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Rotating mass shells with flat interiors are of interest with respect to the definition of a gravitational field energy density and with respect to the question of relativity of rotation. Previous work on quasispherical rotating mass shells is extended to more general shell shapes. An analysis of the Dirichlet problem for the stationary Einstein equations-which is of considerable interest by itself-shows that for a given non-spherical shell shape in general no mass distribution and no degree of differential rotation on it can realise flatness in the interior. This is explicitly proven in the lowest order of the 'rotation parameter' for mass shells which deviate infinitesimally from a sphere.

The lower limit of the total mass-energy of asymptotically flat initial geometries in five-dimensional Kaluza-Klein theory is shown to be negative for topologies on spacelike surfaces of the bubble (R2×S2) type. The lower limit is related to the size of the bubble rather than to the compactification scale, and can be arbitrarily negative.

Solitary keratoacanthomas of 32 patients were screened for the presence of human papillomavirus (HPV) 25 DNA, which was originally isolated and molecularly cloned from warts of an epidermodysplasia verruciformis (Ev) patient. Biotinylated virus DNA was hybridized in situ to thin sections obtained from paraffin-embedded material. HPV DNA was detected in 12 of 32 tumors under stringent conditions, and in 2 additional tumors under relaxed conditions.

Bacterial strain 16-12 was isolated from the root nodules of lupines and was found to be mitomycin C-inducible for the production of a bacteriophage (“16-12-1”) with a long noncontractile tail. The phage was found to attach with a fork-like terminal tail structure to the pili of strain 16-12. In addition, it was also found adsorbed to the bacterial cell poles. It is suggested that phage 16-12-1 may be pilus dependent.

Human papillomavirus (HPV) 8 induces skin tumors which are at high risk for malignant conversion. The nucleotide sequence of HPV8 has been determined and compared to sequences of papillomaviruses with different oncogenic potential. The general organization of the HPV8 genome is similar to that of other types. Highly conserved, genus-specific sequences were found in open reading frames (ORFs) E1, E2, and L1. In ORFs E6, E7, and L2, HPV8 is more distantly related, but it was possible to differentiate subgenera in which HPV8 belonged to the HPV1-cottontail rabbit papillomavirus group. Sequences within ORF E4 and part of ORF L2 are rather type specific. HPV8 stands out by several unique features: the considerably reduced size of the noncoding region (397 base pairs), with a seemingly low potential for forming complex secondary structures; a cluster of putative promoter elements in the 3' half of ORF E1; an RNA polymerase III promoter-like sequence close to the C terminus of ORF E2; and of particular interest, the homology between the putative protein encoded by ORF E4 and the Epstein-Barr virus nuclear antigen 2 protein, which may reflect similar mechanisms in virus-mediated transformation.

Within a dynamic theory of fusion the three-particle-system is examined. Under suitable boundary conditions a method of integra ion is developed, which yields the exact solution of the relativistic three-particle-equation. This solution describes an elementary particle with internal structure. A thorough discussion of the collective motion supplies the massM and spin 1/2 for the new particle and the proper Diracequation, so that an identification of the three-particle-system with the electron is possible.

DNA of human papillomaviruses has frequently been detected in nonmelanoma skin cancers, raising the question of a possible causal contribution of these tumor viruses to skin carcinogenesis. Basal cell carcinomas are the most common nonmelanoma skin cancers; however, so far they are only poorly analyzed with regard to human papillomavirus infection. We searched for human papillomavirus-DNA in 69 biopsies from 61 immunocompetent basal cell carcinoma patients from two geographic locations in Europe using six different polymerase chain reaction primer systems. We could demonstrate human papillomavirus-DNA in 43.5% of the tested tumors. Human papillomavirus positivity did not seem to correlate with the duration of disease or patients' age. The vast majority of virus types in the biopsies belonged to the group of epidermodysplasia verruciformis-associated human papillomavirus. Of 31 sample pairs tested for human papillomavirus-DNA in tumors as well as in perilesional healthy skin, seven carried viral sequences in lesional and healthy skin and three only in the basal cell carcinoma. Six of the seven human papillomavirus-positive basal cell carcinoma/healthy skin pairs contained identical human papillomavirus types in tumors and histologically normal tissue. Forty basal cell carcinoma patients were additionally analyzed for IgG antibodies against virus-like particles of three representative epidermodysplasia verruciformis–human papillomavirus types: 8, 15, and 36. No statistically significant differences could be detected between human papillomavirus antibody prevalences of basal cell carcinoma patients and of dermatologically healthy individuals. Moreover, serologic findings did not correlate with the detection of specific human papillomavirus types in tumors. Our results seem to suggest that the occurrence of human papillomavirus-DNA in basal cell carcinoma does not reflect a major etiologic role of human papillomavirus in this cancer.

