Previous studies of p16 immunohistochemistry (IHC) on CIN1 have suggested the likely utility of p16 in stratification of women at risk for subsequent CIN2/3. But those studies had limitations in statistical power, histologic diagnosis, and disease ascertainment. We conducted a retrospective study of p16 IHC on adjudicated CIN1 tissue diagnosed in young women participating in the placebo arm of the quadrivalent human papillomavirus (HPV) vaccine trials. Tissue sections were stained with p16 IHC and hematoxylin and eosin. p16 IHC was scored using LAST criteria, and hematoxylin and eosin-stained sections were reviewed for concordance with the adjudicated diagnosis. p16 IHC, antecedent high-grade cytology, review diagnosis, and HPV16 detection were assessed as independent risk factors for subsequent CIN2/3. Five hundred twenty-four patients with CIN1 biopsies and complete data were identified, 63 (12.0%) of whom developed CIN2/3 in follow-up. p16 positivity (P=0.06), review diagnosis of CIN2/3 (P=0.04), HPV16 positivity (P=0.01), and antecedent high-grade cytology (P=0.02) were (marginally) associated with CIN2/3. In a logistic regression model, the associations with CIN2/3 (vs. other), expressed as odds ratios (95% confidence intervals), were 1.6 (0.91-2.8) for p16, 2.0 (1.0-3.7) for HPV16, and 2.2 (1.1-2.4) for antecedent high-grade cytology. The mean risks for CIN2/3 estimated from the model ranged from 7.6% for negative for all markers to 36.3% for positive for all 3 markers. p16 IHC does not risk stratify CIN1 patients in a manner that would alter recommended management for CIN1. This reinforces the LAST recommendations that p16 should only be used selectively for problematic scenarios, such as CIN2 because of its inherent lack of reproducibility, cases in which one is struggling between CIN1 and CIN2, and benign mimics of CIN3.
以往对CIN 1所进行的p16免疫组织化学（IHC）研究提示， p16似可用于女性CIN1以及随后所发生的CIN2/3的危险分层中。但是，那些研究在统计学能力、组织学诊断以及疾病的认定方面具有一定局限性。我们对取自于参加四价HPV疫苗临床试验安慰剂组年轻女性的CIN1组织进行了p16 IHC回顾性研究。组织切片进行p16 IHC染色和HE染色。P16 IHC使用LAST标准进行评分，HE染色切片用来复审并判断前后诊断的一致性。P16 IHC、以往高级别细胞学病变、复审诊断以及HPV16检测是评估随后发生CIN2/3的独立危险因素。鉴定了524例患者的CIN1活检组织及完整的数据资料，随访中发现63例（12.0%）发展为CIN2/3。P16阳性（P=0.06）、复审诊断为CIN2/3（P=0.04）、HPV16阳性（P=0.01）以及以往高级别细胞学病变（P=0.02）与CIN2/3相关（尽管某些相关性稍差）。在对数回归模型中， p16、 HPV16以及以往高级别细胞学病变与 CIN2/3相比的相关性及OR值（95%可信区间）分别 为1.6（0.91-2.8）、2.0（1.0-3.7）、2.2（1.1-2.4）。根据模型估计的CIN2/3平均风险在所有指标都为阴性时为7.6%，三个指标都为阳性时为36.3%。p16 IHC不能对CIN 1患者进行危险分层进而改变CIN 1的推荐性治疗。这一研究结果补充了LAST的介绍内容，即p16仅可以选择性的使用于有疑问的情况，如缺乏内在活动性的CIN2、CIN1与CIN2之间难以确定的病例以及与CIN3相似的良性病变。