Informed Cytology for Triaging HPV-Positive Women: Substudy Nested in the NTCC Randomized Controlled Trial
Informed Cytology for Triaging HPV-Positive Women: Substudy Nested in the NTCC Randomized Controlled Trial
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DOI：
10.1093/jnci/dju423
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发表时间：
2015-02-01
影响因子：
10.3
通讯作者：
Ronco, Guglielmo
中科院分区：
文献类型：
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作者：
Bergeron, Christine;Giorgi-Rossi, Paolo;Ronco, Guglielmo
背景：基于人乳头瘤病毒（HPV）的筛查需要分诊。在大多数随机对照试验（RCT）的HPV检测与细胞学分诊，细胞学解释一直盲目HPV status.Methods：妇女年龄25至60岁的新技术在宫颈癌（NTCC）RCT比较HPV检测与细胞学被称为阴道镜检查，如果HPV阳性，如果没有宫颈上皮内瘤样病变（CIN）被检测到，随访，直到HPV阴性。在第一次阴道镜检查时采集的细胞学切片由外部实验室检索和独立解释，该实验室仅知道患者的HPV阳性。对于确定为不确定意义的非典型鳞状细胞（ASCUS）或更严重的女性，通过HPV状态告知细胞学检查，计算组织学证实的CIN 2+的敏感性、特异性和阳性（PPV）和阴性（NPV）预测值。所有统计检验均为双侧检验。在HPV阳性妇女中，知情细胞学检查对CIN 2+的横断面敏感性、特异性、PPV和1-NPV为85.6%（95%置信区间[CI] = 76.6至92.1）、65.9%（95% CI = 63.1至68.6）、16.2%（95% CI = 13.0至19.8）和1.7（95% CI = 0.9至2.8）。细胞学检查也与新诊断的CIN 2+和CIN 3+的后续风险相关。通过参考阴道镜检查并仅随访HPV状态告知细胞学检查结果大于或等于ASCUS的HPV阳性女性，获得的CIN 2+与盲法细胞学检查的横断面相对灵敏度为1.58（95%CI = 1.22 - 2.01），而相应的阴道镜检查的相对参考值为0.95结论：HPV阳性的细胞学检查比盲法细胞学检查更敏感，并且可以在HPV阳性，细胞学阴性的妇女重新检测之前允许更长的间隔。
Background: Human papillomavirus (HPV)-based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status.Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients' HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status-informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided.Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status-informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04).Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.