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PIP: Human papillomavirus (HPV) infection has been implicated in the intraepithelial cervical changes that cause most abnormal Papanicolaou smears. To date, 14 types of HPVs have been identified. All are small, nondeveloped, icosahedral DNA viruses that share a common internal antigen. In cases of cervical HPV infection, the koilocytes and dyskeratocytes are the most frequently seen cell types. Most infections are flat aceto-white lesions. Florid condyloma acuminatum, usually detectable with the naked eye, is characterized by an irregular surface secondary to finger-like projections, in the middle of which a capillary loop comes to the surface. Spiked condyloma, not seen with the naked eye, has an irregular surface that shows asperity. 3 techniques have been used to differentiate atypical condyloma from intraepithelial neoplasia: microspectrophotometric studies, the peroxidase- antiperoxidase technique, and electronmicroscopy. There is growing evidence that papillomaviruses play an etiologic role in human genital cancer. 20-25% of dysplastic and neoplastic lesions show a coexistence of condylomas of the cervix or vulva with dysplasia or neoplasia. Epidemiologic research suggests that cervical condylomas occur at a mean age of 27.5 years, precede cervical dysplasia by 3.3 years, carcinoma in situ by 9.3 years, and invasive carcinoma by 27.4 years. The conversion of most cases of papillomas into squamous cell carcinomas requires the presence of carcinogenic initiators, 1 of which is believed to be herpes simplex virus.^ieng

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Twelve biopsies from condylomatous lesions of the human cervix were examined by transmission electron microscopy in order to study koilocytotic cells. The ultrastructure of koilocytes, revealed mainly cytoplasmic changes in the perinuclear area. These changes first appeared in cells of the intermediate layers and extended to the surface of the epithelium. The cells involved showed small perinuclear areas, with a fine granular material, which appeared as a lysis of the cytoplasmic matrix, forming microvacuolelike structures that gradually enlarged and fused together, ending with the formation of a large clear zone (koliocytosis). Binucleation and polylobulation were constant features. Intranuclear virus particles were often associated with koilocytes. Tubules and large bundles or single filamentous structures were also observed in koilocytes detected in smears and biopsies. This study provides further evidence that the koilocytes is the result of a process characterized by cellular changes due to cytopathogenic effect of the human papillomavirus.

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In our clinic, as a rule, we do not treat vaginal condylomata. They are usually subclinical and asymptomatic. When atypia is present on biopsy, they should be treated in the same manner as vaginal intraepithelial neoplasia. When vaginal discharge and pruritus are present, infection should be searched for and treated. When condylomata are seen with the naked eye, colposcopy has shown that there were many more, too small to be seen, so that local therapy seems a waste of time. If on colposcopic examination only a few condyloma acuminata are located, then therapy is defendable. CO2 laser therapy should be preferred to other modalities until a systemic treatment is available and safe.

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The peroxidase-antiperoxidase technique with the use of paraffin sections of 67 cervical biopsy specimens and an antiserum cross-reactive with all papillomaviruses provided immunologic confirmation for the observation that papillomavirus infection of the cervix is not uncommon and that it most often presents as a flat, colposcopically unremarkable lesion. Papillomavirus antigen was detected in 21 or 35 condylomata of the cervix. Antigen-positive nuclei were found in the upper layers of the epithelium. Electron-microscopic examination of five reprocessed antigen-positive sections revealed, in each instance, papillomavirus particles in the nuclei of the most superficial layers of the condylomatous epithelium. The viral antigen was not detected in dysplasia, carcinoma in situ, or invasive carcinoma.

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We report on 162 cases of human papillomavirus (HPV) infection of the cervix seen in a two-year period in which the cell sample showed such marked atypia that errors of interpretation could easily have been made. These atypical condylomata are difficult to diagnose cytologically as well as histologically because they mimic dysplasia or carcinoma in situ and, on smears, even invasive squamous carcinoma. HPV particles associated with fibrillar material were found within nuclei of these lesions; their nature was further proved by the immunoperoxidase test. This new form of HPV infection of the cervix showed a 9.1% rate of progression to more advanced cervical lesions. The cytologic finding of atypical condylomata is an indication for colposcopy, confirmative biopsy and appropriate treatment.

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Sterile sequentially extracted insoluble bone matrix gelatin and freeze-dried allogeneic demineralized whole bone matrix was implanted into a lumbar muscle pouch of 12 Sprague-Dawley rats fed a diet containing 0.9 ppm zinc and into 6 rats fed a diet containing 50 ppm zinc. Histological sections and microradiography demonstrated that skeletal tissue induction occurred in all instances. In the zinc-supplemented hosts, four weeks postimplantation, trabecular bone and bone marrow grew on both sides of the matrix implant which had been almost completely resorbed by matrixclast activity. However, in the zinc-deficient hosts, the central cavity of the matrix was first filled with mesenchyme and then cartilage cells which grew in the form of thin wedges into the implanted matrix. Poor vascularization appears to be an important factor in cell proliferation and abnormal differentiation in zinc deficiency.

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