Unit of Infections and Cancer, Cancer Epidemiology Research Programme, IDIBELL, Catalan Institute of Oncology, Av, Gran Vía, 199-203L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
BMC Infect Dis. 2012 Jan 26;12:25. doi: 10.1186/1471-2334-12-25.
A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US.
During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +.
Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions--HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women.
Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage.
2006 年，西班牙加泰罗尼亚引入了一项针对 25 至 65 岁有性生活女性的宫颈癌筛查方案，以提高覆盖率并建议将筛查细胞学检查的间隔时间延长至 3 年。此外，还为不明确意义的非典型鳞状细胞（ASC-US）诊断的女性提供了人乳头瘤病毒（HPV）作为分流试验。建议在 ASC-US 诊断后 3 个月内进行 HPV 检测。根据方案，HPV 阴性女性被转介至常规筛查，包括每 3 年进行一次细胞学检查，而 HPV 阳性女性则被转介至阴道镜检查和更密切的随访。我们评估了该方案的实施情况以及 HPV 检测作为 ASC-US 细胞学诊断为宫颈上皮内瘤变二级或更高级别（CIN2+）女性的分流工具的预测价值。
在 2007-08 年期间，来自加泰罗尼亚五个参考实验室的共 611 名新诊断为 ASC-US 的女性接受了高危型 HPV（hrHPV）分流检测，使用高危型 Hybrid Capture 版本 2。使用常规记录链接数据，对女性进行了 3 年的随访，以评估 hrHPV 检测对预测 CIN2+病例的效果。使用逻辑回归分析估计 CIN2+的比值比。
在 611 名诊断为 ASC-US 的女性中，493 名（80.7%）在研究期间至少有一次随访。在研究开始时，48.3%的女性检测到 hrHPV（平均年龄 35.2 岁）。随着年龄的增长，hrHPV 阳性率从 25 岁以下女性的 72.6%下降到 54 岁以上女性的 31.6%（p < 0.01）。在 3 年的随访期结束时，共发现 37 名 CIN2+诊断（18 例 CIN2、16 例 CIN3、2 例癌症和 1 例高度鳞状上皮内病变——HSIL），所有患者在研究开始时均进行了 hrHPV 阳性检测。hrHPV 检测对 CIN2+的敏感性为 97.2%（95%置信区间[CI]为 85.5-99.9），特异性为 68.3%（95%CI 为 63.1-73.2）。与 ASC-US hrHPV 阴性女性相比，ASC-US hrHPV 阳性女性的 CIN2+比值比为 45.3（95%CI：6.2-333.0）。
采用 hrHPV 检测对 ASC-US 进行分流检测对 CIN2+的检测具有较高的敏感性，并且在 3 年随访后具有较高的阴性预测值。该研究结果与当前针对 25-65 岁目标年龄段 ASC-US 女性的分流指南一致。不遵守指南将导致不必要的医疗干预。需要进一步研究以提高 ASC-US 分流的特异性。
