《临床肿瘤学杂志》(Journal of Clinical Oncology) 7月30日在线发表的一份研究报告显示，只需进行1次HPV DNA检测即可预测至少未来18年内女性患宫颈癌的风险，识别出哪些人已经患有浸润性宫颈癌，哪些人的HPV感染未来会导致发病。相比之下，巴氏涂片检查无法预测1~2年后具有重要临床意义的疾病。
美国临床肿瘤学会(ASCO)的Philip E. Castle博士及其同事对来自俄勒冈州波特兰市的由19，512名女性组成的队列进行了分析，所有受试者均在1989~1990年接受了常规细胞学筛查，基线年龄介于16~94岁。研究者采用目前临床上常规使用的商业化诊断性检查手段对受试者的宫颈阴道灌洗液进行了回顾性HPV DNA检测。
受试者接受了大约18年的随访，每年进行1次巴氏涂片检查。在此期间共有199例被确诊为患有浸润性宫颈癌(宫颈上皮内瘤样病变[CIN]3级+)，共发现396例CIN2+患者。基线巴氏涂片阳性对于2年内的宫颈癌具有很强的预测价值，但无法预测该时间点之后的宫颈癌风险。相比之下，HPV DNA检测阳性可持续预测受试者的宫颈癌风险直至研究结束。
举例来说，在入组研究后10~18年期间，与HPV阴性者相比，HPV阳性者被诊断为CIN2+ 和 CIN3+的几率更大，而巴氏涂片阳性者被诊断为CIN2+ 或CIN3+的几率并未高于巴氏涂片阴性者。
同样，基线单次HPV检测阴性与单次巴氏涂片阴性相比，“更能保证受试者在未来18年的随访期内出现CIN2+(1.85% vs. 2.47%)和CIN3+(0.90% vs. 1.27%)的可能性不大。”此外，与巴氏涂片阳性结果相比，HPV阳性结果后出现CIN2+(215例 vs. 136例)和CIN3+(112例vs. 65例)的病例数也更多。在基线HPV DNA检测阳性且随后出现了CIN2+或CIN3+的受试者中，只有一半患者的巴氏涂片检查结果呈阳性。
研究者称，上述结果“进一步支持HPV检测作为30岁及30岁以上女性的常规筛查方法。”此外，其他研究结果表明HPV检测还可能有助于识别出哪些女性存在罹患宫颈原位腺癌和浸润性腺癌的风险，而这两种疾病“单纯通过细胞学筛查是很难发现的”。
Castle博士及其同事指出：“与巴氏涂片检查相比，HPV检测对于CIN3和宫颈癌的预测价值更大，因此可以作为健康女性的宫颈癌筛查手段。而巴氏涂片则可以作为次要的诊断性检查来识别出哪些HPV阳性者近期就有患上浸润性宫颈癌的风险。”
该研究的部分经费由美国国立癌症研究所资助。Castle博士声明与默克、Qiagen和罗氏公司存在利益关系，其同事Attila T. Lorincz博士声明与Qiagen公司存在利益关系。（生物谷Bioon.com）
doi：10.1200/JCO.2011.38.8389
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Clinical Human Papillomavirus Detection Forecasts Cervical Cancer Risk in Women Over 18 Years of Follow-Up
Philip E. Castle， Andrew G. Glass， Brenda B. Rush， David R. Scott， Nicolas Wentzensen， Julia C. Gage， Julie Buckland， Greg Rydzak， Attila T. Lorincz and Sholom Wacholder
Purpose To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction.
Methods Cervicovaginal lavages collected from 19，512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated.
Results A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR， 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up， only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap.
Conclusion HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening， especially in women age 30 years or older.
