Nygård Mari, Røysland Kjetil, Campbell Suzanne, Dillner Joakim
Department of Research, Cancer Registry of Norway, Oslo, Norway.
BMJ Open. 2014 Jan 8;4(1):e003460. doi: 10.1136/bmjopen-2013-003460.
To compare the short-term and long-term effectiveness of human papillomavirus (HPV) tests in Norwegian Cervical Cancer Screening Programme (NCCSP).
Nationwide register-based prospective follow-up study.
In 2005, the NCCSP implemented HPV testing in follow-up of unsatisfactory, atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) cytology.
19 065 women with repeat cytology and HPV test after unsatisfactory ASC-US or LSIL screening result in 2005-2009.
Through individual registry linkages we observed how women were treated in the regular medical care.
We estimated cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in 6 months and 3 years after repeat cytology and HPV test. Patients diagnosed with CIN2+ in 6 months and 3 years were assessed for initial HPV positivity.
5392 had ASC-US/LSIL and 13 673 had normal/unsatisfactory repeat cytology; for HPV detection 4715 used AMPLICOR HPV Test (Roche Diagnostics, Basel, Switzerland), 9162 Hybrid Capture 2 (HC2) High-Risk HPV DNA Test (QIAGEN, Gaithersburg, Maryland, USA) and 5188 PreTect HPV-Proofer (NorChip, Klokkarstua, Norway). Among those with ASC-US/LSIL repeat cytology, 3-year risk of CIN2+ was 15-fold in Amplicor/HC2-positives compared with Amplicor/HC2-negatives and sevenfold in Proofer-positives compared with Proofer-negatives; a 3-year risk of CIN2+ was 2.1% (95% CI 0.7% to 3.4%) in Amplicor-negatives and 7.2% (95% CI 5.4% to 8.9%) in Proofer-negatives. Close to 100% of patients with CIN2+ diagnosed within 6 months tested positive to HPV (all methods). Considering all patients diagnosed with CIN2+ in 3-year follow-up, 97% were initially positive in the Amplicor group and more than 94% in the HC2 group, compared with less than 80% in the Proofer group.
While the long-term evaluation of new screening routines showed a good overall performance of triage-HPV DNA testing, the management of HPV-negative women with persistent ASC-US/LSIL was suboptimal.
比较人乳头瘤病毒（HPV）检测在挪威宫颈癌筛查计划（NCCSP）中的短期和长期效果。
基于全国登记的前瞻性随访研究。
2005年，NCCSP在对不满意的意义不明确的非典型鳞状细胞（ASC-US）和低级别鳞状上皮内病变（LSIL）细胞学检查进行随访时实施了HPV检测。
2005年至2009年间，19065名女性在ASC-US或LSIL筛查结果不满意后进行了重复细胞学检查和HPV检测。
通过个人登记链接，我们观察了女性在常规医疗护理中的治疗情况。
我们估计了重复细胞学检查和HPV检测后6个月及3年时宫颈上皮内瘤变2级或更高级别（CIN2+）的累积发病率。对在6个月和3年时被诊断为CIN2+的患者评估其初始HPV阳性情况。
5392人有ASC-US/LSIL，13673人重复细胞学检查结果正常/不满意；对于HPV检测，4715人使用了AMPLICOR HPV检测（罗氏诊断公司，瑞士巴塞尔），9162人使用了杂交捕获2（HC2）高危型HPV DNA检测（QIAGEN公司，美国马里兰州盖瑟斯堡），5188人使用了PreTect HPV-Proofer（挪威NorChip公司，克洛卡斯图阿）。在ASC-US/LSIL重复细胞学检查的人群中，与AMPLICOR/HC2阴性者相比，AMPLICOR/HC2阳性者CIN2+的3年风险高15倍，与Proofer阴性者相比，Proofer阳性者CIN2+的3年风险高7倍；AMPLICOR阴性者CIN2+的3年风险为2.1%（95%CI 0.7%至3. .4%），Proofer阴性者为7.2%（95%CI 5.4%至8.9%）。在6个月内被诊断为CIN2+的患者中，接近100%的人HPV检测呈阳性（所有方法）。在3年随访中，考虑所有被诊断为CIN2+的患者，AMPLICOR组中97%的人初始呈阳性，HC2组中超过94%的人初始呈阳性, 而Proofer组中不到80%的人初始呈阳性。
虽然对新筛查程序的长期评估显示分流HPV DNA检测的总体表现良好，但对持续存在ASC-US/LSIL的HPV阴性女性的管理并不理想。
