van der Marel Jacolien, Berkhof Johannes, Ordi Jaume, Torné Aureli, Del Pino Marta, van Baars Romy, Schiffman Mark, Wentzensen Nicolas, Jenkins David, Quint Wim G V
*DDL Diagnostic Laboratory, Rijswijk †Department of Epidemiology and Biostatistics, VU Medical Center, Amsterdam, The Netherlands ‡Department of Pathology, CRESIB (Centre de Recerca en Salut Internacional de Barcelona) §Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clínic, Spain ∥Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Am J Surg Pathol. 2015 Apr;39(4):496-504. doi: 10.1097/PAS.0000000000000342.
Human papillomavirus (HPV) is found in most women with high-grade cervical intraepithelial neoplasia (CIN) 2/3 in cervical cytology and biopsies. Multiple high-risk HPV (hrHPV) genotypes are present in 15% to 50% of cytology samples. We have shown by laser-capture microscopy (LCM)-polymerase chain reaction (PCR) that each lesion is associated with a single hrHPV type. Attribution of hrHPV types to CIN2/3 is important to understand the oncogenic role of different types and the limitations of cytologic typing. We studied hrHPV genotypes in 257 women with histologic CIN2/3 referred on the basis of abnormal cytology. HPV typing was done on cytology and CIN2/3 biopsies. If the whole-tissue section of the biopsy was positive for multiple hrHPV types, LCM-PCR was performed. We found 181 (70%) single and 71 (28%) multiple hrHPV infections in cytology, with 5 (2%) cases HPV-positive only on whole-tissue section PCR. Of cases with multiple cytologic hrHPV infections, 47/71 (66%) showed a single type in CIN2/3 lesions. In total, in 232 of 257 (90%) women with CIN2/3, a single hrHPV type caused CIN2/3. One was nonattributable on the LCM level. The remaining 24 women had 2 or more contiguous or separated lesions, each associated with a single hrHPV infection. The probability of HPV16 being present in CIN2/3, if detected in cytology, was 0.96 (95% confidence interval=0.90-0.98). LCM-PCR confirms that only 9% of histologic CIN2/3 is associated with multiple hrHPV types, much less than cytology would indicate, and each lesion was associated with a single hrHPV infection.
在宫颈细胞学检查和活检中，大多数高级别宫颈上皮内瘤变（CIN）2/3的女性体内都能检测到人乳头瘤病毒（HPV）。15%至50%的细胞学样本中存在多种高危型HPV（hrHPV）基因型。我们通过激光捕获显微镜（LCM）-聚合酶链反应（PCR）证实，每个病变都与单一的hrHPV类型相关。确定CIN2/3的hrHPV类型对于理解不同类型的致癌作用以及细胞学分型的局限性至关重要。我们研究了257名因细胞学异常而转诊的组织学诊断为CIN2/3的女性的hrHPV基因型。对细胞学样本和CIN2/3活检组织进行HPV分型。如果活检组织的整个切片对多种hrHPV类型呈阳性，则进行LCM-PCR检测。我们在细胞学检查中发现181例（70%）为单一hrHPV感染，71例（28%）为多种hrHPV感染，5例（2%）仅在组织全切片PCR中呈HPV阳性。在细胞学检查为多种hrHPV感染的病例中，47/71（66%）在CIN2/3病变中显示为单一类型。总体而言，257例CIN2/3女性中有232例（90%）由单一的hrHPV类型导致CIN2/3。1例在LCM水平上无法确定类型。其余24名女性有2个或更多相邻或不相邻的病变，每个病变都与单一的hrHPV感染相关。如果在细胞学检查中检测到HPV16，则其在CIN2/3中出现的概率为0.96（95%置信区间=0.90-0.98）。LCM-PCR证实，只有9%的组织学CIN2/3与多种hrHPV类型相关，远低于细胞学检查所提示的比例，且每个病变都与单一的hrHPV感染相关。
