Lukic Ankica, Sbenaglia Giorgio, Carico Elisabetta, DI Properzio Matilde, Giarnieri Enrico, Frega Antonio, Nobili Flavia, Moscarini Massimo, Giovagnoli Maria Rosaria
Dipartimento Salute della Donna e Medicina Territoriale, UOC Ginecologia, Facoltà di Medicina e Psicologia, Sapienza Università di Roma, 00189 Rome;
Exp Ther Med. 2011 Sep;2(5):853-858. doi: 10.3892/etm.2011.316. Epub 2011 Jul 1.
p16INK4a as a diagnostic marker of a cervical intraepithelial neoplasia of grade 2+ (CIN2+) in atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytological samples has been analyzed, but has not yet been included in clinical routine practice. One hundred and ninety-one patients with an abnormal Pap test (84 ASC-US and 107 LSILs) who underwent colposcopy were selected for this study. At enrollment, 96 patients (Group 1) had a positive colposcopy and therefore underwent a cervical biopsy, while 95 (Group 2) had a negative colposcopy and were followed up for up to 1 year. Both groups were tested for p16INK4a using immunocytochemical methods, and the p16INK4a results were correlated with histology or follow-up outcome. In Group 1 ASC-US cases, 82% of lesions less than CIN2 were p16INK4a-negative and all CIN2 cases were p16INK4a-positive (p=0.00044). In Group 1 LSIL cases, 71% of lesions less than CIN2 were p16INK4a-negative and 87% of CIN2/3 were p16INK4a-positive (p=0.00033). Seventy-seven percent of Group 2 ASC-US patients with a negative 1-year follow-up (NF-U) were p16INK4a-negative at enrollment, while all patients with positive follow-up (PF-U) were p16INK4a-positive (p=0.00113). In Group 2 LSIL cases, 83% of patients with NF-U were p16INK4a-negative, while 65% of patients with PF-U were p16INK4a-positive at enrollment (p=0.0014). In fact, 39% of the positive p16INK4a LSIL patients had CIN2+ histological lesions. The positive predictive value of p16INK4a for CIN2+ was 50% in ASC-US and 52% in LSIL cases; the negative predictive value was 100 and 94%, respectively. In conclusion, in our patients, a negative p16INK4a appears to be a marker of the absence of CIN3, while a positive p16INK4a can be correlated with the presence of histological CIN2+ found at enrollment or during the subsequent follow-up. Thus, its clinical predictive value is independent from the colposcopic aspect at enrollment.
p16INK4a作为意义不明确的非典型鳞状细胞（ASC-US）和低级别鳞状上皮内病变（LSIL）细胞学样本中2级及以上宫颈上皮内瘤变（CIN2+）的诊断标志物已得到分析，但尚未纳入临床常规实践。本研究选取了191例接受阴道镜检查的巴氏试验异常患者（84例ASC-US和107例LSIL）。入组时，96例患者（第1组）阴道镜检查结果为阳性，因此接受了宫颈活检，而95例（第2组）阴道镜检查结果为阴性，并随访长达1年。两组均采用免疫细胞化学方法检测p16INK4a，p16INK4a结果与组织学或随访结果相关。在第1组ASC-US病例中，小于CIN2的病变82%为p16INK4a阴性，所有CIN2病例均为p16INK4a阳性（p=0.00044）。在第1组LSIL病例中，小于CIN2的病变71%为p16INK4a阴性，CIN2/3的病变87%为p16INK4a阳性（p=0.00033）。第2组中，1年随访阴性（NF-U）的ASC-US患者77%在入组时p16INK4a为阴性，而所有随访阳性（PF-U）的患者p16INK4a为阳性（p=0.00113）。在第2组LSIL病例中，NF-U的患者83%在入组时p16INK4a为阴性，而PF-U的患者65%在入组时p16INK4a为阳性（p=0.0014）。事实上，p16INK4a阳性的LSIL患者中39%有CIN2+组织学病变。p16INK4a对CIN2+的阳性预测值在ASC-US病例中为50%，在LSIL病例中为52%；阴性预测值分别为100%和94%。总之，在我们的患者中，p16INK4a阴性似乎是不存在CIN3的标志物，而p16INK4a阳性可能与入组时或后续随访中发现的组织学CIN2+有关。因此，其临床预测价值独立于入组时的阴道镜表现。
