Recent molecular
biologic studies have shown that some type of human papillomavirus (HPV) is closely associated with
uterine cervical cancer. In order to investigate the relationship between HPV
DNA and
cervical cancer, we studied the
carcinogenesis of HPV in
cervical cancer and related lesions by dot blot hybridization (D.B.H.), Southern blot hybridization (S.B.H.), in situ hybridization (I.S.H.) and polymerase chain reaction (P.C.R.). We also followed some HPV
DNA,
mRNA positive or negative cases of
cervical dysplasia for more than 16 months prospectively. I. Analysis of HPV
DNA HPV
DNA were detected in
cervical dysplasia and
cancer and HPV positive rate increased as the grade of
cervical dysplasia became higher by several molecular
biologic analysis. Especially, the results of I.S.H. with biotinylated
HPV DNA probes revealed that HPV
DNA was located in the nuclei of koilocytosis, dysplastic cells and
cancer cells. In analysis of HPV type in squamous epithelium, HPV 6/11 was the highest positive rate (21.1%) in mild dysplasia. On the other hand, HPV16 positive rate increased with the grade of dysplasia and 34.9% (15/42) of moderate dysplasia and 51.4% (18/35) of severe dysplasia were positive for HPV 16
DNA, respectively. And N/C ratio in HPV 16 positive cells significantly increased by measurement of micrometer. These findings suggest that HPV 16 is high risk HPV and associated with squamous epithelial
neoplasia. About 50% of
metaplasia close to cervical
neoplasia with HPV
DNA was positive for the same type of HPV. In columnar epithelium, several types of HPV
DNA were detected in 46.7% (15/32) of cervical
adenocarcinoma. Thirty one percent (10/32) of
adenocarcinoma, 50% (4/8) of adenosquamous cell
carcinoma were positive for HPV 18. This suggests an association between HPV 18 and
adenocarcinoma and related lesions. We examined amplified
DNA detection of HPV 16 and 18 E7 gene by P.C.R. method. HPV 16 and/or 18
DNA were detected in 25 of 43 cases of cervical scrapes obtained from cervical
neoplasia, and we confirmed the P.C.R. is the useful method for the screening and the retrospective investigation of
HPV infection. By the immunohistochemical and molecular
biologic study, there was no correlation HPV
DNA with c-myc product and c-myc gene amplification. II. Analysis of HPV
mRNA (E6/E7, L1/L2) The early genes E6/E7 of HPV 16 and 18 were considered as one of the carcinogenic factors of uterine cervix. We investigated the localization of HPV E6/E7 and L1/L2
mRNA in
cervical dysplasia and CIS with I.S.H. using antisense and sense biotinylated HPV
RNA probes which were made by in vitro transcription.(ABSTRACT TRUNCATED AT 400 WORDS)