Theodore D. Kessis

Probable nonpapillomavirus etiology of squamous cell carcinoma of the vulva in older women: a clinicopathologic study using in situ hybridization and polymerase chain reaction.

Summary: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 car-cinomas had adjacent basaloid-VIN andHPV 16was detected within the VIN in three. Theree warty carcinomas (100%) hadadjacent warty VIN or basaloid VIN, and HPV was detedted within VIN in two. The mean age of women with squamouscell carcinoma was 77 years, for women with basaloid carcinoma 54 years, adn forthose 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 > 0.01).Thus, there appears to be a close correlation between the presence of HPV, specivic subsets of invasive carcinomaand VIN, and age. These data suggest that vulvar cancer has a diverse etiology which in young women in HPv-related but in older women has little association with HPV.

Polymerase chain reaction identification of human papillomavirus DNA in CO2 laser plume from recurrent respiratory papillomatosis.

Human papillomavirus (HPV) DNA was identified in the plume produced during CO2 laser vaporization of respiratory tract papillomata. The plume produced from CO2 vaporization was collected on Gelfoam pledgets that were affixed to suction tips evacuating the vapor plume from the operative field. The Gelfoam pledgets were snap frozen in liquid nitrogen, processed, and examined for HPV-6 and HPV-11 DNA by a polymerase chain reaction technique. Tissue and vapor-plume specimens were collected from 22 patients undergoing CO2 laser excision of laryngeal lesions. Seven patients had adult-onset recurrent respiratory laryngeal papillomatosis (RRP), 12 had Juvenile-onset RRP, two had laryngeal carcinoma, and one had nonspecific laryngitis. HPV-6 or HPV-11 was identified in 17 of 27 vapor-plume specimens from RRP and in none of three from non-RRP lesions. All but one RRP tissue specimen contained HPV-DNA, and none of the non-RRP tissues contained HPV-DNA. When HPV was present in vapor, the same HPV type was found in the corresponding tissue specimen. Identification of HPV-DNA in the laser plume raises concern regarding potential risks from exposure to the plume—particularly to the endoscopic surgeon and the operating team. The practical concerns and effectiveness of the plume scavenging systems are discussed.

Human papillomavirus in sinonasal papillomas and squamous cell carcinoma

The diagnostic and prognostic relevance of human papillomavirus (HPV) types 6, 11, 16, and 18 in squamous papilloma, inverted papilloma, and squamous carcinoma of the sinonasal epithelium was examined using the polymerase chain reaction (PCR) technique. Four (15%) of 26 squamous papillomas, 7 (24%) of 29 inverted papillomas, and 1 (4%) of 24 squamous carcinomas were positive for HPV when examined using the PCR amplification technique.

Human papillomavirus investigation of patients with cervical intraepithelial neoplasia 3, some of whom progressed to invasive cancer.

The major objective of the study was to determine if the contrasting frequencies (1.5% vs. 22%) of progression of cervical intraepithelial neoplasia (CIN) 3 lesions to invasive cervical carcinoma in two groups of patients in a previously published study from New Zealand had a virologic basis. Archival tissues on which the original diagnosis of CIN 3 was made were examined. Paraffin sections of 81 CIN 3 lesions from each group were tested for the presence of human papillomavirus (HPV)-6, -11, -16, and -18 DNA sequences by a combination of in of in situ hybridization for viral transcripts and polymerase chain reaction for viral DNA. The virologic profiles of the two groups were similar; HPV-16 and HPV-18 were identified, respectively, in 62% and 6% of CIN 3 lesions of group 1 and in 60% and 2% of CIN 3 lesions of group 2. additional tissues were examined for 17 women of group 2, who progressed from CIN 3 invasive cancer. Progression to invasive cancer was not associated with infection with specific HPV types. It is concluded that the contrasting frequencies of progression to invasive carcinoma in two groups of New Zealand women were not attributable to differences in HPV type distribution in the original CIN 3 lesions of these two groups.