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

Abstract.

To evaluate the importance of high-risk human papillomavirus (HPV) types in in situ and invasive adeno- and adenosquamous carcinomas (ACISs/ACs, and ASCISs/ASCs) of the cervix uteri, we analyzed HPV infection and HPV 16- and HPV 18 E6/E7 oncogene expression in different histologic subtypes. Using the 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 HPV 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 for HPV 16 and HPV 18. In ACISs/ASCISs, HPV 16 oncogene expression predominated (62%) relative to HPV 18 (25%) expression, whereas in invasive ACs/ASCs, only 21% of the cases expressed HPV 16, but 48% of the cases expressed HPV 18 oncogenes. Thus, detection of HPV 18 in ACISs/ASCISs might be associated with an increased risk of progression. HPV oncogene expression was not dependent on histologic subtype of in situ or invasive AC. Normal glandular epithelia and glandular dysplasias (GDs, n=4) were always negative concerning HPV oncogene expression. In HPV 16- and HPV 18-double-infected 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 purely glandular lesions or in cases with an additional CIN (cervical intraepithelial neoplasia) II or CIN III. HPV E6/E7 expression of the same HPV type in both in situ or invasive ACs and associated CIN II/III suggest that these lesions might be histogenetically related.