Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Jul;20(7):1398-409. doi: 10.1158/1055-9965.EPI-11-0206. Epub 2011 May 20.
Human papillomavirus (HPV) DNA testing is more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 3 and cancer (≥CIN3). Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare.
Beginning in 1989-1990, ~20,000 women in a prepaid health maintenance organization (median age = 34) were followed passively by recommended annual cytology. We tested archived cervicovaginal lavage specimens collected at enrollment, primarily by MY09-MY11 PCR-based methods, for carcinogenic HPV types. We calculated positive and negative predictive values for the entire study period, and Kaplan-Meier estimates of cumulative probability for ≥CIN3, up to 18 years of follow-up.
We observed 47 cases of invasive cervical cancer during the study period, and 156 cases of CIN3. Predictive values and Kaplan-Meier analyses yielded the same conclusions. In women 30 and older, the reassurance against ≥CIN3 following a single negative HPV test was long-lasting (cumulative probability = 0.7% during follow-up). In this age group, a single HPV test (positive vs. negative, hazard ratio of 8.5, 95% CI = 4.8-15.1) provided greater long-term risk stratification than a single cytologic result (abnormal vs. normal, HR = 2.9, 95% CI = 1.2-6.6). The risk for ≥CIN3 was higher for HPV16 than for the average of the other carcinogenic types (hazard ratio = 2.7).
The data from this cohort study show the long-term predictive value of HPV testing, particularly in women ≥30, and a possible role for distinguishing particularly carcinogenic types like HPV16.
人乳头瘤病毒（HPV）DNA 检测比细胞学检查更敏感，可用于检测宫颈上皮内瘤变 3 级及以上病变（≥CIN3）和癌症。建议对年龄≥30 岁的女性进行 HPV 检测联合细胞学检查。然而，HPV 检测的长期前瞻性研究较为罕见。
1989-1990 年，我们对一个预付款健康维护组织中的约 20000 名女性进行了被动随访，她们接受了推荐的年度细胞学检查。我们主要采用 MY09-MY11 基于聚合酶链反应（PCR）的方法检测存档的宫颈阴道灌洗液标本，以检测致癌 HPV 型。我们计算了整个研究期间 HPV 检测的阳性和阴性预测值，并通过 Kaplan-Meier 估计了≥CIN3 的累积概率，随访时间长达 18 年。
在研究期间，我们观察到 47 例浸润性宫颈癌和 156 例 CIN3 病例。预测值和 Kaplan-Meier 分析得出了相同的结论。在年龄≥30 岁的女性中，单次 HPV 检测阴性可长期排除≥CIN3（随访期间累积概率为 0.7%）。在这个年龄组中，单次 HPV 检测（阳性与阴性相比，危险比为 8.5，95%可信区间为 4.8-15.1）比单次细胞学检查（异常与正常相比，危险比为 2.9，95%可信区间为 1.2-6.6）提供了更好的长期风险分层。HPV16 的风险高于其他致癌类型的平均水平（危险比为 2.7）。
该队列研究的数据显示了 HPV 检测的长期预测价值，尤其是在年龄≥30 岁的女性中，并且可能有助于区分 HPV16 等特别致癌类型。
