Bergeron Christine, Ronco Guglielmo, Reuschenbach Miriam, Wentzensen Nicolas, Arbyn Marc, Stoler Mark, von Knebel Doeberitz Magnus
Laboratoire Cerba, 95066 Cergy Pontoise Cedex 9, France.
Int J Cancer. 2015 Jun 15;136(12):2741-51. doi: 10.1002/ijc.28900. Epub 2014 May 12.
Cervical cancer screening test performance has been hampered by either lack of sensitivity of Pap cytology or lack of specificity of Human Papillomavirus (HPV) testing. This uncertainty can lead to unnecessary referral and treatment, which is disturbing for patients and increases costs for health care providers. The identification of p16(INK4a) as a marker for neoplastic transformation of cervical squamous epithelial cells by HPVs allows the identification of HPV-transformed cells in histopathology or cytopathology specimens. Diagnostic studies have demonstrated that the use of p16(INK4a) immunohistochemistry substantially improves the reproducibility and diagnostic accuracy of histopathologic diagnoses. p16(INK4a) cytology has substantially higher sensitivity for detection of cervical precancer in comparison to conventional Pap tests. Compared to HPV DNA tests, immunochemical detection of p16(INK4a) -stained cells demonstrates a significantly improved specificity with remarkably good sensitivity. About 15 years after the initial observation that p16(INK4a) is overexpressed in HPV-transformed cells we review the accumulated clinical evidence suggesting that p16(INK4a) can serve as a useful biomarker in the routine diagnostic work up of patients with HPV infections and associated lesions of the female anogenital tract.
宫颈癌筛查测试的性能受到巴氏细胞学敏感性不足或人乳头瘤病毒（HPV）检测特异性不足的阻碍。这种不确定性可能导致不必要的转诊和治疗，这对患者来说令人不安，并增加了医疗保健提供者的成本。p16（INK4a）作为HPV导致宫颈鳞状上皮细胞肿瘤转化的标志物，使得在组织病理学或细胞病理学标本中能够识别HPV转化的细胞。诊断研究表明，使用p16（INK4a）免疫组织化学可显著提高组织病理学诊断的可重复性和诊断准确性。与传统巴氏试验相比，p16（INK4a）细胞学对宫颈上皮内瘤变的检测具有显著更高的敏感性。与HPV DNA检测相比，对p16（INK4a）染色细胞的免疫化学检测显示特异性显著提高，敏感性也非常好。在首次观察到p16（INK4a）在HPV转化细胞中过度表达约15年后，我们回顾了积累的临床证据，表明p16（INK4a）可作为一种有用的生物标志物，用于对HPV感染及女性肛门生殖道相关病变患者进行常规诊断检查。
