Kapi'olani Medical Center for Women and Children, Honolulu, HI.
J Low Genit Tract Dis. 2014 Jan;18(1):1-7. doi: 10.1097/LGT.0b013e31828aeb39.
The current system of Pap smear screening and management of abnormal cytology has resulted in a marked reduction in invasive cervical cancer. Many women, however, are not found to have significant precursor lesions. This is due to the poor specificity of high-risk human papillomavirus (HPV) triage. More specific cervical cancer biomarkers may be more effective triage tools than hr-HPV. We evaluated whether a dual stain for p16 and Ki-67 might improve the triage of abnormal Pap smears.
p16/Ki-67 immunostaining was performed on additional slides prepared from 515 women with abnormal Pap smears (301 atypical squamous cells of undetermined significance [ASCUS], 169 low-grade squamous intraepithelial lesion [LSIL], 29 atypical squamous cells-cannot exclude high-grade lesion [ASC-H], 16 high-grade squamous intraepithelial lesion [HSIL]). High-risk HPV typing was performed on all cases. Immunostaining and hr-HPV were compared in relation to their diagnostic accuracy for the detection of biopsy-proven cervical intraepithelial neoplasia (CIN) 2/3. A cost analysis comparing hr-HPV versus immunostaining as the initial triage tool used for abnormal Pap smears was also performed.
High-risk HPV was positive in 127 (42.2%) ASCUS, 129 (76.3%) LSIL, 20 (69.0%) ASC-H, and 15 (93.8%) HSIL. p16/Ki-67 was positive in 54 (17.9%) ASCUS, 73 (43.2%) LSIL, 19 (65.5%) ASC-H, and 15 (93.8%) HSIL. For detection of CIN 2/3, sensitivity/specificity of hr-HPV and p16/Ki-67 was 89.29%/14.94% and 96.43%/60.92%, respectively. Overall, diagnostic accuracy was statistically significantly higher for p16/Ki-67 compared with hr-HPV. Compared to HPV, immunostain triage could have generated approximately $46,000 savings in the study population.
The triage of abnormal Pap smears by p16/Ki-67 immunostaining shows comparable sensitivity, improved specificity, and significantly improved diagnostic performance when compared to hr-HPV. Immunostaining is of value in triaging LSIL and ASC-H Pap smears in addition to ASCUS. The widespread utilization of biomarker triage could result in significant health care cost savings without compromising the detection of significant cervical cancer precursors.
巴氏涂片筛查和异常细胞学管理系统显著降低了宫颈癌的发病率。然而，许多女性并未发现有明显的前驱病变。这是由于高危型人乳头瘤病毒（HPV）分流的特异性差。更特异的宫颈癌生物标志物可能是比 HR-HPV 更有效的分流工具。我们评估了 p16 和 Ki-67 的双重染色是否能改善异常巴氏涂片的分流。
对 515 例巴氏涂片异常（301 例非典型鳞状细胞意义不明确[ASCUS]、169 例低度鳞状上皮内病变[LSIL]、29 例非典型鳞状细胞-不能排除高级别病变[ASC-H]、16 例高级别鳞状上皮内病变[HSIL]）的妇女的额外玻片进行了 p16/Ki-67 免疫染色。对所有病例进行高危型 HPV 分型。比较了免疫染色和 HR-HPV 在检测活检证实的宫颈上皮内瘤变（CIN）2/3 方面的诊断准确性。还比较了 HR-HPV 与免疫染色作为异常巴氏涂片初始分流工具的成本分析。
127 例（42.2%）ASCUS、129 例（76.3%）LSIL、20 例（69.0%）ASC-H 和 15 例（93.8%）HSIL 的高危型 HPV 阳性。54 例（17.9%）ASCUS、73 例（43.2%）LSIL、19 例（65.5%）ASC-H 和 15 例（93.8%）HSIL 的 p16/Ki-67 阳性。对于 CIN 2/3 的检测，HR-HPV 和 p16/Ki-67 的敏感性/特异性分别为 89.29%/14.94%和 96.43%/60.92%。总体而言，p16/Ki-67 的诊断准确性明显高于 HR-HPV。与 HPV 相比，免疫染色分流在研究人群中可能节省约 46000 美元。
p16/Ki-67 免疫染色对异常巴氏涂片的分流具有相似的敏感性，特异性提高，与 HR-HPV 相比，诊断性能显著提高。免疫染色除了对 ASCUS 外，对 LSIL 和 ASC-H 巴氏涂片的分流也有价值。广泛应用生物标志物分流可以显著节省医疗保健费用，而不会影响对重要宫颈癌前体的检测。
