Detección de infección por HPV en el hombre a través de la genitoscopia / Detection of HPV infection in men with genitoscopy

Se comunica los resultados del examen mediante genitoscopia de 64 varones sin lesiones clínicas, cuyas parejas sexuales tenían condilomas o CIN I, II o III. En 29 de ellos se observaron lesiones acetopositivas, que fueron confirmadas por histopatologías, como producidas por HPV. La citología, efectuada en 15 pacientes, no permitió confirmar lesiones por HPV. Se destaca la utilidad de la genitoscopia, técnica sencilla y de muy bajo costo, para el control y seguimiento de las parejas infectadas por HPV

Human papillomavirus (HPV) infection in seborrheic keratosis.

We studied 89 seborrheic keratoses. In four cases, light microscopy and electron microscopy demonstrated that seborrheic keratoses may be associated with human papillomavirus (HPV) infection.

Papilomatosis Borina: relaciones morfo-etiologicas; estudio clínico, histopatológico y ultraestructural / Bovine papillomatosis: morpho-etiologic relations; clinical, histopatologic and ultrastructural study

En el presente trabajo se trató de determinar la acción condicionante de la Ciclofosfamida (CF) en la resistencia de los pollos a la acción del virus de la encefalitis equina venezolana (EEV). Se utilizó como inmunosupresor la CF inyectada vía intraperitoneal (ip) en cantidad de 60 mg/Kg de peso y administrada en grupos de pollos a razón de 1,2 y 3 dósis, previamente infectados con virus EEV (cepa V-38, subgrupo 1-A). Se orientó el estudio fundamentalmente hacia los cambios histológicos a nivel del S.N.C.; como también los cambios hemáticos y la respuesta inmunológica en la producción de anticuerpos neutralizantes

Transdermal delivery of salicylic acid in the treatment of viral papillomas.

Healthy adult (New Zealand, Dutch Belt, and Wild) rabbits were infected with rabbit papilloma virus (Shope variety). The resultant papillomas were treated with salicylic acid in a new transdermal drug delivery system utilizing a karaya gum glycol matrix. Biopsy samples of treated papillomas were taken at 1, 2, and 3 weeks after initiation of treatment and examined by electron microscopy. The observed changes during the course of treatment indicated that the karaya gum glycol matrix effectively released salicylic acid into the stratum corneum. Further, the rate of delivery of salicylic acid was such that the desired keratolytic activity was achieved with minimal inflammatory response.

[Ultrastructural observation of human papillomavirus particles in the uterine cervix intraepithelial neoplasia].

Using transmission electron microscopy (TEM), twenty two cases of an intraepithelial lesion in the uterine cervix have been examined for the presence of human papillomavirus (HPV) particles. In 21 of these cases (95%), HPV particles were detected in the nucleus, and in 5 cases, in the cytoplasm. The distribution of the intranuclear HPV particles was classified into 4 types. In only 2 cases did the exhibited particles show a geometrical crystalline array (type I). In most cases, the exhibited particles were either seen to show an aggregate non-crystalline array (type II) or were concentrated around the chromatin (type III). Some cases also were found to show particles that were scattered sporadically in the nucleoplasm (type IV).

Laryngeal papilloma cells in culture have an altered cytoskeleton.

We have investigated the effect of human papillomavirus (HPV) transformation on cellular cytoarchitecture. Cells from laryngeal papillomas and normal epithelium were cultured in vitro. Cytoskeletal components of both types of cells were visualized by immunofluorescence, to determine whether there were any differences in the structure or distribution of the cytoskeleton. There was no significant change in microtubules. Two major components of the cytoskeleton, the intermediate filaments and the microfilaments, were altered in the papilloma cells. Polyacrylamide gel electrophoresis of isolated keratins showed differences between normal and papilloma tissue, which might explain the altered intermediate filament distribution. The changes in cytoskeletal structure may be one way in which HPVs alter cellular growth controls.

Retrovirus-induced osteopetrosis in mice. Ultrastructural evidence of early virus production in osteoblasts and osteocytes.

Newborn female strain NMRI mice were given injections of a mouse retrovirus (OA MuLV) known to induce osteopetrosis, osteoma, and lymphoma. Femur metaphyses and lumbar vertebrae were investigated ultrastructurally 3 d, 7 d and 28 d after infection. Budding, immature and mature virus was observed associated with osteoblasts and osteocytes, but not with osteoclasts or chondrocytes, 28 d after infection with the virus. No production of virus particles was observed in bone-tissue in mock-treated controls. Thus, the primary target cell for OA virus in bone appears to belong to the osteoblastic/osteocytic cell lineage.

Induction of undifferentiated tumors by JC virus in the cerebrum of rats.

Newborn Sprague-Dawley rats were inoculated intracranially with JC virus (Tokyo-1), a human polyomavirus, which had been isolated by Nagashima et al. from the autopsied brain of a patient with progressive multifocal leukoencephalopathy in Japan. Twenty-one to 70 weeks later, 21 of 27 rats developed brain tumors in the cerebrum, but not in the cerebellum. Most of the tumor cells were of an undifferentiated neuroectodermal nature and showed nuclear palisades and pseudorosettes. In some tumor cells glial fibrillary acidic protein was positive immunohistochemically, and many glial filaments were demonstrated ultrastructurally. Neuronal differentiation was not proved. Two continuous lines of cultured tumor cells were established, and T antigen of JCV (Tokyo-1) was present in both cell lines. Glial differentiation was confirmed also in the tumors produced by subcutaneous transplantation of cultured tumor cells.

