Detection of human papillomavirus in large cell neuroendocrine carcinoma of the uterine cervix: a study of 12 cases

Aim: To investigate the role of human papillomavirus (HPV) in large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix. Methods: Twelve archival, immunohistochemically and/or electron microscopically confirmed cases of cervical LCNEC were studied. Non-isotopic in situ hybridisation (NISH) was performed on the formalin fixed, paraffin wax embedded biopsies using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31, and 33. The tumours were then subjected to polymerase chain reaction (PCR) analysis using GP5+/GP6+ consensus primers to the HPV L1 gene, in addition to type specific primers to the E6 and E6/E7 genes. Results: HPV-16 was detected by NISH and/or PCR in seven of the 12 carcinomas. Two additional tumours were HPV-18 positive by NISH and/or PCR. HPV DNA was not detected in the three remaining cases. Conclusion: Integration of high risk HPV, in particular type 16 and to a lesser extent type 18, is associated with this uncommon variant of cervical carcinoma.