高危型HPV亚型及亚型组合检测宫颈癌及高级别宫颈上皮内瘤变的比较研究

背景与目的：高危型人乳头状瘤病毒(high risk human papillomavirus，hrHPV)感染对于浸润性宫颈癌(invasive cervical carcinoma，ICC)及其癌前病变的致病性存在亚型及地区差异。本研究通过分析本地区30岁及以上女性宫颈病变患者中HPV亚型分布特点，进一步识别罹患包含ICC的高级别宫颈上皮内瘤变(cervical intraepithelial neoplasia grade 2 or worse，CIN2+)风险更高的亚型，并比较这些高风险亚型及亚型组合检测CIN2+病变的有效性。方法：收集来自复旦大学附属肿瘤医院就诊患者具备组织学随访结果的宫颈标本，行PCR-反向点杂交法(PCR-reverse dot blot，PCR-RDB)HPV基因分型检测，利用Logistic回归模型分析hrHPV亚型与CIN2+病变的风险关系，并构建ROC曲线(receiver operating characteristiccurve，ROC curve)评价不同亚型及亚型组合检测CIN2+病变的准确性。结果：符合研究要求患者413例，含38例CIN1，184例CIN2/3，126例ICC和65例阴性对照人群。HPV16、58、33和18依次为致CIN2+最常见的4种HPV亚型，仅HPV16(P<0.000 1)、58(P=0.002)及33(P=0.015)为罹患CIN2+病变的高风险亚型。联合检测HPV16/18/33/58诊断CIN2+病变的ROC曲线下面积(the area under the ROC curve，AUC)显著高于HPV16/18亚型组合(P=0.006 6)。结论：HPV16/18/33/58亚型组合用于辅助本地区CIN2+病变的检测可能更为有效。

High-risk HPV genotyping for cervical intraepithelial neoplasia grade 2 or worse: A comparison of single types and type combinations

Background and purpose: Risk of invasive cervical carcinoma (ICC) and its precancerous lesions following high risk human papillomavirus (hrHPV) infection may vary according to HPV types and geographic regions. Analyzing HPV-type distribution in cervical samples from local women aged 30 years and older, this study aimed to identify HPV types with higher risk of developing CIN2+, and to compare diagnostic performance for CIN2+ using these types and type combinations. Methods: Cervical samples with histology follow-up from patients of a tertiary cancer center in Shanghai were collected for HPV genotyping by PCR-RDB. The risk associations of HPV types with CIN2+ were estimated by logistic regression analysis, and ROC curves were plotted for diagnostic performance evaluation. Results: A total number of 413 specimens were obtained, including 38 CIN1, 184 CIN2/3, 126 ICC patients and 65 negative control people. The 4 most common HPV types in CIN2+ were HPV16, 58, 33 and 18, in descending order. And only HPV16 (P<0.000 1), 58 (P=0.002), 33 (P=0.015) were significantly associated with CIN2+ lesions.Besides, the area under the ROC curve of the HPV16/18/33/58 test scored statistically higher than the HPV16/18 test did (P=0.006 6). Conclusion: A combined test of HPV16/18/33/58 may offer better performance for detecting CIN2+lesions in our geographic region.