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A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the &globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a "condylomatous" appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus-16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV-positive women were younger than HPV-negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles. Cancer 67:1599-1607,1991. HERE IS PERSUASIVE clinical, pathologic, and epi-T demiologic evidence indicating that invasive carci-noma of the cervix is preceded by a precursor lesion designated dysplasia carcinoma in situ (CIS) or cervical in-traepithelial neoplasia (CIN).' In addition, molecular virologic studies over the last 10 years have demonstrated that human papillomavirus (HPV) types 16 and 18, and to a lesser extent HPV types 3 1, 33 and 35, have a strong association with both CIN and invasive cancer. These HPV types are found in approximately 80% of both preinvasive and invasive In contrast, the role of HPV in the pathogenesis of in-vasive carcinoma of the vulva is poorly understood. To begin with, the invasive potential of the precursor vulvar intraepithelial neoplasia Grade 3 lesion (VIN 3), although not well defined, is generally thought to be low in the patient younger than age 60 years and well-documented cases of spontaneous regression of untreated CIS have been r e p ~ r t e d. ~ Also, studies evaluating the adjacent ep-ithelium to invasive vulvar cancer demonstrate CIS in only 20% to 32% of whereas CIS has been reported I599

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Reaction of dibromothiophenes with p-phenylenediamines under Ullmann condensation conditions proceeds to form copoly(thiophenediyl-l,4-diaminophenylenes). The reaction temperature had a dramatic effect on the structure of the final product. Thermal decomposition of the thiophene rings led to a fused ladder type polymer with limited solubility. Detailed thermal, spectroscopic, and analytical data afforded the complete characterization as well as established the means of distinguish between fused and unfused systems. Soluble fractions of the polymers allowed characterization of the molecular weight distribution, which gave insight into the morphology of the materials. Preliminary measurements (degenerate four-wave mixing) have demonstrated appreciable third-order nonlinear optical responses ( (3) of approximately 4 X 10-10 esu) and high laser damage thresholds (4 GW/cm2).1