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Molecular cloning and nucleotide sequence analysis of a novel human papillomavirus (Type 82) associated with vaginal intraepithelial neoplasia.

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.

SUBMITTER: Kino N

PROVIDER: S-EPMC95829 | biostudies-literature | 2000 Jan

REPOSITORIES: biostudies-literature

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Molecular cloning and nucleotide sequence analysis of a novel human papillomavirus (Type 82) associated with vaginal intraepithelial neoplasia.

Kino N N Sata T T Sato Y Y Sugase M M Matsukura T T

Clinical and diagnostic laboratory immunology 20000101 1

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 nucleotid ...[more]

PMID: 10618284

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Project description:IntroductionVaginal intraepithelial neoplasia (VAIN) is a pre-malignant lesion, potentially leading to vaginal cancer. It is a rare disease, representing less than 1% of all intraepithelial neoplasia of the female genital tract. Similar to cervical intraepithelial neoplasia (CIN), there are three different grades of VAIN. VAIN 1 is also known as a low-grade squamous intraepithelial lesion (LSIL), whereas VAIN 2 and VAIN 3 both represent high-grade squamous intraepithelial lesions (HSIL). Risk factors for the development of VAIN are similar to those for cervical neoplasia, i.e. promiscuity, starting sexual activity at an early age, tobacco consumption and infection with human papillomavirus (HPV). However, compared to other intraepithelial neoplasia such as CIN or VIN (vulvar intraepithelial neoplasia), there still is little understanding about the natural course of VAIN and its capacity for pro- or regression. Furthermore, there is controversial data about the HPV detection rate in VAIN lesions.Patients and methods67 patients with histologically confirmed VAIN, who were diagnosed between 2003 and 2011 at the University Women´s Hospital of Heidelberg Germany, were included in this study. The biopsies of all participating patients were subjected to HPV genotyping. GP-E6/E7 Nested Multiplex PCR (NMPCR) was used to identify and genotype HPV. Eighteen pairs of type-specific nested PCR primers were assessed to detect the following "high-risk" HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68, as well as the "low-risk" genotypes 6/11, 42, 43 and 44. The data was analyzed with the software SAS (Statistical Analysis System).ResultsAll 67 cases were eligible for DNA analysis. The median age was 53 years. The largest group with 53% (n = 36) was formed by women, who were first diagnosed with VAIN between the age of 41 to 60 years. 50% (n = 37) of the patients presented a VAIN in the upper 1/3 of the vagina. 58 (87%) were diagnosed with HSIL (VAIN). The median age in patients with LSIL (VAIN) was 53 years and in patients with HSIL (VAIN) 53.5 years. 12 women (18%) had an immunosuppression. HPV positivity was confirmed in 37 patients (55%). Except for a single patient, who had a triple infection with HPV types 6/11, 16 and 68, only infections with one single HPV genotype were detected. An infection with the HPV genotypes 31, 39, 45, 51, 58, 59, 66, 42, 43 and 44 couldn't be found in any of the patients. In 28 patients with diagnosed VAIN, an infection with HPV 16 could be shown, 24 (86%) of them were diagnosed with a HSIL (VAIN). 16 (24%) women presented condylomata and 13 of them (81%) had a positive HPV status. However, only 47% of the women without condylomata presented a positive HPV status, resulting in a significant correlation (p = 0.0164) between condylomata and HPV infection. In 28 of all 67 patients (42%), recurrence of the neoplasia occurred.ConclusionHPV 16 is the main virus-type to be associated with the development of a VAIN. Also, HPV 16 infection, VIN or condylomata acuminata in the past medical history seemed to be significant factors for early relapse.

Project description:BACKGROUND:In this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts. METHODS:The vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n?=?78), women with low-grade squamous intraepithelial lesions (LSIL, n?=?51), women with high-grade squamous intraepithelial lesions (HSIL, n?=?23), women with invasive cervical cancer (Cancer, n?=?9) and healthy women without HPV infection (Normal, n?=?68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. RESULTS:HPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs. CONCLUSIONS:This work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

Project description:ObjectivesTo evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).DesignData from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up.SettingPrimary care centres and university or hospital associated health centres in 24 countries and territories around the world.Participants17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy.InterventionThree doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6.Main outcome measuresVaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied.ResultsIn the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma.ConclusionsQuadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up.Trial registrationsNCT00092521 and NCT00092534.

Dataset Information

Molecular cloning and nucleotide sequence analysis of a novel human papillomavirus (Type 82) associated with vaginal intraepithelial neoplasia.

Publications

Molecular cloning and nucleotide sequence analysis of a novel human papillomavirus (Type 82) associated with vaginal intraepithelial neoplasia.

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