Lega Italiana per la Lotta ai Tumori, Provincial Section of Latina, Italy.
Int J Cancer. 2014 Feb 15;134(4):897-904. doi: 10.1002/ijc.28407. Epub 2013 Aug 29.
P16-INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high-grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy-guided biopsy were included in the study; women surgically treated or having a CIN2-3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow-up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16-negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19-75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7-17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3-14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6-47.5). P16 overexpression is a good candidate for modulating follow-up intensity after a negative colposcopy but is limited by its low prospective sensitivity.
P16-INK4A 的过表达被提议作为一种预后标志物，用于管理细胞学和/或 HPV 检测阳性但无高级别宫颈上皮内瘤变（CIN2+）的女性的随访。本研究测量了这些女性中 p16 阳性与阴性的 CIN2+的相对风险（RR）。所有于 2008 年 10 月至 2010 年 9 月因阴性或 CIN1 阴道镜引导活检而转诊阴道镜的女性均纳入研究；排除手术治疗或 CIN2-3 的女性。所有基线活检均用苏木精和伊红以及 p16 染色。根据筛查方案对女性进行随访，在 6 或 12 个月时进行细胞学或阴道镜检查。计算 CIN2/3 的 RR 和 95%置信区间（95%CI）。在 442 名符合条件的女性中，有 369 名（83.5%）至少有一次随访。在基线时，113 名（30.6%）为 CIN1，248 名（67.2%）为阴性，8 名（2.2%）为组织学不足；293 名（79.4%）为 p16 阴性，64 名（17.3%）为 p16 阳性，12 名（3.2%）为无效。在随访期间，我们发现了 10 例 CIN2 和 3 例 CIN3；其中 6 例为 p16 阳性（敏感性 46%，95%CI 19-75）。p16 阳性患者的绝对风险为 9.4/100，而 p16 阴性患者为 1.7/100（RR 5.5；95%CI 1.7-17.4）。与组织学阴性的女性相比，CIN1 的风险更高（RR 4.4；95%CI 1.3-14.3）。CIN1 中 p16 的 RR 没有变化（RR 5.2；95%CI 0.6-47.5）。p16 过表达是在阴性阴道镜检查后调整随访强度的一个很好的候选标志物，但由于其前瞻性敏感性较低而受到限制。
