Abstract

The genome of a novel human papillomavirus (HPV-82) was cloned from a vaginal intraepithelial neoplasia grade I. In our series of 291 biopsy specimens, HPV-82 was identified in one case each of cervical intraepithelial neoplasia grade II and grade III by blot hybridization. The histological localization of HPV-82 DNA in the three lesions was confirmed by in situ hybridization. The results indicated that HPV-82 is an etiologic agent for vaginal and cervical intraepithelial neoplasia. By nucleotide sequence similarity of L1 open reading frame (ORF), HPV-82 was closely related to HPV-26, -51, and -69. To know the precise relationship between the HPVs, we determined the complete sequence of HPV-82, as well as that of HPV-69. Sequencing revealed that the four HPVs had no initiation codon in the E5 ORF and had extensive nucleotide sequence similarities in all ORFs. In addition, they exhibited unique frame position patterns for ORFs, different from those of the other genital HPVs.

Highlights

  • Human papillomavirus (HPV) has a genome of closed-circular double-stranded DNA and HPV type 1 (HPV-1), HPV-2, and HPV-4 were first molecularly cloned in 1980 [6]

  • A lesion showing sharply demarcated white epithelium was biopsied (Fig. 1a). It was histopathologically diagnosed as vaginal intraepithelial neoplasia (VAIN) grade I (Fig. 1b), and HPV capsid antigen was detected within the nuclei of the superficial koilocytotic cells by immunohistochemistry (Fig. 1c)

  • We determined partial sequences of the cloned DNA, corresponding to the L1 open reading frame (ORF) of HPV, which showed less than 90% nucleotide sequence identity to L1 sequences of any known HPVs at that time

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Summary

Introduction

Human papillomavirus (HPV) has a genome of closed-circular double-stranded DNA and HPV type 1 (HPV-1), HPV-2, and HPV-4 were first molecularly cloned in 1980 [6]. Genital HPVs are pathologically classified into two groups, high-risk types associated with malignant tumors and low-risk types associated with benign tumors. All 39 genital HPVs were not yet rationally classified in these groups, and HPVs designated as high-risk types were different from study to study [5, 7, 8, 15]. Enough, HPV-66, classified as a high-risk type in the former study, was considered a low-risk type in the latter. It was not known how each HPV was classified in these studies. We speculated that any HPV detected in invasive cervical carcinoma (ICC) might be categorized as a high-risk type [1]. We examined the histopathologic localization of the viral DNA in different genital lesions

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