Recent studies have demonstrated a high prevalence of human papillomavirus (HPV) types originally believed to be restricted to patients with epidermodysplasia verruciformis (EV) in benign and malignant skin tumors of the general population. Other groups detected typical mucosal HPV in skin tumors. We have investigated recurrent leukoplakial cutaneous and mucosal lesions located around the ileostoma of a woman with ulcerative colitis for the presence of HPV. Cutaneous, mucocutaneous, and mucosal ileostoma-biopsies were analyzed by three different polymerase chain reaction protocols for genital, cutaneous, and cutaneous EV-associated HPV types. Polymerase chain reaction products were cloned, sequenced, and submitted to phylogenetic analyses. HPV-DNA sequences of the EV-HPV group could be detected in all biopsies, whereas genital/mucosal or cutaneous HPV types were not found. HPV types detected comprised HPV20, HPV23, HPV38, and four putatively novel HPV types that belong to different clusters of the EV-HPV group B1. Different HPV types prevailed in cutaneous, mucocutaneous, and mucosal lesions and the number of HPV sequences found per lesion varied between one and three. Our data show the association of recurrent lesions around a stoma and at the ileum with known and novel EV-HPV types. These results emphasize the plurality of HPV and yield data for the possible transmission of cutaneous HPV to mucosal areas of the intestine.

Recent studies suggest a role of cutaneous human papillomaviruses (HPV) in non-melanoma skin cancer (NMSC) development. In this study viral DNA loads of six frequent HPV types were determined by quantitative, type-specific real-time-PCR (Q-PCR) in actinic keratoses (AK, n=26), NMSC (n=31), perilesional tissue (n=22), and metastases of squamous cell carcinomas (SCC) (n=8) which were previously shown to be positive for HPV5, 8, 15, 20, 24, or 36. HPV-DNA loads in AK, (partially microdissected) NMSC, and perilesional skin ranged between one HPV-DNA copy per 0.02 and 14,200 cell equivalents (median: 1 HPV-DNA copy per 344 cell equivalents; n=48). In 32 of the 79 HPV-positive skin biopsies and in seven of the eight metastases viral loads were even below the detection limit of Q-PCR. Low viral loads in NMSC were confirmed by in situ-hybridization showing only a few HPV-DNA-positive nuclei per section. Viral loads in SCC, basal cell carcinomas, and perilesional tissue were similar. But, viral loads found in AK were significantly higher than in SCC (p=0.035). Our data suggest that persistence of HPV is not necessary for the maintenance of the malignant phenotype of individual NMSC cells. Although a passenger state cannot be excluded, the data are compatible with a carcinogenic role of HPV in early steps of tumor development.

