Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, Bethesda, MD 20892, USA.
J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S56-63. doi: 10.1097/LGT.0b013e318285437b.
Current US guidelines for cotesting recommend that the large numbers of women who test Pap-negative, but human papillomavirus (HPV)-positive, return in 1 year, and those who remain HPV-positive or have low-grade squamous intraepithelial lesion (LSIL) or worse Pap results be referred for colposcopy. However, the performance of these guidelines in routine clinical practice has not been evaluated.
We estimated cumulative 5-year risks of cervical intraepithelial neoplasia grade 3 or worse (CIN 3+) among 32,374 women aged 30 to 64 years with HPV-positive/Pap-negative cotest results at Kaiser Permanente Northern California during 2003 to 2010.
The 5-year CIN 3+ risk after an HPV-positive/Pap-negative cotest result, which was found in 3.6% of women, was 4.5% (95% confidence interval [CI] = 4.2%-4.8%). The 5-year cancer risk was 0.34% (95% CI = 0.26%-0.45%), and half of the cases were adenocarcinoma. Overall, 48% of the women remained HPV-positive on return (median = 418 days after baseline), a percentage that varied little over ages 30 to 64 years. At the return after a baseline HPV-positive/Pap-negative result, almost every repeat cotest result predicted greater subsequent 5-year CIN 3+ risk than the same cotest result had at baseline (HPV-positive/LSIL, 9.2% vs 6.1%, p = .01; HPV-positive/atypical squamous cells of undetermined significance [ASC-US], 7.9% vs 6.8%, p = .2; HPV-positive/Pap-negative, 7.4% vs 4.5%, p < .0001; HPV-negative/LSIL,1.7% vs 2.0%, p = .8; HPV-negative/ASC-US, 2.9% vs 0.43%, p = .0005; HPV-negative/Pap-negative, 0.93% vs 0.08%, p < .0001).
Using the principle of "equal management of equal risks," women testing HPV-positive/Pap-negative had a subsequent CIN 3+ risk consistent with risk thresholds for a 1-year return. However, on returning in approximately 1 year, about one-half of women will be referred for colposcopy because of continued HPV positivity or Pap abnormality. Clinicians should keep in mind that cotest results at the return after a baseline HPV-positive/Pap-negative finding are riskier than the same baseline cotest results in the general population, supporting intensified clinical management at return testing.
目前美国的联合检测指南建议大量巴氏涂片阴性但人乳头瘤病毒（HPV）阳性的女性在 1 年内复诊，而那些 HPV 持续阳性或出现低级别鳞状上皮内病变（LSIL）或更高级别巴氏涂片结果的患者应转诊行阴道镜检查。然而，这些指南在常规临床实践中的应用效果尚未得到评估。
我们在 2003 年至 2010 年期间，对 Kaiser Permanente Northern California 年龄在 30 至 64 岁之间的 32374 名 HPV 阳性/巴氏涂片阴性联合检测结果阳性的女性进行了研究，估计了其 5 年内发生宫颈上皮内瘤变 3 级及以上（CIN3+）的累积风险。
5 年内，在 3.6%的女性中发现 HPV 阳性/巴氏涂片阴性联合检测结果的 CIN3+风险为 4.5%（95%置信区间为 4.2%-4.8%）。癌症的 5 年风险为 0.34%（95%置信区间为 0.26%-0.45%），且半数病例为腺癌。总体而言，48%的女性在复诊时仍为 HPV 阳性（中位随访时间为基线后 418 天），且这一比例在 30 至 64 岁的年龄范围内变化不大。在基线 HPV 阳性/巴氏涂片阴性结果的复诊时，几乎每一次重复联合检测结果预测的后续 5 年 CIN3+风险都高于同一联合检测结果的基线风险（HPV 阳性/LSIL，9.2%比 6.1%，p=0.01；HPV 阳性/非典型意义不明确的鳞状细胞（ASC-US），7.9%比 6.8%，p=0.2；HPV 阳性/巴氏涂片阴性，7.4%比 4.5%，p<0.0001；HPV 阴性/LSIL，1.7%比 2.0%，p=0.8；HPV 阴性/ASC-US，2.9%比 0.43%，p=0.0005；HPV 阴性/巴氏涂片阴性，0.93%比 0.08%，p<0.0001）。
根据“相同风险相同管理”的原则，HPV 阳性/巴氏涂片阴性的女性发生 CIN3+的风险与 1 年复诊的风险阈值一致。然而，大约 1 年后复诊时，约有一半的女性将因 HPV 持续阳性或巴氏涂片异常而被转诊行阴道镜检查。临床医生应牢记，与一般人群相比，在基线 HPV 阳性/巴氏涂片阴性的基础上，复诊时的联合检测结果风险更高，这支持在复诊时加强临床管理。
