Toki T, Kurman R J, Park J S, Kessis T, Daniel R W, Shah K V
Department of Gynecology and Obstetrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Int J Gynecol Pathol. 1991;10(2):107-25. doi: 10.1097/00004347-199104000-00001.
A clinical, pathologic, and molecular virologic analysis of 30 cases of invasive squamous cell carcinoma of the vulva was undertaken to investigate the relationship of human papillomavirus (HPV) to this neoplasm. The presence of the virus was detected by the polymerase chain reaction and localized in the tumor and in the adjacent epithelium by in situ hybridization of paraffin sections of vulvectomy specimens. Specimens were examined for nucleic acid sequences of HPVs 6, 11, 16, and 18 were detected by in situ hybridization utilizing 35S-labeled antisense RNA probes and by polymerase chain reaction using HPV type-specific primers for a segment of the E6 gene followed by Southern hybridization of the amplified products. The cases were classified as typical squamous cell carcinoma, basaloid carcinoma, and warty carcinoma. Typical squamous cell carcinoma shows varying degrees of squamous maturation, whereas basaloid carcinoma is characterized by immature basal-type cells showing minimal or no squamous maturation. Warty carcinoma displays an exophytic condylomatous appearance. The squamous cells of this tumor are mature, and many show koilocytotic atypia characterized by a variable degree of nuclear atypia and cytoplasmic vacuolization. The adjacent epithelium was classified as squamous hyperplasia, lichen sclerosus, or vulvar intraepithelial neoplasia (VIN). VIN was subdivided into basaloid or warty VIN using similar criteria as for the invasive carcinomas. Overall, HPV 16 was detected in 11 cases and HPV 18 in two; none of the cases were positive for HPVs 6/11. HPV was detected in four (21%) of 19 squamous cell carcinomas, six (75%) of eight basaloid carcinomas, and three (100%) of three warty carcinomas. The adjacent epithelial lesions also showed a close correlation with the tumor type and presence of HPV. Fourteen (74%) squamous cell carcinomas had adjacent squamous hyperplasia; all of these squamous hyperplasias were negative for HPV. In contrast, seven (87%) of the basaloid carcinomas had adjacent basaloid-VIN and HPV 16 was detected within the VIN in three. Three warty carcinomas (100%) had adjacent warty VIN or basaloid VIN, and HPV was detected within VIN in two. The mean age of women with squamous cell carcinoma was 77 years, for women with basaloid carcinoma 54 years, and for those with warty carcinoma 47 years. The mean age of women with HPV-negative tumors was 77 years compared with 55 years for women with HPV-positive tumors (p less than 0.01). Thus, there appears to be a close correlation between the presence of HPV, specific subsets of invasive carcinoma and VIN, and age.(ABSTRACT TRUNCATED AT 400 WORDS)
对30例浸润性外阴鳞状细胞癌进行了临床、病理及分子病毒学分析，以研究人乳头瘤病毒（HPV）与该肿瘤的关系。通过聚合酶链反应检测病毒的存在，并通过外阴切除标本石蜡切片的原位杂交将其定位在肿瘤及相邻上皮中。利用35S标记的反义RNA探针通过原位杂交以及使用E6基因片段的HPV型特异性引物通过聚合酶链反应，随后对扩增产物进行Southern杂交，检测标本中HPV 6、11、16和18的核酸序列。这些病例分为典型鳞状细胞癌、基底细胞癌和疣状癌。典型鳞状细胞癌表现出不同程度的鳞状成熟，而基底细胞癌的特征是未成熟的基底样细胞，显示出极少或没有鳞状成熟。疣状癌呈现外生性湿疣样外观。该肿瘤的鳞状细胞成熟，许多显示出挖空细胞异型性，其特征为不同程度的核异型性和细胞质空泡化。相邻上皮分为鳞状增生、硬化性苔藓或外阴上皮内瘤变（VIN）。VIN使用与浸润性癌相似的标准细分为基底样或疣状VIN。总体而言，11例检测到HPV 16，2例检测到HPV 18；无一例HPV 6/11阳性。19例鳞状细胞癌中有4例（21%）检测到HPV，8例基底细胞癌中有6例（75%），3例疣状癌中有3例（100%）。相邻上皮病变也与肿瘤类型和HPV的存在密切相关。14例（74%）鳞状细胞癌有相邻的鳞状增生；所有这些鳞状增生HPV均为阴性。相比之下，7例（87%）基底细胞癌有相邻的基底样VIN，其中3例VIN中检测到HPV 16。3例疣状癌（100%）有相邻的疣状VIN或基底样VIN，其中2例VIN中检测到HPV。鳞状细胞癌女性的平均年龄为77岁，基底细胞癌女性为54岁，疣状癌女性为47岁。HPV阴性肿瘤女性的平均年龄为77岁，而HPV阳性肿瘤女性为55岁（p<0.01）。因此，HPV的存在、浸润性癌和VIN的特定亚组与年龄之间似乎存在密切相关性。（摘要截短至400字）
