫苗。我们使用累积发生率函数来估计28个月内使用子宫切除术进展为宫颈上皮内瘤变3级或更差的风险。移民,和死亡作为竞争事件。我们使用改进的泊松回归来计算28个月监测期内的粗略和调整的相对进展风险。结果按接种疫苗时的年龄进行分层,并根据细胞学指标进行调整,可支配收入,和教育水平。
结果:研究人群包括7904名女性,其中3867名(48.9%)在诊断为2级宫颈上皮内瘤变至少1年前接种了疫苗。在宫颈上皮内瘤变2级诊断时,接种疫苗的妇女年龄较小(中位年龄,25年;四分位数范围,23-27岁)比那些没有(中位年龄,29年;四分位数范围,25-33岁)。在15岁之前接种疫苗的妇女中,宫颈上皮内瘤变3级或更严重的28个月累积风险显着降低(22.9%;95%置信区间,19.8-26.1)和15至20岁之间的年龄(31.5%;95%的置信区间,28.8-34.3)与未接种疫苗的女性相比(37.6%;95%的置信区间,36.1–39.1).因此,与未接种疫苗的女性相比,那些在15岁之前接种疫苗的人进展为宫颈上皮内瘤变3级或更差的风险降低了35%(调整后的相对风险,0.65;95%置信区间,0.57-0.75),而年龄在15至20岁之间接种疫苗的女性风险降低了14%(调整后的相对风险,0.86;95%置信区间,0.79-0.95)。对于20岁后接种疫苗的女性,风险与未接种疫苗的女性相当(调整后的相对风险,1.02;95%置信区间,0.96-1.09)。
结论:与未接种疫苗但仅在20岁之前接种疫苗的女性相比,接种疫苗并正在接受宫颈上皮内瘤变2级积极监测的女性在28个月的随访期间进展为宫颈上皮内瘤变3级或更差的风险较低。这些发现可能表明,人乳头瘤病毒疫苗接种状态可用于2级宫颈上皮内瘤变的临床管理中的风险分层。
Many countries have implemented active surveillance (ie, leaving the lesion untreated) as an option among younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment increases the risk for preterm birth in subsequent pregnancies. However, early identification of women at increased risk for progression to cervical intraepithelial neoplasia grade 3 or worse is important to ensure timely treatment. Because women who have received a human papillomavirus vaccine have a lower risk for cervical cancer, they may have a lower risk for progression of untreated cervical intraepithelial neoplasia grade 2 to cervical intraepithelial neoplasia grade 3 or worse.
This
study aimed to investigate if women who received a human papillomavirus vaccine and who are undergoing active surveillance for cervical intraepithelial neoplasia grade 2 are less likely to progress to cervical intraepithelial neoplasia grade 3 or worse when compared with women who did not receive the vaccine.
We conducted a population-based cohort
study in Denmark using data from national health registers. We identified all women aged 18 to 40 years who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 from January 1, 2007, to December 31, 2020. Women with a previous record of cervical intraepithelial neoplasia grade 2 or worse, hysterectomy, or a loop electrosurgical excision procedure were excluded. Exposure was defined as having received ≥1 dose of a human papillomavirus vaccine at least 1 year before the cervical intraepithelial neoplasia grade 2 diagnosis. We used cumulative incidence functions to estimate the risk for progression to cervical intraepithelial neoplasia grade 3 or worse within 28 months using hysterectomy, emigration, and death as competing events. We used modified Poisson regression to calculate crude and adjusted relative risks of progression during the 28-month surveillance period. Results were stratified by age at vaccination and adjusted for index cytology, disposable income, and educational level.
The
study population consisted of 7904 women of whom 3867 (48.9%) were vaccinated at least 1 year before a diagnosis of cervical intraepithelial neoplasia grade 2. At the time of cervical intraepithelial neoplasia grade 2 diagnosis, women who were vaccinated were younger (median age, 25 years; interquartile range, 23-27 years) than those who were not (median age, 29 years; interquartile range, 25-33 years). The 28-month cumulative risk for cervical intraepithelial neoplasia grade 3 or worse was significantly lower among women who were vaccinated before the age of 15 years (22.9%; 95% confidence interval, 19.8-26.1) and between the ages of 15 and 20 years (31.5%; 95% confidence interval, 28.8-34.3) when compared with women who were not vaccinated (37.6%; 95% confidence interval, 36.1-39.1). Thus, when compared with women who were not vaccinated, those who were vaccinated before the age of 15 years had a 35% lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse (adjusted relative risk, 0.65; 95% confidence interval, 0.57-0.75), whereas women who were vaccinated between the ages of 15 and 20 years had a 14% lower risk (adjusted relative risk, 0.86; 95% confidence interval, 0.79-0.95). For women who were vaccinated after the age of 20 years, the risk was comparable with that among women who were not vaccinated (adjusted relative risk, 1.02; 95% confidence interval, 0.96-1.09).
Women who were vaccinated and who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 had a lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse during 28 months of follow-up when compared with women who were not vaccinated but only if the vaccine was administered by the age of 20 years. These findings may suggest that the human papillomavirus vaccination status can be used for risk stratification in clinical management of cervical intraepithelial neoplasia grade 2.