Objective: To determine whether infection with oncogenic human papillomavirus (HPV) and/or altered expression of the tumor suppressor protein p53 is associated with clear-cell adenocarcinoma of the vagina or cervix.
Methods: Paraffin-embedded tissue specimens were studied from 14 women with clear-cell adenocarcinoma of the vagina or cervix. Nine women had a history of intrauterine diethylstilbestrol exposure. Human papillomavirus DNA was amplified via the polymerase chain reaction using consensus L1 primers and was detected by dot blot hybridization with a generic HPV probe and type-specific oligonucleotide probes. P53 protein was detected by immunohistochemical analysis with a mouse monoclonal antibody, DO-7.
Results: Three tumors contained HPV 31 DNA sequences. Eight tumors were HPV DNA-negative and three were indeterminate for HPV. P53 was detected in ten tumors; it was undetectable in the three tumors containing HPV 31 and in one tumor indeterminate for HPV. Three patients presented with or later developed metastatic disease. In each case, the tumor, including sites of metastasis, was HPV-negative and p53-positive.
Conclusions: These findings suggest that infections with oncogenic HPVs may be a cofactor in the development of clear-cell adenocarcinoma of the vagina or cervix, though this association is less than that reported for squamous or non-clear-cell adenocarcinomas. Prior studies have shown that detection of the p53 protein by immunohistochemistry correlates with mutations in the p53 tumor suppressor gene. The detection of p53 in HPV-negative clear-cell adenocarcinoma suggests a second mechanism in the etiology of these rare tumors.