BACKGROUND Human Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. However, additional efficient strategies should be developed to improve the specificity of these tests. METHODS This study aimed to evaluate the clinical value of HPV DNA load in improving the diagnosis and prognosis of cervical lesions by p16/Ki-67 testing. Histological samples were collected from 350 women with HR-HPV genotyping and analyzed by qRT-PCR. Immunohistochemical staining was used to assess p16 and Ki-67 expression and clinical performance characteristics were calculated. RESULTS Of the cases, 271 had detectable HR-HPV infection, in which HPV-16 was most prevalent (52.0%), followed by HPV-58 (22.5%). P16/Ki-67-positivity increased with histological severity but not for HR-HPV infection. Amongst the 13 HR-HPV genotypes, only HPV-16 (P = 0.016) and HPV-58 (P = 0.004) viral loads significantly correlated with lesion severity. The P16/Ki-67/HPV DNA load co-test indicated an increased sensitivity for the detection of cervical intraepithelial neoplasia (CIN) lesions compared to p16/Ki-67 staining in HPV-16 and/or 58 positive cases. Viral load did not improve the sensitivity of p16/Ki-67 co-test in non-HPV-16 or 58 positive cases. The clinical performance of the p16/Ki-67/HPV DNA load co-test was limited for the prediction of the outcome of CIN1 lesions. However, amongst the 12 HPV-16 and/or 58 positive CIN2 cases in which return visit results were obtained, the behavior of the lesions could be predicted, with a sensitivity, specificity, positive prediction rate (PPV), and negative prediction rate (NPV) of 0.667, 1, 1 and 0.5, respectively. CONCLUSION Combination of the assessment of HPV DNA load with the intensity of p16 and Ki-67 staining could increase the sensitivity of CIN lesion diagnosis and predict the outcome of CIN2 in patients with a HPV-16 and/or 58 infection.

中文翻译：

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将HPV DNA负载量与p16 / Ki-67染色相结合，以检测宫颈癌前病变并预测CIN1-2病变的进展。

背景技术人乳头瘤病毒（HPV）DNA测试高度敏感，可以对患有轻度病变的妇女进行分类，从而改善宫颈病变的预后和诊断。但是，应开发其他有效策略来提高这些测试的特异性。方法本研究旨在通过p16 / Ki-67检测评估HPV DNA负载量在改善宫颈病变的诊断和预后中的临床价值。从350名HR-HPV基因分型的女性中收集组织学样本，并通过qRT-PCR进行分析。免疫组织化学染色用于评估p16和Ki-67的表达，并计算临床表现特征。结果在这些病例中，有271例可检测到HR-HPV感染，其中HPV-16最为流行（52.0％），其次是HPV-58（22.5％）。P16 / Ki-67阳性随组织学严重程度而增加，但对于HR-HPV感染则不增加。在13种HR-HPV基因型中，只有HPV-16（P = 0.016）和HPV-58（P = 0.004）病毒载量与病变严重程度显着相关。与HPV-16和/或58例阳性病例中的p16 / Ki-67染色相比，P16 / Ki-67 / HPV DNA负载共同测试表明检测宫颈上皮内瘤样病变（CIN）的敏感性更高。在非HPV-16或58例阳性病例中，病毒载量并未提高p16 / Ki-67共同测试的敏感性。p16 / Ki-67 / HPV DNA负载共同测试的临床表现对于CIN1病变预后的预测是有限的。但是，在获得回诊结果的12例HPV-16和/或58例阳性CIN2病例中，可以预测病变的行为，并具有敏感性，特异性，正预测率（PPV）和负预测率（NPV）分别为0.667、1、1和0.5。结论将HPV DNA负荷评估与p16和Ki-67染色强度相结合可以提高HPV-16和/或58感染患者CIN病变诊断的敏感性并预测CIN2的结果。