Summary Erythroplasia of Queyrat is a carcinoma in situ that mainly occurs on the glans penis, the prepuce, or the urethral meatus of elderly males. Up to 30% progress to squamous cell carcinoma. The cause of erythroplasia of Queyrat is largely unknown. Human papillomavirus type 16 DNA has previously been detected only in very few distinctly characterized patients. We have investigated 12 paraffin-embedded biopsies from eight patients with penile erythroplasia of Queyrat and control biopsies of inflammatory penile lesions, of genital Bowen's disease, and of premalignant/malignant cervical or vulvar lesions by 10 different polymerase chain reaction protocols for the presence of cutaneous and genital/mucosal human papillomaviruses. Human papillomavirus typing was performed by sequencing (cloned) polymerase chain reaction products. Human papillomavirus DNA was detected in all erythroplasia of Queyrat patients and in none of the controls with inflammatory penile lesions. The rare cutaneous carcinogenic epidermodysplasia verruciformis-associated human papillomavirus type 8 was present in all erythroplasia of Queyrat patients and the genital high-risk human papillomavirus type 16 in seven of eight patients (88%). In addition to human papillomavirus type 8 and human papillomavirus type 16, four patients carried the genital carcinogenic human papillomavirus type 39 and/or type 51. All human papillomavirus type 8 sequences found in erythroplasia of Queyrat showed some polymorphism among each other and differed in specific nucleotide exchanges from the human papillomavirus type 8 reference sequence. Viral load determinations (human papillomavirus copies/β-globin gene copies) by realtime polymerase chain reactions showed that the human papillomavirus type 16 levels in the erythroplasia of Queyrat biopsies were one to five orders of magnitude higher than the human papillomavirus type 8 levels. Human papillomavirus type 8 was not detected in cervical or vulvar precancerous and cancerous lesions and in Bowen's disease lesions that carried genital human papillomavirus types. The data suggest that in erythroplasia of Queyrat, in contrast to other genital neoplasias, a coinfection with human papillomavirus type 8 and carcinogenic genital human papillomavirus types occurs. The presence or absence of human papillomavirus type 8 might help to distinguish between penile erythroplasia of Queyrat and Bowen's diseases.

Retinoids exert a prophylactic and therapeutic effect on chemically induced cancers and papillomas in mice [12]. In recent years, retinoid has been orally administered to patients with multiple warts induced by various human papillomavirus (HPV) types [1, 3, 6, 7, 9, 10, 14], resulting in an improvement of the lesions [1, 3, 6, 7, 9, 10]. In some cases, virus particles, structural antigens and viral D N A were no longer detectable during therapy [6, 7, 9, 10]. Soon after the discontinuation of the therapy, however, there was a recurrence of clinically and histologically identical warts that harboured the same virus tpe [3, 6, 7]. This suggest that the drug does not interfere with viral persistence, but has only a palliative effect. To investigate whether retinoids have a specific effect on the persistence and expr6ssion of papillomavirus DNA, we performed an in vitro experiment with bovine-papillomavirus-1 (BPV)-transformed C127 mouse cells [2] and mouse-embryo fibroblasts. This system was used because HPVs do not readily transform tissue-culture cells. BPV-I D N A persists in transformed cells extrachromosomally [8]. Low levels of expression can be observed: an R N A of 1,300 nucleotides represents the predominant transcript [4]. C-127 cells represent a permanently growing mouse-fibroblast cell line which is perfectly contact inhibited in growth [2]. Mouse-embryo fibroblasts were prepared from 18-days-old DBA mouse embryos according to standard protocols and were maintained in Dulbecco's modified Eagle 'smedium with 5% fetal calf serum. They were infected in the second passage

Human papillomavirus (HPV) 16 is most prevalent in cervical cancers and also persists in metastases. We examined HPV16-DNA-positive primary cancers and several lymph nodes from each of 14 patients to evaluate the use of HPV16 DNA as a diagnostic marker for the detection of early node involvement. The HPV16 DNA was exclusively integrated in 39% of the primary cancers, predominantly episomal in 36%, and integrated and extrachromosomal to a similar extent in 25%. Thirteen of 16 involved lymph nodes contained HPV16 sequences. Integrated viral DNA showed the same pattern in primary tumors and in metastases. The level of extrachromosomal HPV16 DNA, however, appeared to be considerably reduced in some nodes. HPV16 DNA was also detected in 18 out of 59 histologically negative lymph nodes. This result recommends nucleic acid hybridization as a sensitive method for the detection of HPV-DNA-positive cancer cells. The prognostic significance of viral sequences in histologically negative nodes remains to be established.

