Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark; NIDO | Centre for Research and Education, Gødstrup Hospital, Herning, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark; NIDO | Centre for Research and Education, Gødstrup Hospital, Herning, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
Am J Obstet Gynecol. 2024 Apr;230(4):430.e1-430.e11. doi: 10.1016/j.ajog.2023.11.1235. Epub 2023 Dec 30.
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.
许多国家已经实施了积极监测（即不治疗病变）作为年轻的宫颈上皮内瘤变 2 级患者的选择之一，因为病变消退率较高，而切除治疗会增加后续妊娠中早产的风险。然而，早期识别有进展为宫颈上皮内瘤变 3 级或更高级别风险的女性很重要，以确保及时治疗。因为接种了人乳头瘤病毒疫苗的女性宫颈癌风险较低，因此她们未治疗的宫颈上皮内瘤变 2 级进展为宫颈上皮内瘤变 3 级或更高级别风险的可能性较低。
本研究旨在调查接种了人乳头瘤病毒疫苗并正在接受宫颈上皮内瘤变 2 级积极监测的女性与未接种疫苗的女性相比，在 28 个月的随访期间进展为宫颈上皮内瘤变 3 级或更高级别风险的可能性是否较低。
我们在丹麦进行了一项基于人群的队列研究，使用国家健康登记数据。我们确定了自 2007 年 1 月 1 日至 2020 年 12 月 31 日期间接受宫颈上皮内瘤变 2 级积极监测的 18 至 40 岁的所有女性。有宫颈上皮内瘤变 2 级或更高级别病史、子宫切除术或环形电切术的女性被排除在外。暴露定义为至少在宫颈上皮内瘤变 2 级诊断前 1 年接受过至少 1 剂人乳头瘤病毒疫苗。我们使用累积发病率函数估计在 28 个月内通过子宫切除术、移民和死亡作为竞争事件进展为宫颈上皮内瘤变 3 级或更高级别的风险。我们使用修正泊松回归计算 28 个月监测期间进展的粗和调整相对风险。结果按接种年龄分层，并调整了索引细胞学、可支配收入和教育水平。
该研究人群包括 7904 名女性，其中 3867 名（48.9%）在诊断为宫颈上皮内瘤变 2 级前至少 1 年接种了疫苗。在宫颈上皮内瘤变 2 级诊断时，接种疫苗的女性年龄较小（中位年龄 25 岁；四分位间距 23-27 岁），而未接种疫苗的女性年龄较大（中位年龄 29 岁；四分位间距 25-33 岁）。在 28 个月的随访期间，接种疫苗的女性发生宫颈上皮内瘤变 3 级或更高级别的 28 个月累积风险明显低于未接种疫苗的女性（22.9%；95%置信区间，19.8-26.1）和 15 至 20 岁之间（31.5%；95%置信区间，28.8-34.3）。因此，与未接种疫苗的女性相比，15 岁以下接种疫苗的女性进展为宫颈上皮内瘤变 3 级或更高级别的风险降低了 35%（调整后的相对风险，0.65；95%置信区间，0.57-0.75），而 15 至 20 岁之间接种疫苗的女性降低了 14%（调整后的相对风险，0.86；95%置信区间，0.79-0.95）。对于 20 岁以后接种疫苗的女性，与未接种疫苗的女性相比，风险相似（调整后的相对风险，1.02；95%置信区间，0.96-1.09）。
与未接种疫苗但在 20 岁之前接种疫苗的女性相比，在 28 个月的随访期间，正在接受宫颈上皮内瘤变 2 级积极监测且接种了疫苗的女性进展为宫颈上皮内瘤变 3 级或更高级别的风险较低。这些发现可能表明，人乳头瘤病毒疫苗接种状况可用于宫颈上皮内瘤变 2 级的临床管理中的风险分层。
