Department of Pathology, University of Virginia, Charlottesville, VA.
Am J Surg Pathol. 2018 Feb;42(2):192-200. doi: 10.1097/PAS.0000000000000974.
Cervical low-grade squamous intraepithelial lesions (LSIL) (aka cervical intraepithelial neoplasia, grade 1 [CIN1]) can present considerable diagnostic challenges and are associated with poor interobserver reproducibility and overdiagnosis. Furthermore, ancillary studies such as p16 immunohistochemistry have shown little utility in resolving the LSIL versus negative/reactive differential. Human papillomavirus (HPV) RNA in situ hybridization (ISH) has shown promise as a diagnostic aid in this setting, but has not been studied in a large case series. We herein investigate high-risk and low-risk HPV RNA ISH in 126 cervical biopsies originally diagnosed as LSIL/CIN1 and compare HPV RNA ISH results to expert-adjudicated morphologic diagnosis to assess whether this assay can help routine cases attain the existing "gold standard" of morphologic consensus diagnosis. We also assess whether this criterion standard can be further improved by integration of HPV RNA ISH results. A consensus diagnosis of intraepithelial lesion (CIN1) was confirmed in 61% of cases, whereas 57% were HPV RNA. HPV-RNA positivity was 84% sensitive and 86% specific for an expert-adjudicated diagnosis of CIN1. Conversely, consensus diagnosis was 90% sensitive and 78% specific for the presence of HPV RNA. Integrating RNA ISH into morphologic review led to further reclassification of 10% of cases, resulting in 95% sensitivity and 98% specificity of HPV RNA ISH for a CIN1 diagnosis and 98% sensitivity and 92% specificity of CIN1 for the presence of HPV RNA. These findings suggest that judicious use of HPV RNA ISH can improve the accuracy of LSIL/CIN1 diagnosis for morphologically ambiguous cases.
宫颈低级别鳞状上皮内病变（LSIL）（又称宫颈上皮内瘤变 1 级 [CIN1]）可能存在相当大的诊断挑战，并且与观察者间重复性差和过度诊断相关。此外，辅助研究，如 p16 免疫组化，在解决 LSIL 与阴性/反应性差异方面显示出很少的作用。人乳头瘤病毒（HPV）RNA 原位杂交（ISH）已显示出作为该情况下的诊断辅助手段的潜力，但尚未在大型病例系列中进行研究。在此，我们调查了最初诊断为 LSIL/CIN1 的 126 例宫颈活检中的高危和低危 HPV RNA ISH，并将 HPV RNA ISH 结果与专家裁决的形态学诊断进行比较，以评估该检测是否可以帮助常规病例达到现有的形态学共识诊断“金标准”。我们还评估了通过整合 HPV RNA ISH 结果是否可以进一步改善该标准。在 61%的病例中，上皮内病变（CIN1）的共识诊断得到确认，而 57%的病例为 HPV RNA。HPV-RNA 阳性对专家裁决的 CIN1 诊断的敏感性为 84%，特异性为 86%。相反，共识诊断对 HPV RNA 的存在的敏感性为 90%，特异性为 78%。将 RNA ISH 纳入形态学审查可导致 10%的病例进一步重新分类，从而使 HPV RNA ISH 对 CIN1 诊断的敏感性为 95%，特异性为 98%，HPV RNA 对 CIN1 的敏感性为 98%，特异性为 92%。这些发现表明，明智地使用 HPV RNA ISH 可以提高对形态学不明确病例的 LSIL/CIN1 诊断的准确性。