The protein compositions of full and empty particles of human papilloma viruses 1, 2, and 3 were compared by SDS-gel electrophoresis. The protein patterns revealed a considerable variation in the relative concentrations of three major proteins (VP2, 3, and 4) in individual preparations. In some cases, "heavy" and "light" full particles prepared from the same wart showed a similar variability in the concentrations of VP2, 3, and 4. The different protein patterns were interpreted as resulting from conversion of VP2 into VP3 and 4. The molecular relationship of these three proteins was confirmed by BrCN cleavage which led to corresponding oligopeptides. Electron micrographs of empty particles revealed that the only detectable protein components VP3 and 4 are present in typical capsomeres.

Focal epithelial hyperplasia Heck lesions of a Turkish patient were shown to contain papillomavirus-specific DNA, which was molecularly cloned into bacteriophage lambda. It proved to be related to human papillomavirus (HPV) type 6 DNA and HPV type 11 DNA. Reassociation kinetics revealed a cross-hybridization of 4 and 3%, respectively. There was no cross-reactivity with HPV type 1, 2, 3, 4, 5, 8, or 10. This papillomavirus type will be referred to as HPV type 13. The DNA was characterized by cleavage with several restriction enzymes, and the cleavage sites were physically mapped. Papules from two additional cases of Morbus Heck contained HPV type 13 DNA as shown by Southern blot hybridization and by the characteristic cleavage patterns. This may indicate that HPV type 13 is more frequently associated with focal epithelial hyperplasia Heck than are other HPV types.

Papillomavirus DNA from an oral papilloma of a beagle was characterized by cleavage with the restriction enzymes BamHI, EcoRI, HindII, and HaeIII. A 32P-labeled probe hybridized to Hind fragments A, B, and C of HPV 1 DNA. A serological relationship to HPV 1 could be demonstrated by using a rabbit antiserum against SDS-disrupted HPV 1.

Bei einem 24jahrigen Neger aus Ober-Volta fand sich eine generalisierte Aussaat Verruca-plana-artiger Effloreszenzen (Abb. 1) mit Pityriasis-versicolor-alba-ahnlichen Lasionen am Stamm. Beginn im 1. Lebensjahr mit einem flachen Herd an der linken Schlafe. Eltern und vier Geschwister angeblich hautgesund.

Persisting human papilloma virus (HPV) 2 induced common warts of a chronic lymphatic leukemia patient were orally treated with aromatic retinoid Ro 10-9359 (Tigason®). Clinically, the lesions improved rapidly. Virus-specific cytopathogenic effects (CPE), virus particles and viral DNA were no longer detectable. Therapy was discontinued because of the development of a liposarcoma, which led to a complete relapse of the cutaneous lesions. HPV-2 specific parameters, CPE and viral DNA, were restored. Comparison of the restriction enzyme cleavage patterns revealed that warts before and after therapy contained the same HPV-2 subtype. The implications of the observation on the effect of Tigason® on virus-induced papillomas are discussed, liposarcoma

At least two groups of human papilloma viruses can be distinguished serologically: on the one hand HPV 1-3, which are closely related but differ in the restriction enzyme pattern of their DNA, and on the other hand HPV-4. The age distributions of patients with warts induced by HPV 1-3 or by HPV-4, respectively, differ markedly. HPV 1-3 predominates between 5 and 15 years of age, whereas HPV-4 could be isolated more often between the ages of 20-25 years. The large number of HPV-1-3-induced warts in children is paralleled by a high percentage of HPV-1 antibody-positive sera in the same age group (about 50%). With increasing age the percentage of HPV-1 antibody-positive sera decline gradually. This pattern of seroreactivity was compared to that of patients with various papillomas and with several malignant tumors. There is no evidence to suggest a link between HPV 1-3 and condylomata acuminata, laryngeal papillomas or any of the malignant tumors tested.

