Toshihiko Matsukura

Both episomal and integrated forms of human papillomavirus type 16 are involved in invasive cervical cancers

The form of human papillomavirus type 16 (HPV 16)DNA in specimens of invasive cervical cancer was investigated. High molecular, tandem repeats of viral sequences were detected as several distinct bands, using a low concentration (0.5%) agarose gel and a no-cut enzyme (HindIII) for HPV 16. Two-dimensional agarose gel electrophoresis allowed us to differentiate between the episomal multimeric and the integrated forms of viral DNA. All 34 cervical cancer specimens showed the characteristic PstI cleavage pattern of HPV 16 DNA, indicating that a full viral genome was present in these specimens, and 24 specimens (70%) showed only episomal monomeric or multimeric forms without the integrated form of HPV 16 DNA. The remaining 10 specimens (30%) showed integrated multimeric forms of viral DNA, either without the episomal form (8 specimens) or with the concomitant episomal form (2 specimens). In addition, a metastatic tumor in a pelvic lymph node showed only the episomal form of viral DNA, whereas its primary cervical cancer showed both episomal and integrated forms of viral DNA. There was no correlation between the forms of viral DNA and the clinical stages of tumors. The result indicates that both episomal and integrated forms of a complete HPV 16 DNA are involved in invasive cervical cancers.

The presence of mucosal human papillomavirus in Bowen's disease of the hands

Bowens disease (BD) of the genital skin region is generally associated with human papillomavirus (HPV) infection. Various molecular analyses have identified mainly HPV‐16 in the lesions. However, the HPV genotypes associated with BD of the hands have not yet been characterized.

Distinct manifestations of human papillomaviruses in the vagina

To clarify the pathogenic relationships between human papillomavirus (HPV) and vaginal intraepithelial neoplasia (VAIN), we examined 71 vaginal biopsy specimens by histopathology and immunohistochemistry and analyzed the presence of HPV DNA by blot hybridization at Tm − 40°C using an HPV 58 probe (PBM‐58 method). We found 27 cases of VAIN in patients with previous hysterectomy or antecedent or concomitant cervical intraepithelial neoplasia (CIN) and 44 cases of VAIN in patients without any abnormal findings on the cervix and the vulva. Histopathologically, 53 of 71 cases were graded as VAIN I and 15 and 3 cases were VAIN II and III, respectively, while 59 cases showed positivity for HPV capsid antigen by immunohistochemistry. Using the PBM‐58 method, all 71 VAIN cases harbored a single HPV type at more than 1,000 viral copies per cell. We identified 15 different types (HPV 16, 18, 30, 31, 35, 40, 42, 43, 51, 52, 53, 54, 56, 58 and 66). Furthermore, we molecularly cloned 7 novel prototypes (HPV 59, 61, 62, 64, 67, 69 and 71) from VAIN I. Our results are strongly indicative that HPVs are etiologic agents of VAIN, like in the case of CIN. The distinct manifestations of HPV infection in the vagina are discussed in comparison with those in the cervix. Int. J. Cancer 72:412–415, 1997.

Molecular cloning of a novel human papillomarvirus (type 58) from an invasive cervical carcinoma

A novel human papillomavirus type (HPV) was cloned from an invasive cervical carcinoma. The viral clone showed no homology with other known prototypes of HPV (HPV-1 through HPV-57), except HPV-33 by Southern blot analysis under stringent conditions. It showed less than 20% homology to HPV-33 by reassociation kinetic analysis. The restriction endonuclease map of the clone was different from those of other HPV types and its predicted genome organization surmised by hybridization with subgenomic fragment probes of HPV-33 DNA showed the typical HPV genome organization. The results indicate that this clone is a new type of HPV, designated as HPV-58, distinct from the other known types of HPV. HPV-58 was detected in none of 6 specimens of cervical condylomata acuminata, in 7 of 58 specimens of cervical intraepithelial neoplasia, and in 4 of 50 specimens of invasive cervical carcinoma studied in Nagano prefecture, Japan.

Human papillomavirus type 58 DNA sequence

The complete nucleotide sequence of human papillomavirus type 58 (HPV 58) DNA cloned from an invasive cervical carcinoma was determined. The HPV 58 genome consists of 7824 nucleotides, containing 37.9% of GC residues, and has a similar genome organization of other HPVs. On the nucleotide sequence level, it conserves the signal sequences for regulation of gene expression as with other genital HPVs and exhibits an extensive homology with HPV 33 (77%). Comparative analysis of amino acid sequences reveals that HPV 58 is closely related with HPVs 16, 31, and 33, and is more distantly related with HPVs 6, 11, 18, and 39. HPVs 58, 16, 31, and 33 can be regarded as a group in HPV.

NUCLEOTIDE SEQUENCE AND PHYLOGENETIC CLASSIFICATION OF HUMAN PAPILLOMAVIRUS TYPE 67

The complete nucleotide sequence of human papillomavirus type 67 (HPV 67) cloned from a vaginal intraepithelial neoplasia, has been determined. It consists of 7801 nucleotides with a GC content of 38.4% and exhibits similar genome organizations of genital HPVs. By phylogenetic analysis based on the full nucleotide sequences of E6 open reading frame of 28 genital HPVs, HPV 67 was clustered with HPV 16, 31, 33, 34, 35, 52, and 58.

