Serrano-Villar Sergio, Hernández-Novoa Beatriz, de Benito Amparo, Del Romero Jorge, Ocampo Antonio, Blanco José Ramón, Masiá Mar, Sendagorta Elena, Sanz Gonzalo, Moreno Santiago, Pérez-Molina José A
Department of Infectious Diseases, Facultad de Medicina, Hospital Unversitario Ramón y Cajal, Universidad de Alcalá, IRYCIS, Madrid, Spain.
Department of Histopathology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
PLoS One. 2017 Nov 30;12(11):e0188851. doi: 10.1371/journal.pone.0188851. eCollection 2017.
Screening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal lesions.
Cross-sectional multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV-infected MSM. We compared the diagnostic performance of an abnormal anal cytology and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression and comparison of ROC areas.
We included 328 HIV-infected MSM. HSIL was histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low sensitivity (41.2%) and specificity (71%). The combination of standard cytology with P16/Ki67 immunostaining did not increment the predictive value of standard cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688).
In HIV-infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous HSIL are warranted.
对感染HIV的男男性行为者进行肛门癌筛查时，肛门细胞学检查会导致较高的假阳性率以及高分辨率肛门镜检查负担增加。高危型人乳头瘤病毒（HPV）会上调上皮细胞中p16和Ki67的表达。我们评估了P16/Ki-67免疫染色细胞学检查在诊断肛门癌前病变中的作用。
横断面多中心研究。对感染HIV的男男性行为者同时进行p16/Ki-67免疫染色的肛门液基细胞学检查以及对醋酸白碘阴性病变进行活检的高分辨率肛门镜检查（HRA）。我们通过逻辑回归和ROC曲线下面积比较，对比了异常肛门细胞学检查和P16/Ki-67免疫染色相对于HRA引导活检的诊断性能。
我们纳入了328名感染HIV的男男性行为者。组织学诊断为高级别鳞状上皮内病变（HSIL）的有72例（25.1%），诊断为肛门癌的有2例（0.6%）。对于经活检证实的HSIL诊断，异常细胞学检查的敏感性为95.6%，特异性为58.8%。P16/Ki67阳性与经活检证实的HSIL存在相关（P趋势 = 0.004），但敏感性较低（41.2%），特异性为（71%）。标准细胞学检查与P16/Ki-67免疫染色联合使用并未提高单独标准细胞学检查的预测价值（AUC分别为0.685和0.673，P = 0.688）。
在感染HIV的男男性行为者中，P16/Ki-67免疫染色并不能提高肛门细胞学检查的诊断准确性，肛门细胞学检查敏感性高但特异性差。有必要采取其他方法来提高当前技术对癌前HSIL诊断的准确性。
