Columbia University, New York City, NY, USA.
Roche Molecular Systems, Inc., Pleasanton, CA, USA.
Gynecol Oncol. 2017 Jan;144(1):51-56. doi: 10.1016/j.ygyno.2016.10.031. Epub 2016 Oct 27.
In addition to genotyping for HPV16/18, dual-immunostaining for p16/Ki-67 has shown promise as a triage of HPV-positive women. We assessed the performance of p16/Ki-67 dual-stained cytology for triaging HPV-positive women undergoing primary HPV screening.
All women ≥25years with valid cervical biopsy and cobas® HPV Test results from the cross-sectional phase of ATHENA who were referred to colposcopy (n=7727) were eligible for enrolment. p16/Ki-67 dual-stained cytology was retrospectively performed on residual cytologic material collected into a second liquid-based cytology vial during the ATHENA enrolment visit. The diagnostic performance of dual-stained cytology, with or without HPV16/18 genotyping, for the detection of biopsy-confirmed cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was determined and compared to Pap cytology. Furthermore, the number of colposcopies required per CIN3+ detected was determined.
Dual-stained cytology was significantly more sensitive than Pap cytology (74.9% vs. 51.9%; p<0.0001) for triaging HPV-positive women, whereas specificity was comparable (74.1% vs. 75.0%; p=0.3198). Referral of all HPV16/18 positive women combined with dual-stained cytology triage of women positive for 12 "other" HPV genotypes provided the highest sensitivity for CIN3+ (86.8%; 95% CI: 81.9-90.8). A similar strategy but using Pap cytology for the triage of women positive for 12 "other" HPV genotypes was less sensitive (78.2%; 95% CI: 72.5-83.2; p=0.0003), but required a similar number of colposcopies per CIN3+ detected.
p16/Ki-67 dual-stained cytology, either alone or combined with HPV16/18 genotyping, represents a promising approach as a sensitive and efficient triage for colposcopy of HPV-positive women when primary HPV screening is utilized.
除了 HPV16/18 基因分型外，p16/Ki-67 双重免疫染色作为 HPV 阳性女性的分流方法也显示出了一定的前景。我们评估了 p16/Ki-67 双重染色细胞学在 HPV 初筛阳性女性中的应用效果。
所有年龄≥25 岁且在 ATHENA 的横断面阶段有有效宫颈活检和 cobas® HPV 检测结果，并被转诊行阴道镜检查的女性（n=7727）均符合入组条件。ATHENA 入组就诊时，使用剩余的液基细胞学标本进行 p16/Ki-67 双重染色细胞学检查。检测双重染色细胞学（无论是否进行 HPV16/18 基因分型）对活检证实的宫颈上皮内瘤变 3 级或更高级别（CIN3+）的诊断性能，并与巴氏涂片进行比较。此外，还确定了每例 CIN3+检测所需的阴道镜检查数量。
双重染色细胞学对 HPV 阳性女性的分流显著优于巴氏涂片（74.9% vs. 51.9%；p<0.0001），而特异性相当（74.1% vs. 75.0%；p=0.3198）。将所有 HPV16/18 阳性女性转诊，并对 12 种“其他”HPV 基因型阳性的女性进行双重染色细胞学分流，可获得最高的 CIN3+检出率（86.8%；95%CI：81.9-90.8）。采用相似的策略，但对 12 种“其他”HPV 基因型阳性的女性使用巴氏涂片进行分流，则敏感性较低（78.2%；95%CI：72.5-83.2；p=0.0003），但每例 CIN3+检测所需的阴道镜检查数量相似。
p16/Ki-67 双重染色细胞学，无论是单独使用还是与 HPV16/18 基因分型联合使用，当进行 HPV 初筛时，都是一种很有前途的、能够敏感而高效地对 HPV 阳性女性进行阴道镜检查的分流方法。
