Evans Mark Francis, Adamson Christine Stewart-Crawford, Schned Laura Meredith, St John Timothy Louis, Leiman Gladwyn, Ashikaga Takamaru, Cooper Kumarasen
Department of Pathology, University of Vermont College of Medicine, Burlington, 05405, USA.
Diagn Mol Pathol. 2010 Sep;19(3):144-50. doi: 10.1097/PDM.0b013e3181c1482c.
The demonstration of human papillomavirus (HPV) in 99.7% of cervical carcinoma surgical specimens from around the world required investigations by multiple alternative polymerase chain reaction (PCR) assays. A similar approach may therefore be necessary to best characterize HPV prevalence and genotype distribution among cervical cytology samples. In an earlier study, 752 of 799 (94.1%) abnormal and 82 of 300 (27.3%) normal cytology specimens tested HPV positive after PCR using GP5+/6+primers. This study has reinvestigated the "HPV negative" abnormal samples (20 atypical squamous cells of undetermined significance, 5 low-grade squamous intraepithelial lesion, 14 atypical squamous cells, cannot exclude HSIL, 6 high-grade squamous intraepithelial lesion) and an age-matched cohort of "HPV negative" normal (negative for an intraepithelial lesion or malignancy) samples by PCR using PGMY09/11, FAP59/64, and LCR-E7 primers. PGMY09/11-GP5+/6+ nested PCR was performed on samples that were HPV negative by PGMY09/11 PCR. After the first 3 assays, HPV was detected in 41 of 45 (91.1%) abnormal and in 10 of 47 (21.3%) normal samples (P<0.0001). Eighteen HPV genotypes were detected and in some samples the genotype that was identified differed between the tests. The nondetection of common HPV genotypes (eg, HPVs 6, 11, 16, and 18) was notable. High-grade histopathology was found for 2 patients with HPV52-positive cytopathology. Combined with our earlier study, HPV (40 different genotypes) is shown in 99.5% of abnormal samples (99.8% inclusive of the nested PCR data). These findings show that HPV genotype and prevalence estimates are dependent on the method(s) of detection and indicate that suboptimal analytical sensitivity for one or more of the less common high-risk HPV genotypes could lead to impaired clinical sensitivity. HPV may be causal in almost every instance of abnormal cervical cytology; however, passenger HPV that is incidental to an abnormality may also have been detected.
在来自世界各地的99.7%的宫颈癌手术标本中检测到人乳头瘤病毒（HPV），这需要通过多种替代聚合酶链反应（PCR）检测方法进行研究。因此，对于宫颈细胞学样本中HPV的流行率和基因型分布进行最佳特征描述，可能也需要类似的方法。在一项早期研究中，使用GP5+/6+引物进行PCR检测后，799份异常细胞学标本中的752份（94.1%）以及300份正常细胞学标本中的82份（27.3%）HPV呈阳性。本研究重新检测了“HPV阴性”的异常样本（20份意义不明确的非典型鳞状细胞、5份低级别鳞状上皮内病变、14份非典型鳞状细胞，不能排除高级别鳞状上皮内病变、6份高级别鳞状上皮内病变）以及一组年龄匹配的“HPV阴性”正常样本（上皮内病变或恶性肿瘤阴性），采用PGMY09/11、FAP59/64和LCR-E7引物进行PCR检测。对PGMY09/11 PCR检测为HPV阴性的样本进行PGMY09/11-GP5+/6+巢式PCR检测。在前3次检测后，45份异常样本中的41份（91.1%）以及47份正常样本中的10份（21.3%）检测到HPV（P<0.0001）。检测到18种HPV基因型，在一些样本中，不同检测方法鉴定出的基因型有所不同。未检测到常见的HPV基因型（如HPV 6、11、16和18）值得注意。2例HPV52阳性细胞病理学患者发现高级别组织病理学改变。结合我们早期的研究，99.5%的异常样本中显示有HPV（40种不同基因型）（包括巢式PCR数据在内为99.8%）。这些发现表明，HPV基因型和流行率估计取决于检测方法，并且表明对于一种或多种较不常见的高危HPV基因型而言，分析灵敏度欠佳可能会导致临床灵敏度受损。HPV可能在几乎每一例宫颈细胞学异常中都起作用；然而，也可能检测到了与异常情况偶然相关的过客型HPV。