A case of epidermodysplasia verruciformis in a patient from Upper-Volta is described. Slightly elevated, flat warts were observed on hands, feet, arms and legs, and pityriasis versicolor-like lesions were found mainly on the trunk. The patient showed no malignant tumors. Histological examination revealed hyperkeratosis, granulosis and moderate acanthosis with large, foamy, basophilic keratinocytes in stratum granulosum and stratum spinosum. Papillomavirus particles could be prepared from these lesions and were differentiated from known papillomavirus types by immune electron microscopy with monospecific antisera and by DNA-DNA hybridization. The viral DNA was characterized by cleavage with several restriction endonucleases and a physical map of the resulting fragments was established. The virus is designated as HPV 8. Preliminary seroepidemiologic studies with human sera indicate a rather wide distribution of HPV 8. Blot hybridization of DNA from human carcinomas with 32P-labelled virus DNA detected no HPV 8-specific sequences.

Papillomaviruses do not replicate in tissue culture. Most viral DNAs were therefore directly cloned from biopsy material and characterized by hybridization to known reference DNAs, and by sequencing. There seems to be only one sense strand. The genome can be subdivided into a 0.4 – 1 kb regulatory region (origin of replication, enhancer and promoter elements), an early region, comprising about 4 kb, and a late region, consisting of 3 kb. At least 42 human papillomavirus (HPV) types are differentiated on the basis of less than 50% crosshybridization. They show various degrees of homology among each other, sometimes in different areas of the genome. The viral DNA usually persists extrachromosomally in tumor cells. Only with HPV16 and 18 integration was consistently, observed when tumors became malignant. In transformed cells there are rather low levels of viral transcripts, although an active enhancer in front of the early transcription unit is stimulated by a trans-activating viral protein. These positive regulatory signals are counteracted by negative control elements. So far, there is no evidence that activation of cellular oncogenes is required for transformation by papillomaviruses.

Papillomavirus-specific transcription was investigated in the absence of virus particle production in BPV 1-induced hamster tumors. The analysis revealed a single virus-specific polyadenylated transcript of 1300-base length, which was mapped on the genome of BPV 1. Hybridization with 32P-labeled probes confined the transcribed region to two HpaII fragments, which are adjacent to the BamHI cleavage site within the 1.4 × 106 dalton BamHI/EcoRI fragment. Related DNA sequences could be detected within the genomes of HPV 1 HPV 4 using relaxed hybridization conditions.

The human papillomaviruses (HPVs) cause a variety of benign tumors of the skin and mucosa and are of particular medical interest due to their association with human cancers (Pfister 1984). A large group of HPVs is associated with epidermodysplasia verruciformis (ev), a lifelong disease, which is characterized by disseminated flat warts and macular skin lesions that develop into squamous cell carcinomas in 30%-50% of the sufferers (Orth 1987). More than 90% of these cancers are persistently infected with HPV-5 or HPV-8, which were also discovered in skin carcinomas of immunosuppressed transplant recipients (Bunney et al. 1987). These HPV types are therefore assumed to represent particular risk factors for the development of skin cancer.

Summary Human papillomaviruses (HPVs) 5, 8, 19 and 25 induce macular skin lesions in patients with epidermodysplasia verruciformis. HPVs 5 and 8 are known to prevail in skin carcinomas, which develop in about one-third of these patients. We compared the viral DNAs by heteroduplex analysis and on the basis of partial nucleotide sequences. The colinear genomes were closely related and showed nucleotide sequence homology in the range of 40% to 90%. Homology values between 70% and 80% were observed throughout roughly 4 kb of the heteroduplex molecules as estimated after ‘calibration’ by partial sequencing. Heteroduplex analysis did not support the hypothesis that the different HPV types arise by recombination and allowed no grouping to correlate with the association with malignant tumours. The upstream regulatory sequences of HPVs 8, 19 and 25 appeared highly conserved but differed from those of previously sequenced papillomaviruses in length, in the TATA motif, in the copy numbers and positions of the ACCGN4CGGT palindrome and of a YGCCAA direct repeat, and in two strictly conserved blocks of 33 and 29 nucleotides.