Detection of Human Papillomavirus Type 58 in Polydactylous Bowen’s Disease on the Fingers and Toes of a Woman – Concurrent Occurrence of Invasive Vulval and Cervical Carcinomas

The group related to human papillomavirus (HPV) type 16 (HPV-16, -31, -33, -35, -52, -58 and -67) is dominantly identified in cervical intraepithelial neoplasia and cervical carcinomas. HPV-16 has also been frequently detected in Bowen’s disease on the hands and feet. We describe herein a case of polydactylous Bowen’s disease on the fingers and toes of a woman who had had radical vulvectomy and hysterectomy for concomitant invasive vulval and cervical carcinomas. All the lesions, except for the lesions on the periungual side of her left index, middle and ring fingers, harbored HPV-58 DNA with more than 100 entire viral genome copies per cell detected by Southern blot hybridization. The histological localization of the viral DNA was confirmed in all the lesions by in situ hybridization. We could also retrospectively demonstrate HPV-58 DNA in her invasive vulval and cervical carcinoma tissues.

Global Genomic Diversity of Human Papillomavirus 11 Based on 433 Isolates and 78 Complete Genome Sequences

ABSTRACT Human papillomavirus type 6 (HPV6) is the major etiological agent of anogenital warts and laryngeal papillomas and has been included in both the quadrivalent and nonavalent prophylactic HPV vaccines. This study investigated the global genomic diversity of HPV6, using 724 isolates and 190 complete genomes from six continents, and the association of HPV6 genomic variants with geographical location, anatomical site of infection/disease, and gender. Initially, a 2,800-bp E5a-E5b-L1-LCR fragment was sequenced from 492/530 (92.8%) HPV6-positive samples collected for this study. Among them, 130 exhibited at least one single nucleotide polymorphism (SNP), indel, or amino acid change in the E5a-E5b-L1-LCR fragment and were sequenced in full. A global alignment and maximum likelihood tree of 190 complete HPV6 genomes (130 fully sequenced in this study and 60 obtained from sequence repositories) revealed two variant lineages, A and B, and five B sublineages: B1, B2, B3, B4, and B5. HPV6 (sub)lineage-specific SNPs and a 960-bp representative region for whole-genome-based phylogenetic clustering within the L2 open reading frame were identified. Multivariate logistic regression analysis revealed that lineage B predominated globally. Sublineage B3 was more common in Africa and North and South America, and lineage A was more common in Asia. Sublineages B1 and B3 were associated with anogenital infections, indicating a potential lesion-specific predilection of some HPV6 sublineages. Females had higher odds for infection with sublineage B3 than males. In conclusion, a global HPV6 phylogenetic analysis revealed the existence of two variant lineages and five sublineages, showing some degree of ethnogeographic, gender, and/or disease predilection in their distribution. IMPORTANCE This study established the largest database of globally circulating HPV6 genomic variants and contributed a total of 130 new, complete HPV6 genome sequences to available sequence repositories. Two HPV6 variant lineages and five sublineages were identified and showed some degree of association with geographical location, anatomical site of infection/disease, and/or gender. We additionally identified several HPV6 lineage- and sublineage-specific SNPs to facilitate the identification of HPV6 variants and determined a representative region within the L2 gene that is suitable for HPV6 whole-genome-based phylogenetic analysis. This study complements and significantly expands the current knowledge of HPV6 genetic diversity and forms a comprehensive basis for future epidemiological, evolutionary, functional, pathogenicity, vaccination, and molecular assay development studies.

Human papillomavirus type 58 in Bowen's disease of the elbow

Human papillomavirus (HPV) can be detected in skin lesions of Bowens disease, particularly on the fingers, and its genotype is associated with mucosal/genital types of HPV. We report herein an 85‐year‐old woman who had HPV‐associated Bowens disease on her elbow. HPV‐58 DNA was detected in the lesion by polymerase chain reaction with restriction fragment length polymorphism and by Southern blot hybridization. In situ hybridization revealed numerous hybrid cells in the nuclei of the upper epidermis and stratum corneum of Bowens disease. A high‐risk type of mucosal HPV‐58 DNA is associated with Bowens disease in this case, suggesting that HPV‐related Bowens disease is not always restricted to genital or finger lesions.

Human herpesvirus 8 DNA is rarely found in Bowen's disease of non‐immunosuppressed patients

1 Barth IH. Layton AM. Cunliffe WJ. Endocrine factors in prctind postmenopausii! women with hidradenitis suppunitiva. Hr j Derimitol 1996: 154: 1057-9. 2 Mortimer P.S. Dawber RPR, Gal(.-,s MA. .Modrc RA. A diiuhle-hliiid controlled cross-over trial of cyprott-rone acetate in females with hidriidcnitis supptiraliva. Br / Dcniuilo! 198f); 115: 2(i5-S. J Miller )A. Woiriiiniwskii FT. Dowd PM el at. AntUitidrogen treatmcnl in women with acne: a conlrollfLi trial. Hr I Iknimlol 19S(i: 1 14: 705-1 (v 4 Kligman AM. P()stmeni)p;uisal arne, Ciilis 1441; 47: 425-6.