GLANDULAR LESIONS OF THE UTERINE CERVIX - PROGNOSTIC IMPLICATIONS OF HUMAN PAPILLOMAVIRUS STATUS

Endocervical adenocarcinoma in situ (AIS) is believed to be a precurso r of invasive disease; however, the biologic behavior of endocervical glandular ''atypias'' (GAs) is unclear. The purpose of this study was to evaluate the potential role of GA as a precursor of adenocarcinoma by assessment of the human papillomavirus (HPV) status of glandular le sions. We analyzed by polymerase chain reaction (PCR) 69 cases within a spectrum of endocervical glandular lesions encompassing invasive ade nocarcinoma (IACA: 20 cases), AIS (21 cases), adenosquamous carcinoma (ASqCA: eight cases) and GA (20 cases) for HPV DNA sequences. Cervical adenocarcinoma is often associated with neoplastic squamous lesions ( SL). In this study, after exclusion of ASqCA, 29 (47.5%) of 61 cases o f endocervical glandular lesions were associated with an SL. The rate of HPV detection was not statistically different in adenocarcinoma wit h or without an SL (73.3% vs. 61.5%, respectively). In contrast, 64.3% of GAs with an SL (nine of 14 cases) were HPV positive, while only 16 .7% of GAs without an SL (one of six cases) were positive. These findi ngs suggest that HPV was preferentially associated with the concomitan t SL rather than the GA. To localize the HPV sequences within the lesi ons, eight of the nine HPV-positive GAs with an SL were analyzed by in situ hybridization (ISH). Four cases were positive by ISH and showed hybridization of the probe only in the nuclei of squamous epithelial c ells; in no lesion did the probe localize to the glandular epithelium. In our study, HPV infection of the glandular epithelium of GAs unasso ciated with an SL appeared to be an uncommon event. None of the GAs we re associated with low- or intermediate-risk HPV, and only the GA (whi ch was high grade) unassociated with an SL contained a high-risk virus type. The possibility must be considered that pathogenetic mechanisms for squamous intraepithelial lesions may be different from those resp onsible for intraepithelial glandular lesions.