Electron microscopy in assessment of the biological behavior of human papillomavirus infections in the uterine cervix.

To asses the natural history of human papillomavirus (HPV) infections in uterine cervix, currently implicated in etiology of cervical cancer, a prospective follow-up study has been conducted for 418 women at our clinic since 1981. The present communication summarized the current follow-up data of these patients, with special emphasis on detection of the virus in cervical punch biopsies, as correlated with other characteristics pertinent to the clinical behavior of cervical HPV infections. On each attendance, the patients are subjected to colposcopy accompanied either by Papanicolaou (PAP) smears or punch biopsies. The latter are analyzed for the cytopathic changes of HPV, for concomitant cervical intraepithelial neoplasia (CIN), for HPV structural proteins with IP-PAP technique as well as on transmission electron microscopy (TEM) for the presence of HPV particles. The local immunocompetent cell (ICC) infiltrates are analyzed using ANAE technique to define B cells, MPS cells and T cells and monoclonal antibodies (McAb) for T cell subsets, NK (natural killer) cells and Langerhans cells. HPV particles were disclosed with equal frequency (approx. 65%) in all three types of HPV lesions. Surprisingly, HPV particles were present in 70% of the biopsies derived from the regressed lesions (e. g. in those without histological evidence of HPV lesions), suggesting a possibility of a latent HPV infection. Presence of viral particles did not bear any direct correlations with the expression of HPV antigens, intensity or cellular composition of the ICC infiltrate, defined by ANAE or using McAb. Presence of HPV particles was not a major prognostic determinant, whereas the clinical course was most significantly influenced by the grade of HPV-associated CIN, to which regression was inversely and progression directly related. The results clearly confirm that cervical HPV infections are capable of progressing into carcinoma in situ and thus present with a natural history equivalent to that of classical CIN.

Association of HPV with human genital tumors.

Human papillomaviruses (HPV) are clearly responsible for the induction of genital lesions like condylomata acuminata, bowenoid papules, and flat condylomas. Moreover, the DNA of particular virus types (HPV 16 and 18) is found in a substantial number of invasively growing squamous cell carcinomas of the genital tract, suggesting an etiologic involvement of these viruses in tumor development. Since HPV 16 and 18 as well as other papillomaviruses (HPV 6 or 11) usually present within the benign genital warts can be found in dysplastic lesions of the uterine cervix known as putative precancerous lesions, determination of the virus type might be of diagnostic relevance. Since no type-specific serologic reagents are available, viruses can be identified by nucleic acid hybridization using radioactively labeled HPV DNAs that have been molecularly cloned as probes.

Histologic, immunofluorescence, and ultrastructural study of malignant islet-cell tumors of the pancreas induced in hamsters by BK human papovavirus.

Histologic, immunofluorescence and ultrastructural studies were performed in 17 cases of pancreatic carcinomas induced by the BK virus in Syrian hamsters, a unique model of experimentally induced malignant islet cell tumors. The tumors were composed of small, poorly differentiated cells mostly arranged in a trabecular structure. By immunofluorescence all four islet cell types were found in the tumors, though with different frequency. Insulin cells were present in 16 cases, glucagon cells in 11, somatostatin cells in 7, PP cells in 6. Thirteen tumors contained more than one cell type. Insulin cells were the most frequent cell type in 13 cases, and glucagon cells predominated in 1 case. Insulin-containing cells usually occupied a central position within tumor-cell aggregates, while the other cell types were mostly located in a peripheral position, a distribution reminiscent of that seen in normal islets. Gastrin and calcitonin immunoreactivities were not observed. Immunoreactive cells were more abundant in tumors with trabecular structure. Argyrophil cells revealed by the Grimelius method often exceeded the cumulative number of immunoreactive cells in the same tumor, which suggests that there were additional cell types. Multiple cell types were also found in liver metastases. Ultrastructurally most neoplastic cells were poorly granulated. The occurrence of many damaged cells suggests hormone leakage, which may account, at least in part, for the deregulated hormone release from the tumors.

Verrucous carcinoma: a possible viral pathogenesis.

Seventeen cases of verrucous carcinoma of the oral cavity were reviewed. It was found that cytologic features generally associated with viral modification were observed in 15 of these cases. This finding suggests that viruses may play some role in the pathogenesis of verrucous carcinoma. The hypothesis that an opportunistic, persistent virus may act in concert with frank carcinogens to promote the development of verrucous carcinoma is discussed.

Epidermodysplasia verruciformis. Clinical and light- and electron-microscopic observations during etretinate therapy.

