Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Obstetrics and Gynecology, Gødstrup Hospital, Herning, Denmark.
Acta Obstet Gynecol Scand. 2023 Sep;102(9):1227-1235. doi: 10.1111/aogs.14627. Epub 2023 Jul 19.
Many countries have adopted active surveillance in women with cervical intraepithelial neoplasia grade 2 (CIN2), leaving the lesion untreated. However, there is a lack of consensus on the eligibility criteria for active surveillance across countries, with some abstaining from active surveillance in women with human papilloma virus 16 (HPV16) or a high-grade cytology. Here, we aimed to describe the distribution of HPV genotypes, age, and cytology in women undergoing active surveillance for CIN2.
We conducted a single-center cross-sectional study on women aged 23-40 undergoing active surveillance for CIN2 during 2000-2010. Women were identified through the Danish Pathology Data Bank (DPDB) at Aarhus University Hospital, Denmark. We collected information on basic characteristics and results of histopathological examinations via DPDB. Women were deemed eligible for inclusion if they had a subsequent biopsy after index CIN2, and had no prior record of CIN2+, hysterectomy, or cone biopsy. Archived biopsies underwent HPV genotyping using the HPV SPF - DEIA-LiPA system, and the diagnosis was re-evaluated by three expert pathologists. We used the Chi squared-test (p-value) for comparison across groups.
We identified 3623 women with CIN2 of whom 455 (12.6%) were included. Most women were 30 years or younger (73.8%), and half (48.8%) had a high-grade index cytology. The prevalence of any high-risk HPV was 87.0%, with HPV16 being the most prevalent genotype (35.6%). The prevalence of HPV16 was significantly higher in women aged 30 or younger (39.3%) compared to women older than 30 years (25.2%) (p = 0.006). Upon expert review, 261 (57.4%) had CIN2 confirmed, whereas 56 (12.3%) were upgraded to CIN3 and 121 (26.6%) were downgraded to CIN1/normal. While the HPV16 prevalence was similar between community and expert confirmed CIN2, the prevalence of HPV16 was significantly higher in women with expert CIN3 compared to women with expert CIN1/normal (64.3% vs. 19.0%, p = 0.001).
The high prevalence of HPV16 and high-grade cytology imply that these women may be perceived as a high-risk population and non-eligible for active surveillance in countries outside Denmark. Future studies should investigate the importance of HPV, age, cytology, and expert review on risk of progression to help refine criteria for active surveillance.
许多国家对宫颈上皮内瘤变 2 级（CIN2）患者采取了积极监测策略，不对病变进行治疗。然而，各国对积极监测的入选标准尚未达成共识，一些国家不将 HPV16 阳性或高级别细胞学异常的患者纳入积极监测。本研究旨在描述在接受 CIN2 积极监测的患者中 HPV 基因型、年龄和细胞学的分布情况。
我们对 2000 年至 2010 年期间在丹麦奥胡斯大学医院通过丹麦病理数据库（DPDB）识别的年龄在 23-40 岁之间、接受 CIN2 积极监测的女性进行了一项单中心横断面研究。我们通过 DPDB 收集了组织病理学检查的基本特征和结果信息。如果患者在索引 CIN2 后进行了后续活检，且无 CIN2+、子宫切除术或锥形切除术的既往记录，则认为符合纳入标准。对存档活检标本采用 HPV SPF-DEIA-LiPA 系统进行 HPV 基因分型，并由三位专家病理学家对诊断进行重新评估。我们使用卡方检验（p 值）比较组间差异。
我们共确定了 3623 例 CIN2 患者，其中 455 例（12.6%）纳入研究。大多数患者年龄在 30 岁或以下（73.8%），一半（48.8%）的高级别细胞学异常。高危型 HPV 阳性率为 87.0%，HPV16 是最常见的基因型（35.6%）。年龄在 30 岁或以下的患者中 HPV16 的阳性率明显高于 30 岁以上的患者（39.3%比 25.2%，p=0.006）。经专家评估，261 例（57.4%）为 CIN2 确诊患者，56 例（12.3%）升级为 CIN3，121 例（26.6%）降级为 CIN1/正常。社区诊断与专家确诊的 CIN2 患者中 HPV16 的阳性率相似，但专家确诊的 CIN3 患者中 HPV16 的阳性率明显高于专家确诊的 CIN1/正常患者（64.3%比 19.0%，p=0.001）。
HPV16 和高级别细胞学异常的高阳性率意味着这些患者可能被视为高危人群，不适合丹麦以外的国家将其纳入积极监测。未来的研究应探讨 HPV、年龄、细胞学和专家评估在疾病进展风险中的重要性，以帮助完善积极监测的入选标准。
