Analysis of individual human papillomavirus types in cervical neoplasia: a possible role for type 18 in rapid progression.

Histologic and molecular analyses of 214 cervical biopsy specimens were performed to test the hypothesis that certain individual human papillomavirus types that are usually grouped together are differentially distributed in various grades of cervical intraepithelial neoplasia and invasive squamous carcinoma. Specifically, types 16 and 18, which are commonly grouped together, were analyzed separately and compared. Biopsies obtained from three different geographic sites in the United States and Brazil were analyzed by Southern blot hybridization and correlated with the histologic diagnosis from the same tissue sample. There was a highly significant correlation between papillomavirus type and histologic grade comparing all grades of cervical intraepithelial neoplasia with invasive cancer (p less than 0.001). Of particular interest was the striking deficit of type 18 in intraepithelial neoplasia (3%) as compared with invasive carcinoma (22%; p less than 0.001). In contrast, there was no significant difference in the distribution of type 16 in intraepithelial neoplasia (37%) as compared with invasive carcinoma (41%). The deficit of type 18 in intraepithelial neoplasia compared with invasive carcinoma could represent a rapid transit time through the precursor stage. Human papillomavirus type 18 may therefore play a role in the development of rapidly progressive cervical cancer.

Oncogenic association of specific human papillomavirus types with cervical neoplasia.

Molecular hybridization analysis of human papillomavirus (HPV) DNA from 190 cervical biopsy specimens from women in the United States, Brazil, and Peru revealed viral sequences in 2 (9%) of 23 biopsy specimens of normal mature squamous epithelium, 7 (44%) of 16 biopsy specimens of metaplastic squamous epithelia, 60 (77%) of 78 cervical intraepithelial neoplasia (CIN), 57 (89%) of 64 invasive squamous carcinomas, and 8 (89%) of 9 endocervical adenocarcinomas. HPV typing by DNA hybridization revealed HPV 6 and HPV 11 sequences in metaplastic squamous epithelia, CIN I, and CIN II, but not in CIN III lesions or invasive carcinomas. HPV 16 was detected in metaplastic epithelium and in nearly half of the invasive squamous carcinomas and adenocarcinomas. It was present in 31% of CIN lesions, increasing in frequency with the severity of CIN from 20% of CIN I to 50% of CIN III. HPV 16 showed a striking difference in geographic distribution, being detected in 36% of the carcinomas from the United States compared to 64% of the carcinomas from Brazil and Peru. HPV 18 was found in metaplastic epithelia and in 17% of carcinomas but in only 1% of CIN lesions. HPV 31 was not found in metaplastic epithelium but was present in 6% of carcinomas and in 18% of CIN lesions. In addition, a group of uncharacterized HPVs, not corresponding to any of the probes used, was found in 5% of normal and metaplastic epithelia and in 18% of CIN and 19% of invasive cancers. These results suggest that individual HPV types that infect the cervix have varying degrees of oncogenic association. HPV 6 and HPV 11 appear to have very little oncogenic association, HPV 31 has low oncogenic association, and HPV 16 and HPV 18 have high oncogenic association.