Electron microscopic identification of papova virus in laryngeal papilloma

Abstract

Attempts to propagate a laryngeal papilloma virus in cell culture by the establishment of tissue culture lines from 27 papilloma specimens which were removed endoscopically from the larynx of 19 patients of all age groups were unsuccessful. By light microscopy, all the lesions, with one exception, exhibited the usual features of a typical squamous papilloma. Laryngeal papillomas were removed endoscopically from an adult male Caucasian on three separate occasions with intervening intervals of 13 and seven months. Tissue removed at each procedure was submitted for study. Tumor obtained from the first two operative procedures exhibited the features of a benign squamous papilloma. Histologic diagnosis of the most recent excised laryngeal neoplasm was consistent with carcinoma. Two papillomas which contained papova‐like virus when examined by electron microscopy were among the excised specimens cultured. Laryngeal papillomas were removed endoscopically on two occasions at an interval of five months from a 22‐year‐old Caucasian male who had a one‐month history of hoarseness. Electron microscopic examination of the most recently excised tissue revealed intranuclear viral particles which were in the shape of an icosahedron and measured approximately 45 mμ in diameter. The particles contained a densely staining core and were generally scattered throughout the nucleus. Occasionally, they were seen in crystalline arrays. The nuclear site of replication, their size and shape fit the description of the agents belonging to the papova virus group. Papova‐like viruses were also seen in laryngeal papillomas from an 18‐month‐old Negro child born of a mother with venereal warts. Although many attempts at propagating the human papilloma virus have been reported,1 the virus known to cause common warts has to date never been successfully grown for continuous passage in tissue culture. The difficulty in isolating the laryngeal papilloma virus in tissue culture is also apparent.2 Serial studies done on an adult laryngeal papilloma showed transition of the tumor from a benign to a malignant lesion. It is interesting to speculate on this possibly viral‐induced laryngeal malignancy. That viruses can cause malignancy in non‐human species is well known, and there is no reason to presume that man is different from such species in this respect. Clinical evidence of the transmissability of this disease from infected genital warts to the newborn was suggested by the development of laryngeal warts in the young child. The electron microscopic identification of virus in the laryngeal papilloma that is morphologically similar to the genital wart virus, supports this theory of transmissability. The ultrastructure of human laryngeal papilloma has been described previously3 and the presence of virus4 and virus‐like particles suggested;5 however, the crystalline lattice assemblies, characteristic of the papova group, have never been described heretofore. The results of these studies add strong morphologic and clinical evidence of the viral etio...

Papilomatose laríngea recorrente: experiência de 10 anos

“…A papilomatose agressiva é definida por múltiplas recorrências, com disseminação para árvore traqueobrônquica, progressão da doença antes da puberdade, atipia epitelial e desenvolvimento de carcinoma de células escamosas 4 . Quanto à etiologia, experimentos clínicos e estudos com microscopia óptica e eletrônica têm sugerido relação da papilomatose laríngea com infecções virais 5,6 . Somente com o desenvolvimento da biologia molecular e de diferentes técnicas de hibridização do DNA viral foi possível a demonstração desta relação, tendo sido confirmada pela técni-ca de PCR (polymerase chain reaction) 7,8,9 .…”

Human Papillomavirus DNA in Squamous Cell Carcinomas of the Larynx Demonstrated by in situ DNA Hybridization

“…Both the juvenile-and adult-onset laryn geal squamous cell papillomas are currently regarded as tumors caused by human papil lomavirus (HPV) [2-5, 8, 10, 13, 16, 17, 21, 24, 31, 55], This disease has been trans formed with cell-free extracts from man to dog [34], and HPV particles have been re peatedly found in the tumor cells on electron microscopy [5,36]. Using an indirect immunoperoxidase (IP-PAP) technique, HPV an tigens have been demonstrated in some 50% of such lesions [7,9,24,25], and more recently, HPV DNA sequences (HPV 6 and HPV 11) have been disclosed in both the juvenile-and adult-onset laryngeal papillo mas by DNA hybridization [15,25,27,29,33,37], Albeit the majority of these tumors have an entirely benign appearance and clinical behavior, an increasing number of reports are available on invasive laryngeal papillo mas [12], occurrence of intraepithelial ana plastic changes [2], atypia up to 20-40% of cases [32], as well as malignant transforma tion observed in laryngeal papillomas [11,13,14,18,20,26,28,30,51,54], It is also well reegonized that laryngeal papillomas may prove fatal by extending into the lower respiratory tract [23,52], A malignant change is likely to occur in severe papillo matosis of long duration with signs of spread throughout the respiratory tract [28], This is more common (3-14%) in the juve nile-than adult-onset papillomas [54], There are reports on malignant transforma tion of the solitary adult-onset lesions as well [28,53], commonly associated with ra diation therapy [14,26,28], However, sev eral occasions have been reported where malignant transformation...…”

Evidence for Papillomavirus Genus-Specific Antigens and DNA in Laryngeal Papilloma

“…The hypothesis for a papillomavirus etiology has been the very rare observation of intranuclear crystalline arrays of papovavirus-like par ticles in the nuclei of tumor cells [10,11] and transmission experiments in which typical verrucae arose at the site of inoculation in human volunteers after 3-6 months [12]. How ever, previous attempts to isolate papilloma virus or detect papillomavirus DNA in JLP have been unsuccessful [13,14], This remarkable plurality of human papil lomaviruses has made it difficult to detect virus antigens or nucleic acids in tumor tissue which may contain an uncharacterized virus.…”