Escuela de Microbiología, Facultad de Ciencias, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras.
Prevention and Implementation Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.
Int J Cancer. 2019 Oct 15;145(8):2042-2050. doi: 10.1002/ijc.32156. Epub 2019 Feb 19.
HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV-tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow-up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18-related HSIL+ was 96.8% (95%CI = 83.8-99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3-68.6). Specificity was 97.5% (95%CI = 93.7-99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18-related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.
HPV 检测是宫颈癌筛查的更好选择,但 HPV 阳性女性的分流还需要额外的程序。HPV 编码的癌蛋白 E6 和 E7 作为 HPV 致癌性的主要效应物,代表了有前途的分流替代物。为了评估该检测的性能,我们纳入了来自筛查研究的 155 名女性和来自同一转诊人群的 59 名接受阴道镜检查且有癌前病变的女性。所有女性均接受了 HC2 检测和 LiPA 基因分型,并对宫颈拭子进行了 HPV16/18 E6 癌蛋白检测。对组织学标本进行了回顾,并使用 p16 免疫组化进行了裁决,55 名女性有明确的组织学 HSIL,31 名(56.3%)与 HPV16/18 相关,23 名与其他 HPV 类型相关,1 名 HPV 阴性。以组织学 HSIL/癌症为金标准估计了敏感性和特异性。E6 癌蛋白可在所有 HSIL 中检测到,除了一个,也可在所有检测到 HPV16/18 DNA 的癌症中检测到,但在与其他 HPV 类型或 HPV 阴性相关的病例中均未检测到。在最初无 HSIL 的少数 HPV16/18 DNA 阳性者(n=4)中,E6 癌蛋白阳性,在可获得信息的 3 例中有 2 例在随访中发现了癌前病变。HPV16/18 相关 HSIL+的估计敏感性为 96.8%(95%CI=83.8-99.8),而无论 HPV 类型如何,所有 HSIL+的敏感性为 56.4%(95%CI=43.3-68.6)。特异性为 97.5%(95%CI=93.7-99.0)。在这个之前筛查有限的洪都拉斯人群中,E6 癌蛋白被证明是一种高度敏感和特异的 HPV16/18 相关 HSIL 病变检测标志物,可作为筛查方案中的一种分流方法,特别是在低收入国家。