Reid R, Crum C P, Herschman B R, Fu Y S, Braun L, Shah K V, Agronow S J, Stanhope C R
Cancer. 1984 Feb 15;53(4):943-53. doi: 10.1002/1097-0142(19840215)53:4<943::aid-cncr2820530421>3.0.co;2-x.
Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.
人乳头瘤病毒（HPV）感染目前被广泛认为是宫颈癌的一个重要病因。本研究旨在阐明在将亚临床乳头瘤病毒感染（SPI）与宫颈上皮内瘤变（CIN）联系起来的生物学谱内的形态学关系。两位病理学家使用一种半客观评分方案分析了72份阴道镜活检标本，该方案对24种不同的组织学标准进行评分。对每个单独的标准进行了重复性检查，并与乳头瘤病毒感染的客观指标（免疫过氧化物酶染色）或癌前病变（显微分光光度法）进行了验证。然后将这些单独的标准合并为良性疣状改变、假定的病毒异型性、异常细胞表型和组织成熟紊乱的组织学指数。乳头瘤病毒感染的组织学表达随着癌前病变程度的增加而降低。将异常细胞表型指数与组织成熟紊乱指数绘制成图，得到一个线性图，其中病例聚为四个诊断组。乳头瘤病毒感染的组织学指数与基因型畸变显示出显著的曲线相关性，良性疣状改变在CIN 1范围内最大，假定的病毒异型性在CIN 2范围内最大。随着诊断恶化，核DNA含量的紊乱也增加；二倍体在SPI中最常见（67%），多倍体在CIN 1中（59%），非整倍体在CIN 2中（65%）和CIN 3中（82%）。相反，衣壳抗原产生率从SPI中的36%降至CIN 3中的9%。三个非整倍体上皮免疫过氧化物酶呈阳性。病毒晚期表达与核畸变之间的这些反比关系符合病毒致癌的实验模型。诊断组之间的逐渐过渡和形态学重叠支持了SPI和CIN是单一疾病谱的假设，其中差异是程度上的而非种类上的。
