Pirog Edyta C, Erroll Maria, Harigopal Malini, Centeno Barbara A
Department of Pathology, The Papanicolaou Laboratory, Weill Medical College of Cornell University, New York, NY 10021, USA.
Arch Pathol Lab Med. 2004 May;128(5):527-32. doi: 10.5858/2004-128-527-COHPDP.
The new Bethesda System 2001 (TBS 2001) minimized the subclassification of atypical squamous cells of undetermined significance (ASCUS).
The primary goal of this study was to determine the impact of the new subclassification on the accuracy of Papanicolaou (Pap) test diagnosis by examining the prevalence of human papillomavirus (HPV) DNA in different ASCUS subcategories, as defined by the new TBS 2001 versus the original TBS 1991. The second goal was to identify specific morphologic features of atypical squamous cells that are more frequently associated with HPV detection.
Consecutive cases of ThinPrep Pap tests were retrospectively reviewed by a panel of pathologists to obtain consensus diagnoses. The study group consisted of ASCUS cases; the positive control group consisted of low- and high-grade squamous intraepithelial lesions (LSILs and HSILs, respectively); and the negative control group consisted of cases "negative for intraepithelial lesion or malignancy." All ASCUS cases were subclassified according to TBS 1991 into the following categories: favor reactive (ASCUS-R), favor LSIL (ASCUS-L), favor HSIL (ASCUS-H), and not otherwise specified (ASCUS-NOS). In a separate review, ASCUS cases were subclassified according to TBS 2001 into the following categories: atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). Furthermore, morphologic ASCUS subtypes were recorded (atypical mature, immature, parakeratotic, and atrophic cells); in addition, individual morphologic features of atypical cells were recorded. Broad- spectrum HPV DNA amplification and genotyping was performed using short PCR fragment (SPF 10) polymerase chain reaction/Line Probe assays.
In cases classified according to TBS 1991, HPV was detected in 32% of negative, 49% of ASCUS, and 93% of LSIL/HSIL cases. On the second review, using the diagnostic categories of TBS 2001, which eliminated the ASCUS-;R category, the number of ASCUS cases decreased by 45%. The prevalence of HPV DNA in ASCUS cases downgraded to the negative category was 38%, which was not significantly different from HPV prevalence in negative cases as diagnosed under TBS 1991. Furthermore, HPV was detected in 56% of ASC-US and 71% of ASC-H cases. The prevalence of HPV in different morphologic subtypes of ASCUS was not significantly different, and none of the 8 individual morphologic features of atypical cells were more frequently associated with HPV detection.
Elimination of the ASCUS-R category in TBS 2001 resulted in a significant decrease in the number of ASCUS diagnoses. Downgraded cases had a relatively low prevalence of HPV DNA. It is expected that TBS 2001 will increase specificity of the Pap test without compromising its sensitivity.
2001年新的贝塞斯达系统（TBS 2001）减少了意义不明确的非典型鳞状细胞（ASCUS）的亚分类。
本研究的主要目的是通过检查不同ASCUS亚分类中人类乳头瘤病毒（HPV）DNA的流行情况，来确定新亚分类对巴氏（Pap）试验诊断准确性的影响，这些亚分类由新的TBS 2001与原来的TBS 1991定义。第二个目的是识别与HPV检测更常相关的非典型鳞状细胞的特定形态学特征。
一组病理学家对液基薄层Pap试验的连续病例进行回顾性检查以获得一致诊断。研究组由ASCUS病例组成；阳性对照组分别由低级别和高级别鳞状上皮内病变（LSIL和HSIL）组成；阴性对照组由“上皮内病变或恶性肿瘤阴性”病例组成。所有ASCUS病例根据TBS 1991被亚分类为以下类别：倾向反应性（ASCUS-R）、倾向LSIL（ASCUS-L）、倾向HSIL（ASCUS-H）和未另行指定（ASCUS-NOS）。在另一次检查中，ASCUS病例根据TBS 2001被亚分类为以下类别：意义不明确的非典型鳞状细胞（ASC-US）和非典型鳞状细胞，不能排除高级别鳞状上皮内病变（ASC-H）。此外，记录了ASCUS的形态学亚型（非典型成熟、不成熟、不全角化和萎缩细胞）；另外，记录了非典型细胞的个体形态学特征。使用短PCR片段（SPF 10）聚合酶链反应/线性探针分析法进行广谱HPV DNA扩增和基因分型。
在根据TBS 1991分类的病例中，HPV在32%的阴性病例、49%的ASCUS病例和93%的LSIL/HSIL病例中被检测到。在第二次检查中，使用消除了ASCUS-R类别的TBS 2001诊断类别，ASCUS病例数量减少了45%。降级为阴性类别的ASCUS病例中HPV DNA的流行率为38%，与TBS 1991诊断的阴性病例中HPV流行率无显著差异。此外，HPV在56%的ASC-US病例和71%的ASC-H病例中被检测到。ASCUS不同形态学亚型中HPV的流行率无显著差异，非典型细胞的8个个体形态学特征中没有一个与HPV检测更常相关。
TBS 2001中ASCUS-R类别的消除导致ASCUS诊断数量显著减少。降级病例中HPV DNA的流行率相对较低。预计TBS 2001将提高Pap试验的特异性而不损害其敏感性。
