Pirog Edyta C, Lloveras Belen, Molijn Anco, Tous Sara, Guimerà Núria, Alejo Maria, Clavero Omar, Klaustermeier Joellen, Jenkins David, Quint Wim Gv, Xavier Bosch Francesc, Alemany Laia, de Sanjosé Silvia
Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA.
Department of Pathology, Hospital del Mar, Barcelona, Spain.
Mod Pathol. 2014 Dec;27(12):1559-67. doi: 10.1038/modpathol.2014.55. Epub 2014 Apr 25.
The goal of our study was to provide comprehensive data on the worldwide human papillomavirus (HPV) genotype distribution in patients with invasive cervical adenocarcinoma in correlation with histologic tumor subtypes, geographical location, patients' age, and duration of sample storage. Paraffin-embedded samples of 760 cervical adenocarcinoma cases were collected worldwide. A three-level pathology review of cases was performed to obtain consensus histologic diagnoses and 682 cases were determined to be eligible for further analysis. HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA(25) system (version 1). Classic cervical adenocarcinoma accounted for 83.1% of cases, while rare histological variants accounted for a few percent of cases individually. HPV positivity varied significantly between the different histologic tumor subtypes. Classic cervical adenocarcinoma showed high HPV positivity (71.8%), while other adenocarcinoma types had significantly lower HPV prevalence (endometrioid 27.3%, serous 25%, clear cell 20%, not otherwise specified 13.9%, and minimal deviation 8.3%). In all, 91.8% of HPV-positive tumors showed the presence of a single viral type and in 7% of cases multiple viral types were detected. Three HPV genotypes, HPV 16, 18, and 45, dominated in all adenocarcinomas and together accounted for 94.1% of HPV-positive tumors. HPV16 was the most common and found in 50.9% of HPV-positive cases, followed by HPV18 (31.6%) and HPV45 (11.6%). HPV prevalence varied depending on geographical region, patient age, and sample storage time. Tumors from older patients and tumor samples with longer storage time showed lower HPV prevalence. Our results indicate that HPV vaccines may prevent up to 82.5% (HPV16/18) and up to 95.3% (9-valent vaccine) of HPV-positive cervical adenocarcinomas, mostly the classic type. HPV testing and vaccination will not provide full coverage for a very small subset of classical adenocarcinomas and most of the rare tumor variants such as clear cell, serous, endometrioid, and minimal deviation.
我们研究的目的是提供关于全球浸润性宫颈腺癌患者人乳头瘤病毒(HPV)基因型分布的全面数据,这些数据与组织学肿瘤亚型、地理位置、患者年龄以及样本储存时长相关。我们在全球范围内收集了760例宫颈腺癌病例的石蜡包埋样本。对病例进行了三级病理学评估以获得一致的组织学诊断,最终确定682例病例符合进一步分析的条件。使用SPF - 10/DEIA/LiPA(25)系统(版本1)进行HPV DNA检测和基因分型。经典宫颈腺癌占病例的83.1%,而罕见组织学变体各自占病例的百分之几。HPV阳性率在不同组织学肿瘤亚型之间差异显著。经典宫颈腺癌显示出较高的HPV阳性率(71.8%),而其他腺癌类型的HPV患病率则显著较低(子宫内膜样腺癌27.3%,浆液性癌25%,透明细胞癌20%,未另行分类13.9%,微小偏离型8.3%)。总体而言,91.8%的HPV阳性肿瘤显示存在单一病毒类型,7%的病例检测到多种病毒类型。三种HPV基因型,即HPV 16、18和45,在所有腺癌中占主导地位,共占HPV阳性肿瘤的94.1%。HPV16最为常见,在50.9%的HPV阳性病例中被发现,其次是HPV18(31.6%)和HPV45(11.6%)。HPV患病率因地理区域、患者年龄和样本储存时间而异。老年患者的肿瘤以及储存时间较长的肿瘤样本显示出较低的HPV患病率。我们的结果表明,HPV疫苗可能预防高达82.5%(HPV16/18)以及高达95.3%(九价疫苗)的HPV阳性宫颈腺癌,主要是经典类型。HPV检测和疫苗接种无法为极小部分的经典腺癌以及大多数罕见肿瘤变体(如透明细胞癌、浆液性癌、子宫内膜样腺癌和微小偏离型)提供全面覆盖。