Differences in HPV 16- and HPV 18 E6/E7 oncogene expression between in situ and invasive adenocarcinomas of the cervix uteri

To evaluate the importance of high-risk human papillomavirus (HPV) types in in situ and invasive adeno- and adenosquamous carcinomas (ACISs/ACs, and A SCISs/ASCs) of the cervix uteri, we analyzed HPV infection and HPV 16- and HPV 18 E6/E7 oncogene expression in different histologic subtypes. Using th e polymerase chain reaction (PCR) technique, 29 of 33 (88%) ACISs, 2 of 2 ( 100%) ASCISs, 46 of 54 (85%) ACs, and 8 of 10 (80%) ASCs were found to be H PV 16- and/or HPV 18-positive. In 25 of 35 (71%), 10 of 35 (29%), and 4 of 35 (11%) ACISs/ASCISs, HPV 16, HPV 18, and HPV 16 and HPV 18 were detected, respectively. Invasive ACs/ASCs were more frequently infected with HPV 18 (36 of 64, 56%) than with HPV 16 (28 of 64, 44%). Ten (16%) of these cases were positive of HPV 16 and HPV 18. In ACISs/ASCISs, HPV 16 oncogene expres sion predominated (62%) relative to HPV 18 (25%) expression, whereas in inv asive ACs/ASCs, only 21% of the cases expressed HPV 16, but 48% of the case s expressed HPV 18 oncogenes. Thus, detection of HPV 18 in ACISs/ASCISs mig ht be associated with an increased risk of progression. HPV oncogene expres sion was not dependent on histologic subtype of in situ or invasive AC. Nor mal glandular epithelia and glandular dysplasias (GDs, n=4) were always neg ative concerning HPV oncogene expression. In HPV 16- and HPV 18-double-infe cted cases, HPV 18 oncogene expression was most frequently detected, and we did not find a coexpression of HPV 16- and HPV 18-specific oncogenes in pu rely glandular lesions or in cases with an additional CIN (cervical intraep ithelial neoplasia) II or CIN III. HPV E6/E7 expression of the same HPV typ e in both in situ or invasive ACs and associated CIN II/III suggest that th ese lesions might be histogenetically related.