Three patients with epidermodysplasia verruciformis (EV) were treated with etretinate for 9-13 months. The patients had lesions characteristic of EV, including flat warts, common genital warts, pityriasis-versicolor-like lesions and malignant changes such as actinic keratosis and Bowenoid cancer in situ. During etretinate treatment, some flattening of the warts was observed in all three patients, and the lesions on the chest and back became less red and scaling. However, none of the lesions disappeared completely, and when the treatment was discontinued, the lesions relapsed. No malignant changes were detected during the period of therapy. Electron microscopy revealed the presence of typical large, clear cells containing viral particles in the upper epidermis. Etretinate therapy induced the same type of fine-structural changes as those seen in keratinization disorders and genodermatoses. The clear cells and virus particles persisted throughout the treatment period. More long-term, controlled studies are necessary to make possible an estimate of the curative and cancer-inhibitory effect of etretinate treatment in patients with EV.

Immunofluorescence and electron microscopic investigations of epithelial hybrid cells derived from nasopharyngeal carcinoma (NPC-KT).

The present study was made to investigate some characteristics of the epithelial hybrid cells derived from nasopharyngeal carcinoma (NPC-KT cells) both in vivo and in vitro, using immunofluorescence and electron microscopic techniques. Immunofluorescence and electron microscopic studies have shown that the appearance of Epstein-Barr virus (EBV)-related early antigens, EB-viral capsid antigens and virus particles in nude-mouse-grown-tumour cells were rather repressed, in contrast to, in vitro culture of the NPC-KT cells. The tumours after transplantation of the NPC-KT cells to nude mice showed pathological pictures of poorly differentiated carcinoma with EBV-associated nuclear antigen and derived from the NPC-KT cells by means of cytogenetic studies. More importantly, we have detected EBV-related membrane antigens (MA) on the epithelial NPC-KT cells. To our knowledge, the presence of MA on the malignant epithelial cells of the nasopharynx have never been demonstrated. The results reported here show for the first time the presence of MA on nasopharyngeal carcinoma cells.

Female genital tumors associated with human papillomavirus infection, and the concept of genital neoplasm-papilloma syndrome (GENPS).

With the recent development of new analytic methods, notably the DNA hybridization technique, many benign and malignant gynecologic tumors including carcinoma in situ, verrucous carcinoma and some invasive carcinomas of the vulva, the vagina and the cervix are found to be associated with human papillomavirus infection. Benign warts and multiple neoplasms frequently appear synchronously or metachronously in a single patient, and thus present as the genital neoplasm-papilloma syndrome (GENPS). Various methods of human papillomavirus identification and a spectrum of benign and malignant female genital tumors proven to contain human papillomavirus are reviewed and summarized.

Human papillomavirus lesions in association with cervical dysplasias and neoplasias.

A series of 620 cervical biopsy specimens (precancerous and malignant) was assessed morphologically with special reference to the concomitant appearance of human papillomavirus lesions. Tissue samples from 346 of these biopsy specimens were stained for human papillomavirus antigens using the immunoperoxidase-peroxidase-anti-peroxidase (PAP) technique. Papillomavirus lesions were found in 55.6% of the biopsy specimens associated with all degrees of epithelial atypia. The mean age of the women with papillomavirus (condylomatous) changes was significantly lower (P less than .0001) than that of women without these lesions, ie, those who had dysplasia/neoplasia without concomitant papillomavirus changes. Flat and inverted condylomas were most frequent between the ages 20 and 39 and were accompanied by more severe dysplasias than the papillomatous condylomas. In immunoperoxidase-PAP staining, 56% of the papillomavirus lesions were positive, the positivity being inversely related to the degree of epithelial atypia, and bearing some correlation with the condyloma type (papillary 100%, inverted 70%, and flat 52%). Although the results show a clear-cut association of human papillomavirus lesions with premalignant, and to a lesser extent with malignant squamous cell lesions of young sexually active women, thus suggesting a relationship between the virus and cancer, a careful follow-up study is needed to fully elucidate this relationship.

BK virus-induced tumors in hamsters: a morphological, histochemical and ultrastructural study.

Macroscopic morphology, histology and ultrastructure of BK virus (BKV)-induced hamster and mouse tumors were investigated. Groups of animals were immunosuppressed to study the relationship between immune system and BKV oncogenesis. Ependymomas had the highest incidence, followed by tumors of pancreatic islets, osteosarcomas, lymphomas and sarcomas, sometimes associated in the same animal. All the tumors were found to be BKV specific. Ependymomas showed the shortest latency, infiltrated surrounding tissues but did not metastasize. Pseudo-rosettes were common and basal bodies were observed. Atypia and necrosis were more often present in immunosuppressed animals both for the ependymomas and for the other oncotypes. Pancreatic insulomas were frequently multinodular, possibly because of multifocal origin and metastasized to the liver. Hormone secretory granules were often found on electron microscopy. Osteosarcomas metastasized to lungs and peritoneum and showed the presence of osteoid, chondroblastoid and mixoid areas. Characteristic giant cells were present. Immunosuppression did not enhance tumor incidence and did not influence the latency period. However, neoplastic growth appeared to be more rapid and with more aggressive behavior in immunodepressed animals. These findings suggest an influence of the immune system in tumor development, whereas the virus oncogenic process seems unaffected.