Disease: Skin warts, anogenital warts (condyloma acuminatum, cervical intraepithelial neoplasia, bowenoid papulosis), oral and laryngeal papillomas, conjunctival papillo-mas, focal epithelial hyperplasia Heck; anogenital cancer, laryngeal carcinomas, tongue carcinomas, skin carcinomas of patients with epidermodysplasia verruci-formis.

SUMMARY A variety of HPV types infect the anogenital mucosa, giving rise to lesions that differ in clinical appearance, histology, and their risk of malignant progression. HPV-16 is distinguished by a strong association with high-grade intraepithelial neoplasia and the greatest prevalence in anogenital malignancy. Most cancers appear to have a multifactorial etiology, and HPV infection alone is probably insufficient for malignant transformation. However, the consistent association between HPV infection and anogenital cancers emphasizes that the sexually transmitted papillomaviruses may have a necessary role in carcinogenesis. Hence, there is a prospect that vaccination programs may one day allow public health control of HPV infection, thereby eliminating an important risk factor.

Bovine and human sera were analyzed for the presence of antibodies against bovine papillomavirus types 1 and 2 (BPV 1 and 2) and human papillomavirus type 1 (HPV 1) in a solid-phase radioimmunoassay. Human sera did not react with BPV antigens, and bovine sera showed no evidence of antibodies against HPV 1. In contrast, 19% of all bovine sera tested reacted with BPV 1 and 2 antigens, and 35% of human sera revealed antibodies against HPV 1. No serologic evidence was obtained for heterologous infections of persons exposed preferentially to cattle (farmers, butchers, and patients with Q-fever).

Publisher Summary Papillomaviruses are clearly proven to be the etiologic agents of anogenital lesions, with the potential to progress to squamous cell carcinomas. Viral particles, DNA, and/or capsid antigens can be demonstrated in benign precursors and the proliferations can be transmitted from person to person by cell-free extracts. The complete nucleotide sequences of Human Papillomaviruses (HPVs)—namely, HPV 6, HPV 11, and HPV 16—revealed the familiar genome organization of papillomaviruses and homologous sequences to those open reading frames that were shown to code for transforming functions in the case of BPV1. Malignant conversion of papillomavirus-induced tumors is well established for a number of animal systems and for the human disease epidennodysplasia verruciformis. HPV DNA persists in genital carcinomas either integrated into the host genome or extrachromosomally and is transcribed at least in some tumors. The worldwide prevalence of HPV 16 is noteworthy and may possibly indicate an increased cancerogenic potential of this virus. A tentative calculation indicates that the cancer risk after HPV infection equals or exceeds the risk attended with the infections by other human tumor viruses such as HTLVI, Epstein-Barr virus, or hepatitis B virus. Tumor progression is certainly subjected to additional factors such as chemical or physical carcinogens, hormones, and systemic or local immune deficiencies. The molecular biology of HPV infection has to be further examined to learn more about the viral role in keratinocyte transformation, which will be essential to define relevant diagnostic probes and possible candidates for therapeutic intervention.

BPV 1-induced hamster tumors were used as model system to investigate the state of viral DNA in non-virus-producing tumors arising from papillomavirus infection. DNAs from a fibroma and three fibrosarcomas were analyzed for BPV 1 DNA by the Southern blot technique. The vast majority of viral DNA persists in a nonintegrated form, since: (i) supercoiled BPV-DNA can be purified by CsCl-ethidium bromide equilibrium centrifugation, (ii) restriction endonucleases, which do not cut viral DNA, do not change the DNA pattern in comparison to uncleaved samples, and (iii) digests of BPV-DNA with restriction enzymes Hpa I, Hpa II, and Hha I, respectively, lead to identical patterns with DNA from hamster tumors and from warts. Less than one genome equivalent per cell could persist in an integrated form. Virus-specific, high-molecular-weight DNA in the tumors may be interpreted as oligomeric or catenated DNA. Cleavage analysis of tumor DNA with the restriction enzymes Hpa II and Hha I, both sensitive to DNA methylation, provided no evidence for methylation of BPV 1 DNA in hamster tumors.

