Guyot Andrea, Karim Shakir, Kyi May S, Fox John
Department of Microbiology of West Middlesex University Hospital and Quest Diagnostics, Twickenham Rd, Isleworth W7 6AF, UK.
BMC Infect Dis. 2003 Sep 25;3:23. doi: 10.1186/1471-2334-3-23.
As a proportion of high grade cervical intraepithelial neoplasia (CIN2/3) are associated with equivocal cervical smears, which show borderline or mild dyskaryosis, follow up with repeat smears, colposcopy and biopsy is required. Since infection with oncogenic Human Papilloma Virus (HR HPV) has been found to be associated with the development of cervical cancer, HRHPV testing appears to be an alternative.
The present study assesses if HRHPV testing can predict CIN2/3 in women referred for mild dyskaryosis and borderline cytological changes in an health authority with a referral policy to colposcopy after one single mild dyskaryotic Pap smear.
The HPV DNA Hybrid Capture II (Digene/Abbott, Maidenhead) was evaluated on 110 consenting women with mild dyskaryosis and 23 women with persistent borderline changes, who were referred for colposcopy between May and November 2001. A cost comparison between two referral policies was performed.
CIN2/3 was diagnosed histologically in 30 of 133 women (22%) with minor cytological abnormalities. As the Receiver Operator Characteristics plot suggested a cut-off of 3 pg/ml the HRHPV HCII was evaluated at 3 RLU (relative light units) and at the manufacturer's recommendation of 1 RLU. At both cut-offs sensitivity and negative predictive value were high at 97%. Specificity was low at 37% at a cut-off of 1 pg/ml and 46% at a cut-off of 3 RLU. To remain cost neutral in comparison to immediate colposcopy the costs for one HR HPV HC II must not exceed pound 34.37 per test at a cut off of 3 pg/ml.
The negative likelihood ratio (NLR) was of good diagnostic value with 0.089 at 1 RLU and 0.072 at 3 RLU, which reduces the post-test probability for CIN2/3 to 2% in this population. Women with minor cytological disorders can be excluded from colposcopy on a negative HR HPV result.Specificity can be improved by restricting HR HPV testing to women with persistent borderline cytological changes or to women over 30 years.
相当一部分高级别宫颈上皮内瘤变（CIN2/3）与宫颈涂片结果不明确有关，这些涂片显示为边界性或轻度核异质，因此需要通过重复涂片、阴道镜检查和活检进行随访。由于已发现致癌性人乳头瘤病毒（HR HPV）感染与宫颈癌的发生有关，HRHPV检测似乎是一种替代方法。
本研究评估在一个卫生当局，对于因轻度核异质和边界性细胞学改变而转诊进行阴道镜检查的女性，在单次轻度核异质巴氏涂片后遵循转诊政策的情况下，HRHPV检测能否预测CIN2/3。
对2001年5月至11月间转诊进行阴道镜检查的110名同意参与的轻度核异质女性和23名持续性边界性改变女性，评估HPV DNA杂交捕获II（Digene/雅培公司，梅登黑德）。对两种转诊政策进行了成本比较。
133名有轻微细胞学异常的女性中，有30名（22%）经组织学诊断为CIN2/3。由于受试者工作特征曲线表明临界值为3 pg/ml，因此对HRHPV HCII在3个相对光单位（RLU）以及制造商推荐的1个RLU进行评估。在两个临界值下，敏感性和阴性预测值均较高，为97%。在1 pg/ml临界值时特异性较低，为37%，在3个RLU临界值时为46%。为了与立即进行阴道镜检查相比保持成本中性，在3 pg/ml临界值时，每次HR HPV HC II检测的成本不得超过34.37英镑。
阴性似然比（NLR）具有良好的诊断价值，在1个RLU时为0.089，在3个RLU时为0.072，这将该人群中CIN2/3的检测后概率降低至2%。HR HPV检测结果为阴性的有轻微细胞学异常的女性可免于阴道镜检查。通过将HR HPV检测限制在有持续性边界性细胞学改变的女性或30岁以上女性中，可以提高特异性。
