Cervical squamous intraepithelial lesions grades 1 and 2: value of an alternative morphological classification and of p16 immunohistochemistry in the prediction of clinical outcome

ABSTRACT Introduction: Diagnostic reproducibility and determination of prognostic factors in cervical intraepithelial neoplasias grades 1 and 2 are still relevant problems in the daily practice of gynecological histopathology. Objective: To correlate the value of morphological reclassification and of p16 immunoexpression in cervical intraepithelial neoplasias grades 1 and 2 with clinical outcome. Materials and methods: Sixty-six patients were included (34 with cervical intraepithelial neoplasia grade 1, and 32 with grade 2); an immunohistochemical study with p16 and reclassification according to the Lower Anogenital Squamous Terminology (LAST) Consensus and by the alternative proposal of Herfs and Crum were done; unfavorable outcome was defined as a subsequent histologic diagnosis of cervical intraepithelial neoplasia grade 3 or invasive squamous cell carcinoma. Results: We observed superior performance of the alternative morphological classification (p = 0.002) to determine unfavorable outcome. We also detected superior performance of p16 in the same determination (p = 0.002). Conclusion: The use of an alternative morphological classification is promising; in the context of the use of immunohistochemical antibodies as biomarkers, p16 showed good sensitivity and negative predictive value in the determination of cases in which the outcome was unfavorable.

摘要
引言：子宫颈上皮内瘤变1级与2级（cervical intraepithelial neoplasias grades 1 and 2）的诊断可重复性及预后因素判定，仍是妇科组织病理学日常实践中的常见难点问题。
目的：探讨子宫颈上皮内瘤变1级、2级的形态学重分类价值及p16免疫表达与临床结局的相关性。
材料与方法：纳入66例患者，其中34例为子宫颈上皮内瘤变1级，32例为子宫颈上皮内瘤变2级；开展p16免疫组化检测，并依据《肛门生殖器鳞状上皮术语共识（Lower Anogenital Squamous Terminology, LAST）》以及Herfs与Crum提出的替代方案进行重分类；不良结局定义为后续组织学确诊为子宫颈上皮内瘤变3级或浸润性鳞状细胞癌。
结果：替代形态学分类方案在判定不良结局方面展现出更优效能（p=0.002）；同时，p16检测在该项判定中同样具备更优效能（p=0.002）。
结论：采用替代形态学分类方案具有良好的应用前景；在以免疫组化抗体作为生物标志物的研究场景中，p16在判定不良结局病例时展现出良好的灵敏度与阴性预测值。