Hughes Sara A, Sun Deqin, Gibson Cheryl, Bellerose Bronya, Rushing Lynda, Chen Hao, Harlow Bernard L, Genest David R, Sheets Ellen E, Crum Christopher P
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Brigham and Women's Hospital, Boston, Mass 02115, USA.
Am J Obstet Gynecol. 2002 Mar;186(3):396-403. doi: 10.1067/mob.2002.121626.
This study related morphologic subtype, human papillomavirus status, and a second cytologic examination to the follow-up biopsy-proven high-grade squamous intraepithelial lesion (HSIL; grade II or III cervical intraepithelial neoplasia) after a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS).
Seven hundred four liquid-based cervical cytology specimens were classified as normal, "ASCUS, favor reactive" (AFR), "ASCUS, not otherwise specified," "ASCUS, favor low-grade squamous intraepithelial lesion," "ASCUS, favor HSIL" (AFHS), low-grade squamous intraepithelial lesion, and HSIL. Human papillomavirus typing used polymerase chain reaction-restriction fragment length polymorphism analysis. A longitudinal review of the cytologic and histologic records of ASCUS cases with > or =1 follow-up test or biopsy ascertained the frequency of a follow-up diagnosis of biopsy-proven HSIL (grade II or III cervical intraepithelial neoplasia).
Three hundred eighty-six cases (208 ASCUS, 68 normal, 86 with low-grade squamous intraepithelial lesions, and 24 with HSIL) were evaluated. High-risk human papillomavirus (HRHPV positive) was lowest with normal cytology (13%), highest with HSIL (71%), and was present in 29.8% of ASCUS cases, ranging from 22.2% (AFR) to 75% (AFHS). Most ASCUS tests (64%) were followed by a negative cytologic or histologic examination. Overall, 3.8% and 11% of ASCUS and HRHPV-positive ASCUS had histologic outcomes of HSIL. AFHS had the highest (25%) and AFR had the lowest (1.1%) proportion of HSIL outcomes. Sensitivity, specificity, and positive predictive values of human papillomavirus testing for biopsy-proven HSIL were 87.5%, 72.5%, and 11.3%, respectively.
HSIL and AFHS are distinguished by the highest frequency of HRHPV types and higher rates of HSIL outcome. The remaining categories of ASCUS are heterogeneous with respect to human papillomavirus type and HSIL risk, and the value of subclassification of these entities is dependent on the practice. A human papillomavirus detection system based on polymerase chain reaction-restriction fragment length polymorphism identifies a smaller percentage of high-risk human papillomaviruses than mixed probe-based methods, probably because of the more precise exclusion of cross-reacting low-risk human papillomavirus. Negative HRHPV findings by either system show a markedly reduced risk of an HSIL outcome. However, the relative advantage of human papillomavirus testing over follow-up cytology will be influenced by the frequency of negative follow-up cytologic examination and sensitivity of liquid-based preparations in a given practice.
本研究将形态学亚型、人乳头瘤病毒状态及第二次细胞学检查与经活检证实为高级别鳞状上皮内病变（HSIL；II或III级宫颈上皮内瘤变）的随访情况相关联，这些HSIL病例最初的细胞学诊断为意义不明确的非典型鳞状细胞（ASCUS）。
704份液基宫颈细胞学标本被分类为正常、“ASCUS，倾向反应性”（AFR）、“ASCUS，未另行说明”、“ASCUS，倾向低级别鳞状上皮内病变”、“ASCUS，倾向HSIL”（AFHS）、低级别鳞状上皮内病变及HSIL。人乳头瘤病毒分型采用聚合酶链反应-限制性片段长度多态性分析。对有≥1次随访检查或活检的ASCUS病例的细胞学和组织学记录进行纵向回顾，以确定经活检证实为HSIL（II或III级宫颈上皮内瘤变）的随访诊断频率。
评估了386例病例（208例ASCUS、68例正常、86例低级别鳞状上皮内病变及24例HSIL）。高危人乳头瘤病毒（HRHPV阳性）在正常细胞学中最低（13%），在HSIL中最高（71%）；在29.8%的ASCUS病例中存在，范围从22.2%（AFR）至75%（AFHS）。大多数ASCUS检查（64%）之后是阴性的细胞学或组织学检查。总体而言，3.8%的ASCUS及11%的HRHPV阳性ASCUS的组织学结果为HSIL。AFHS的HSIL结果比例最高（25%），AFR最低（1.1%）。人乳头瘤病毒检测对经活检证实为HSIL的敏感性、特异性及阳性预测值分别为87.5%、72.5%及11.3%。
HSIL和AFHS的特点是HRHPV类型频率最高且HSIL结果发生率较高。其余ASCUS类别在人乳头瘤病毒类型及HSIL风险方面具有异质性，这些实体的亚分类价值取决于具体实践。基于聚合酶链反应-限制性片段长度多态性的人乳头瘤病毒检测系统识别出的高危人乳头瘤病毒百分比低于基于混合探针的方法，可能是因为更精确地排除了交叉反应的低危人乳头瘤病毒。两种系统的HRHPV阴性结果均显示HSIL结果风险显著降低。然而，人乳头瘤病毒检测相对于随访细胞学的相对优势将受到给定实践中随访细胞学阴性检查频率及液基制片敏感性的影响。
