Epstein-Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus.

The Epstein-Barr virus (EBV) is consistently associated with undifferentiated nasopharyngeal carcinoma (NPC). There is, however, conflicting evidence as to whether squamous cell NPCs are also EBV-associated. Moreover, it has been proposed that other epithelial tumours, particularly thymomas and thymic carcinomas, should be included in the group of EBV-associated neoplasias. However, since the viral DNA in these studies was demonstrated only in extracted DNA, the cellular origin of the viral DNA is uncertain. We have therefore investigated 152 epithelial tumours from various sites for the presence of EBV-DNA by in situ hybridization with 35S-labelled probes. Sixty-eight of 77 undifferentiated NPCs showed an EBV-specific autoradiographic signal, thus confirming the strong association of this tumour type with EBV even in geographical areas where undifferentiated NPC is not endemic. None of eight squamous cell NPCs showed an EBV-specific signal. All of 15 carcinomas with a similar morphology to undifferentiated NPC but from different anatomic sites (thymus, tonsil, breast) were EBV-negative as were 9 thymomas, 26 squamous cell carcinomas of the palatine tonsil, and 14 cervical carcinomas. Our results therefore suggest a unique association of EBV with undifferentiated NPC and support concepts assigning different biological properties to undifferentiated NPC as compared with squamous cell NPC.

Detection of human papillomavirus type 16 DNA in carcinomas of the palatine tonsil.

Twenty eight tonsillar carcinomas of various histological types were investigated for the presence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) types 6, 11, and 16 by in situ hybridisation using highly stringent procedures. In six cases an autoradiographic signal was obtained in the tumour cell nuclei with the HPV type 16 specific probe. No signal was obtained with any of the other probes. Immunohistochemical investigations with mouse monoclonal antibodies directed against the L1 protein of HPV type and a rabbit antiserum that detects common protein determinants of HPV gave negative results, thus indicating latent infection. Furthermore, a series of tonsils from controls with comparable age distribution was negative by both in situ hybridisation and immunohistology. These results indicate a possible role for HPV 16 in the aetiology of a proportion of tonsillar carcinomas.

[Demonstration of DNA tumor viruses in carcinomas of the upper respiratory tract]. / Nachweis von DNS Tumorviren in Karzinomen des oberen Respirationstraktes.

In situ hybridization (ISH) using 35S-labeled probes was applied to the detection of viral DNAs in 115 epithelial tumours from various sites. Epstein-Barr virus (EBV) DNA was detected in 83% of undifferentiated nasopharyngeal carcinomas (NPC) while none of seven squamous cell NPC displayed an EBV-specific autoradiographic signal. Also, all other tumours investigated, including thymomas, thymic carcinomas, tonsillar carcinomas and medullary breast carcinomas were negative upon ISH to EBV-specific probes. These results suggest a unique association of undifferentiated NPC with EBV. 28 tonsillar carcinomas were further analyzed for the presence of human papillomavirus (HPV) DNA. Six carcinomas showed an HPV16-specific signal while hybridization to HPV6- and HPV11-specific probes yielded negative results. No HPV-DNA was detected in any of 30 tonsils with chronic inflammation, thus excluding that the finding of HPV16 in a proportion of tonsillar carcinomas is merely circumstantial. These results point to a possible etiologic role of HPV16 in the pathogenesis of some tonsillar carcinomas.