Dr. Steinberg und Partner, Laboratory for Cytopathology, Im Stiftsfeld 1, 59494 Soest, Germany.
J Clin Virol. 2009 Nov;46 Suppl 3:S11-5. doi: 10.1016/S1386-6532(09)70295-1.
In Germany, cervical cancer screening is regulated by the German Federal Ministry of Health and Social Security and is available for all women from the age of 20 on the basis of the Papanicolaou (PAP) smear. The purpose of this study was to determine the positive predictive value of HR-HPV testing for precancerous lesions of the cervix uteri. Therefore, this study especially focused on the diagnostic accuracy of testing for one or more of the HPV types 16, 18 and 45 for all HR-HPV positive women, since HR-HPV infections with subtypes 16, 18 and 45 have demonstrated a higher risk of developing cervical cancer [Bulk S, et al. Br J Cancer 2006; 94:171-5].
Between 2007 and 2008 a total of 586 women were recruited: a group of 477 women with a history of known cervical lesions and/or HPV infections (eligibility criterion: HR-HPV DNA positive test result with HC2T) and a group of 109 women who were examined as part of their routine cervical cancer screening. Baseline HR-HPV status was measured at enrollment with the FDA-approved Hybrid Capture(R) 2 HPV DNA Test and the HR-HPV 16/18/45 Probe Set Test (HC2T, PST; QIAGEN, Hilden, Germany). Both tests use hybrid capture hybridization genotyping technology. Cervical smears were classified according to the Second Munich Nomenclature (1989). The results were converted to the nearest equivalent in the Bethesda system. In general, study subjects were followed up semiannually for a period of 1(1/2) years. The histopathological endpoint of CIN 2-3 lesion was used as a surrogate endpoint.
Preliminary data for 194 women of the risk group (43.5%) and for the complete control group were available. To date, CIN 2-3 was confirmed in 77 HR-HPV DNA positive women. 85.7% of these lesions were positive for one or more of the HR-HPV types 16, 18 and 45 (PST+). 88.2% (60/68) of the histologically confirmed CIN 3 lesions and six out of nine (66.6%) CIN 2 lesions were positive PST+. Furthermore, all women with a histologically confirmed squamous cell carcinoma (n = 4) were PST+. Besides, three (50%) out of six detected CIN 1 lesions were PST+. Nonetheless, histology confirmed no malignancy in three cases. Two of them were PST+.
These preliminary results demonstrate that starting cervical cancer screening at the age of 20 years remains important as seventeen (25%) of the 68 histologically verified CIN 3 lesions arose in women who were younger than 30 years. Furthermore, our data suggest that adding an HR-HPV test that detects one or more of the HR-HPV types 16, 18 and 45 in conjunction with cytology could help to identify women with an underlying cervical lesion who have an elevated risk of developing severe cervical lesions. This might offer the opportunity of a decrease in incidence and mortality rates that are related with invasive cervical cancer.
在德国，宫颈癌筛查由德国联邦卫生部和社会保障部监管，所有 20 岁以上的女性均可根据巴氏涂片（PAP 涂片）进行筛查。本研究的目的是确定 HR-HPV 检测对子宫颈癌前病变的阳性预测值。因此，本研究特别关注针对所有 HR-HPV 阳性女性检测 HPV 型 16、18 和 45 中的一种或多种的诊断准确性，因为 HPV 型 16、18 和 45 的 HR-HPV 感染显示出更高的宫颈癌发病风险[Bulk S, 等。Br J Cancer 2006; 94:171-5]。
2007 年至 2008 年间共招募了 586 名女性：一组 477 名有已知宫颈病变和/或 HPV 感染史的女性（入选标准：HC2T 检测到 HR-HPV DNA 阳性结果）和一组 109 名作为常规宫颈癌筛查一部分接受检查的女性。在入组时使用美国食品和药物管理局批准的杂交捕获（R）2 HPV DNA 检测和 HR-HPV 16/18/45 探针集检测（HC2T、PST；QIAGEN，Hilden，德国）测量基线 HR-HPV 状态。这两种检测都使用杂交捕获杂交基因分型技术。宫颈涂片根据慕尼黑第二命名法（1989 年）进行分类。结果转换为贝塞斯达系统中最接近的等效物。一般来说，研究对象每半年随访一次，随访时间为 1（1/2）年。CIN 2-3 病变的组织病理学终点被用作替代终点。
风险组（43.5%）和完整对照组的 194 名女性的初步数据可用。迄今为止，77 名 HR-HPV DNA 阳性女性已确诊为 CIN 2-3。这些病变中有 85.7%（60/68）为 HR-HPV 型 16、18 和 45（PST+）阳性。68 例组织学确诊的 CIN 3 病变中有 88.2%（60/68）和 9 例 CIN 2 病变中有 6 例（66.6%）为 PST+阳性。此外，所有组织学确诊的鳞状细胞癌（n=4）患者均为 PST+阳性。此外，在 6 例检测到的 CIN 1 病变中有 3 例（50%）为 PST+。尽管如此，组织学在 3 例中并未证实存在恶性肿瘤。其中 2 例为 PST+。
这些初步结果表明，从 20 岁开始进行宫颈癌筛查仍然很重要，因为 68 例组织学证实的 CIN 3 病变中有 17 例（25%）发生在年龄小于 30 岁的女性中。此外，我们的数据表明，联合细胞学检测，增加检测 HPV 型 16、18 和 45 中的一种或多种的 HR-HPV 检测，可能有助于识别具有潜在宫颈病变且发生严重宫颈病变风险增加的女性。这可能提供机会降低与侵袭性宫颈癌相关的发病率和死亡率。