The serological characterization of virus isolates from verrucae vulgares and plantar warts revealed that HPV 1 and HPV 4 are present in about 50% of these warts with HPV 1 being more prevalent, especially in plantar warts. Parallel to the high incidence of HPV 1 infections, about 50% of non-selected young adults contained antibodies against HPV 1. Only HPV 4 particles, however, reacted with serum from a patient with epidermodysplasia verruciformis when tested by immuno-electron microscopy. An examination of HPV 1 proteins indicated that the major structural proteins VP2 and VP3 are trypsin sensitive. Tryptic degradation leads to distinct polypeptides with molecular weights between 37,000 and 23,000 which may be correlated to minor protein components of HPV 1 preparations. HPV 1 histone-like proteins, which co-migrate with purified cellular histones in SDS gel electrophoresis were analyzed in an acetic acid urea system. It was shown that H3- and H4-like proteins differ from cellular histones. The reason for this difference and its meaning are discussed.

Human papillomavirus (HPV) 6 usually induces tumors of the genital, oral, or laryngeal mucosa. An HPV 6-related DNA of 8.2 kb was detected in an extrachromosomal state in atypically located condylomas of the mamilla and was molecularly cloned. The identity of the cloned HPV DNA and the viral DNA in the biopsy was confirmed by comparative Pst l cleavage analysis, which showed typical HPV 6 DNA fragment patterns except for 0.2-kb larger B fragments. Sequencing revealed an exact 236-bp duplication encompassing nucleotides 7681 to 7896 of HPV 6b. This tandem repeat is just upstream from the putative early promoter and contains a 20-bp insertion at position 7720, which constitutes an enhancer element described by R. F. Rando, W. D. Lancaster, P. Han, and C. Lopez ( Virology 155, 545–556, 1986). A Hin fl- Pst l fragment containing the whole duplication was cloned into an enhancer-dependent CAT expression vector and led to three- to sevenfold increased CAT activity when compared with the monomeric sequence in C127 cells and BPV1 transformed C127 cells. This indicates that the duplication within the HPV 6 isolate from the mamilla may influence early gene expression and possibly tissue tropism.

Soluble tumour necrosis factor receptors type I and II (sTNF-RI and II) were evaluated in sera from patients with epidermodysplasia verruciformis and patients with cutaneous warts, actinic keratoses, squamous cell carcinomas or basal cell carcinomas by specific enzyme-linked immunobiological assays. In patients with widespread epidermodysplasia verruciformis lesions, the levels of both sTNF-Rs were in normal range. Both types of sTNF-Rs were significantly increased in patients with warts. The levels of sTNF-RI were significantly increased in patients with multiple actinic keratoses, squamous cell carcinoma and basal cell carcinoma. Increased levels of circulating sTNF-Rs may facilitate development of cutaneous tumours. Normal levels of sTNF-Rs in patients with epidermodysplasia verruciformis might, at least partially, contribute to a slow growth and low metastatic potential of cancers in these patients.

At least 45 different human papillomavirus (HPV) types are presently known, which induce epithelial tumors of the skin or mucosa. 1 The majority of the warts, papillomas, leukoplakias, or hyperplasias are benign, but some lesions, particularly dysplasias of the cervix uteri, macules of patients with epidermodysplasia verruciformis (EV), and laryngeal papillomas in adults, may progress to squamous cell carcinomas. Infection by HPV elicits humoral and cellular immune mechanisms against virus particles and tumor tissue, 2,3 which trigger tumor regression and leave the host immune to reinfection. The incidence of some HPV types appears rather unaffected by the immune status of the patient, while susceptibility to other types depends more or less on an impaired immune system. Infections by HPV 2, 3, 4, and 10, for example, are considerably favored by a compromised immune system, which is reflected by the frequent occurrence in immunosuppressed allograft recipients. 4-6