High-risk human papillomavirus seems not involved in DES-related and of limited importance in nonDES related clear-cell carcinoma of the cervix

ObjectiveOver 90% of all cervical adenocarcinoma are caused by a transforming infection with a high-risk type human papillomavirus (hrHPV). Previous studies demonstrated that the association between hrHPV positivity and cervical clear-cell adenocarcinoma (CCAC) varies between 0% and 100%. As approximately 60% of all CCAC are associated with intra-uterine diethylstilbestrol (DES) exposure, we determined in a cohort of both DES-exposed and DES-unexposed women the prevalence of hrHPV infections, and the potential etiological role of hrHPV by additional analysis of p16INK4a and p53 expression.MethodsRepresentative slides of 28 women diagnosed with CCAC were tested for hrHPV by two PCR methods (the clinically validated GP5+/6+ PCR and the very sensitive SPF10PCR/LiPA25). Fifteen women were DES-exposed, 10 unexposed and of 3 women DES-exposure was unknown. Twenty-one cases with sufficient material were immuno-histochemically stained for p16INK4a and p53.ResultsSeven tumors, of which four DES-exposed and two unexposed tested positive for hrHPV with GP5+/6+ PCR. Thirteen tumors, of which five DES-exposed and seven unexposed, tested positive with SPF10PCR/LiPA25. In one women with unknown exposure, a CCAC tested positive in both assays. Only three cases, none in DES-exposed women, and all positive with both hrHPV assays, revealed diffuse p16INK4a immuno-staining and weak p53 staining as well, supporting indisputable hrHPV involvement.ConclusionsAlthough the prevalence of hrHPV was high, only two DES-unrelated CCAC (25%) and one tumor in a woman with unknown exposure could be attributed to hrHPV.

Research highlights► The majority of all clear-cell adenocarcinomas are associated with DES-exposure. ► In DES-related tumors no causal role of hrHPV could be identified. ► In DES-unrelated tumors, 20–25% are hrHPV mediated.